Population-based cohort study to investigate the changes in prevalence, severity profile, and treatment modalities used in Korean atopic dermatitis patients.

In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0-1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1-11-year-old group. Conversely, the 12-19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease.

X-linked inhibitor of apoptosis protein (XIAP) deficiency causes refractory inflammatory bowel disease. The XIAP protein plays a pivotal role in the pro-inflammatory response through the nucleotide-binding oligomerization domain-containing signaling pathway that is important in mucosal homeostasis. We analyzed the molecular mechanism of non-synonymous pathogenic variants (PVs) of XIAP BIR2 domain. We generated N-terminally green fluorescent protein-tagged XIAP constructs of representative non-synonymous PVs. Co-immunoprecipitation and fluorescence cross-correlation spectroscopy showed that wild-type XIAP and RIP2 preferentially interacted in live cells, whereas all non-synonymous PV XIAPs failed to interact properly with RIP2. Structural analysis showed that various structural changes by mutations, such as hydrophobic core collapse, Zn-finger loss, and spatial rearrangement, destabilized the two loop structures (174-182 and 205-215) that critically interact with RIP2. Subsequently, it caused a failure of RIP2 ubiquitination and loss of protein deficiency by the auto-ubiquitination of all XIAP mutants. These findings could enhance our understanding of the role of XIAP mutations in XIAP-deficient inflammatory bowel disease and may benefit future therapeutic strategies.

Hormone Replacement Therapy and Psoriasis Risk: A Nationwide Population-Based Cohort Study.

BACKGROUND: Hormone replacement therapy (HRT) is used to relieve menopause symptoms, but has been reported to be associated with coronary heart disease and cancers in women. However, a link between HRT and psoriasis has yet to be established. The aim of this study was to determine the association between HRT and the risk of psoriasis. METHODS: We executed a nationwide population-based study. A total of 1,130,741 post-menopause women were enrolled in the national health care insurance database based on the enrollment criteria. The study population was classified into four groups based on the duration of the HRT, and the risk of psoriasis was analyzed. RESULTS: The incidence rates of psoriasis per 1,000 person-years were 3.36 and 4.09 in the no history of HRT and ≥ 5 years of HRT, respectively. After adjustment for age, smoking, alcohol intake, regular exercise, body mass index, diabetes mellitus, hypertension, and dyslipidemia, the most prolonged duration of the HRT group (≥ 5 years) exhibited significantly increased risk of developing psoriasis (hazard ratio, 1.22; 95% confidence interval, 1.16-1.29). CONCLUSION: We propose that HRT in post-menopausal women is associated with an increased likelihood of psoriasis development.

Increased Risk of Renal Malignancy in Patients with Moderate to Severe Atopic Dermatitis.

BACKGROUND: Evidence for an association between atopic dermatitis (AD) and cancer is still insufficient. In particular, the association between the risk of renal malignancy and the severity of AD has not been thoroughly investigated. OBJECTIVE: To investigate the risk of renal malignancy and determine the association between AD severity and cancer risk using data from the Korean National Health Insurance Service (KNHIS) database. METHODS: We performed a population-based cohort study using the National Health Claims database from the NHIS in Korea. RESULTS: We found a statistically significant association between AD and overall malignancy (for mild AD, hazard ratio (HR): 1.061, 95% confidence interval (CI): 1.006-1.118; for moderate to severe AD, HR: 1.061, 95% CI: 1.014-1.11) compared with the no AD group. The moderate to severe AD group showed a significantly increased risk for renal malignancy (adjusted HR: 1.533, 95% CI: 1.209-1.944) compared with the no AD group. LIMITATIONS: Patient inclusion is solely based on diagnostic codes. We had no data about drug use, genetic factors, or other medical history that could affect the cancer risk. CONCLUSION: In our large population-based cohort study, moderate to severe AD was associated with increased risk of renal malignancy. Regular check-ups for renal malignancy are recommended in this population.

Schisandrin B protects boar spermatozoa against oxidative damage and increases their fertilization ability during in vitro storage.

Oxidative stress due to low temperatures during in vitro preservation reduces boar spermatozoa quality. It has been proven that Schisandrin B (Sch-B) can act against oxidative stress in cells. Therefore, the purpose of this study was to investigate whether the treatment with Sch-B could improve the quality of boar sperm during storage at 17 °C. Semen samples were randomly divided into four groups and added to the Beltsville Thawing Solution containing different concentrations of Sch-B (0, 0.1, 0.5, and 1 mg/L) after collection. Each group was then preserved at 17 °C and the sperm motility, membrane integrity, and acrosome integrity were detected to determine the maximum available concentration of Sch-B for sperm. The optimal concentration was set at 0.1 mg/L and was used in subsequent experiments. Sperms treated with 0 and 0.1 mg/L Sch-B were evaluated for lipid peroxidation (MDA) and fertilization ability through in vitro fertilization. Finally, the quality of blastocysts which were formed by 0 and 0.1 mg/L Sch-B-treated sperm was determined. The results showed that compared with the control, the addition of 0.1 mg/L Sch-B improved boar sperm motility, and the addition of 0.1 and 0.5 mg/L Sch-B improved sperm membrane integrity and acrosome integrity. Treatment with 0.1 mg/L Sch-B reduced the level of MDA and increased the cleavage rate, blastocyst rate, and total cell number of blastocysts compared to the rate and number in the control group. However, no significant difference was observed in the ROS levels of blastocysts between the treatment and the control groups. The expression levels of CAT, SOD2, and Bcl-2 in IVF-blastocysts formed using sperm stored for one day at 17 °C were significantly higher than those in the control blastocysts. On day 4 of storage, CAT and Bcl-2 expression were significantly higher in IVF-blastocysts formed from sperm treated with 0.1 mg/L Sch-B than that in the control blastocysts. The ratio of Bax/Bcl-2 was also significantly higher in IVF-blastocysts formed using Sch-B-treated sperm. Our findings demonstrate that treatment with Sch-B can protect boar sperm from oxidative stress during liquid preservation and can increase the fertilization ability of the sperm.

Effective hexanol production from carbon monoxide using extractive fermentation with Clostridium carboxidivorans P7.

This study achieved high production of hexanol via gas fermentation using Clostridium carboxidivorans P7 by extracting hexanol from the fermentation broth. The hexanol extraction efficiency and inhibitory effects on C. carboxidivorans P7 of 2-butyl-1-octanol, hexyl hexanoate and oleyl alcohol were examined, and oleyl alcohol was selected as the extraction solvent. Oleyl alcohol was added at the beginning of fermentation and during fermentation or a small volume of oleyl alcohol was repeatedly added during fermentation. The addition of a small volume of oleyl alcohol during fermentation was the most effective for CO consumption and hexanol production (5.06 g/L), yielding the highest known hexanol titer through any type of fermentation including gas fermentation. Hexanol production was further enhanced to 8.45 g/L with the repeated addition of oleyl alcohol and ethanol during gas fermentation. The results of this study will enable sustainable and carbon-neutral hexanol production via gas fermentation.

Correction: Altered Cell Cycle Gene Expression and Apoptosis in Post-Implantation Dog Parthenotes.

[This corrects the article DOI: 10.1371/journal.pone.0041256.].

Prime editor-mediated correction of a pathogenic mutation in purebred dogs.

Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

Effect of Passage Number of Conditioned Medium Collected from Equine Amniotic Fluid Mesenchymal Stem Cells: Porcine Oocyte Maturation and Embryo Development.

Oocyte in vitro maturation (IVM) is the most important first step in in vitro embryo production. One prerequisite for the success of IVM in oocytes is to provide a rich culture microenvironment that meets the nutritional needs of developing oocytes. We applied different equine amniotic fluid mesenchymal stem cell conditioned medium (eAFMSC-CM) from passages 7, 18, and 27 to porcine oocytes during IVM to determine its effects on oocyte development and subsequent embryo development, specifically. The eAFMSC-CM from passage 7 (eAFMSC-CMp7) has a considerable impact on 9 genes: BAX, BCL2, SOD2, NRF2, TNFAIP6, PTGS2, HAS2, Cx37, and Cx43, which are associated with cumulus cell mediated oocyte maturation. GSH levels and distribution of mitochondrial and cortical granules were significantly increased in oocytes incubated with eAFMSC-CMp7. In addition, catalase and superoxide dismutase activities were high after IVM 44 h with eAFMSC-CMp7. After in vitro fertilization, blastocyst quality was significantly increased in the eAFMSC-CMp7 group compared to control. Lastly, the antioxidant effect of eAFMSC-CMp7 substantially regulated the expression of apoptosis, pluripotency related genes and decreased autophagy activity in blastocysts. Taken together, this study demonstrated that the eAFMSC-CMp7 enhanced the cytoplasmic maturation of oocytes and subsequent embryonic development by generating high antioxidant activity.

Production of Hexanol as the Main Product Through Syngas Fermentation by Clostridium carboxidivorans P7.

The production of hexanol from syngas by acetogens has gained attention as a replacement for petroleum-derived hexanol, which is widely used in the chemical synthesis and plastic industries. However, acetogenic bacteria generally produce C2 compounds (e.g., acetate and ethanol) as the main products. In this study, the gas fermentation conditions favorable for hexanol production were investigated at different temperatures (30-37°C) and CO gas contents (30-70%) in batch gas fermentation. Hexanol production increased from 0.02 to 0.09 g/L when the cultivation temperature was lowered from 37 to 30°C. As the CO content increased from 30 to 70%, the CO consumption rate and hexanol production (yield, titer, and ratio of C6 compound to total products) increased with the CO content. When 70% CO gas was repeatedly provided by flushing the headspace of the bottles at 30°C, the total alcohol production increased to 4.32 g/L at the expense of acids. Notably, hexanol production (1.90 g/L) was higher than that of ethanol (1.20 g/L) and butanol (1.20 g/L); this is the highest level of hexanol produced in gas fermentation to date and the first report of hexanol as the main product. Hexanol production was further enhanced to 2.34 g/L when 2 g/L ethanol was supplemented at the beginning of 70% CO gas refeeding fermentation. Particularly, hexanol productivity was significantly enhanced to 0.18 g/L/day while the supplemented ethanol was consumed, indicating that the conversion of ethanol to acetyl-CoA and reducing equivalents positively affected hexanol production. These optimized culture conditions (gas fermentation at 30°C and refeeding with 70% CO gas) and ethanol supplementation provide an effective and sustainable approach for bio-hexanol production.

Assessment of pathogens and risk factors associated with bloodstream infection in the year after pediatric liver transplantation.

BACKGROUND: Bloodstream infection (BSI) is one of the most significantly adverse events that can occur after liver transplantation (LT) in children. AIM: To analyze the profile of BSI according to the postoperative periods and assess the risk factors after pediatric LT. METHODS: Clinical data, collected from medical charts of children (n = 378) who underwent primary LT, were retrospectively reviewed. The primary outcome considered was BSI in the first year after LT. Univariate and multivariate analyses were performed to identify risk factors for BSI and respective odds ratios (ORs). RESULTS: Of the examined patients, 106 (28%) experienced 162 episodes of pathogen-confirmed BSI during the first year after LT. There were 1.53 ± 0.95 episodes per children (mean ± SD) among BSI-complicated patients with a median onset of 0.4 mo post-LT. The most common pathogenic organisms identified were Coagulase-negative staphylococci, followed by Enterococcus spp. and Streptococcus spp. About half (53%) of the BSIs were of unknown origin. Multivariate analysis demonstrated that young age (≤ 1.3 year; OR = 2.1, P = 0.011), growth failure (OR = 2.1, P = 0.045), liver support system (OR = 4.2, P = 0.008), and hospital stay of > 44 d (OR = 2.3, P = 0.002) were independently associated with BSI in the year after LT. CONCLUSION: BSI was frequently observed in patients after pediatric LT, affecting survival outcomes. The profile of BSI may inform clinical treatment and management in high-risk children after LT.

Generation of a Dystrophin Mutant in Dog by Nuclear Transfer Using CRISPR/Cas9-Mediated Somatic Cells: A Preliminary Study.

Dystrophinopathy is caused by mutations in the dystrophin gene, which lead to progressive muscle degeneration, necrosis, and finally, death. Recently, golden retrievers have been suggested as a useful animal model for studying human dystrophinopathy, but the model has limitations due to difficulty in maintaining the genetic background using conventional breeding. In this study, we successfully generated a dystrophin mutant dog using the CRISPR/Cas9 system and somatic cell nuclear transfer. The dystrophin mutant dog displayed phenotypes such as elevated serum creatine kinase, dystrophin deficiency, skeletal muscle defects, an abnormal electrocardiogram, and avoidance of ambulation. These results indicate that donor cells with CRISPR/Cas9 for a specific gene combined with the somatic cell nuclear transfer technique can efficiently produce a dystrophin mutant dog, which will help in the successful development of gene therapy drugs for dogs and humans.

Clinical characteristics of neonatal cholestasis in a tertiary hospital and the development of a novel prediction model for mortality.

BACKGROUND: Few studies have described the aetiologies of neonatal cholestasis, and the overall neonatal cholestasis-related mortality (NCM) rate is unclear. We investigated the aetiology and outcome of neonatal cholestasis in a tertiary hospital and developed an NCM prediction model for these patients. METHODS: Patients aged <100 days with serum direct bilirubin (DB) levels of >1.0 mg/dL were retrospectively screened. Diagnostic and laboratory data during the 8-week follow-up period after enrolment between 2005 and 2020 were extracted digitally, and medical charts were reviewed manually by clinicians. Logistic regression was used to derive a prediction model for the 1-year mortality outcome of neonatal cholestasis, and performance evaluation and external validation were conducted for the NCM prediction model. FINDINGS: We enrolled 4028 neonates with DB of >1.0 mg/dL at least once. Prematurity and birth injury (35.4%), complex heart anomalies (18.6%), liver diseases (11.4%), and gastrointestinal anomalies (9.2%) were the most common aetiologies; 398 (9.9%) patients died before one year of age. The peak value of DB was positively correlated to the 1-year mortality rate. In the multivariate analysis, simple laboratory indices, including platelet, prothrombin time, aspartate aminotransferase, albumin, direct bilirubin, creatinine, and C-reactive protein, were independent predictors of 1-year mortality outcome of complete-case subjects. Using these laboratory indices, a logistic regression-based NCM prediction model was constructed. It showed acceptable performances on discrimination (area under the curve, 0.916), calibration (slope, 1.04) and Brier scoring (0.072). The external validation of the sample (n = 920) from two other centres also revealed similar performance profiles of the NCM model. INTERPRETATION: Various aetiologies of neonatal cholestasis were identified in a tertiary hospital, resulting in unfavourable outcomes of a large proportion. The NCM prediction model may have the potential to help clinicians to be aware of high-risk neonatal cholestasis. FUNDING: Ministry of Health & Welfare, Republic of Korea.

Effect of Process Control Parameters on the Filtration Performance of PAN-CTAB Nanofiber/Nanonet Web Combined with Meltblown Nonwoven.

Nanofibers have potential applications as filters for particles with diameters <10 µm owing to their large specific surface area, macropores, and controllable geometry or diameter. The filtration efficiency can be increased by creating nanonets (<50 nm) whose diameter is smaller than that of nanofibers. This study investigates the effect of process conditions on the generation of nanonet structures from a polyacrylonitrile (PAN) solution containing cation surfactants; in addition, the filtration performance is analyzed. The applied electrospinning voltage and the electrostatic treatment of meltblown polypropylene (used as a substrate) are the most influential process parameters of nanonet formation. Electrospun polyacrylonitrile-cetylmethylammonium bromide (PAN-CTAB) showed a nanofiber/nanonet structure and improved thermal and mechanical properties compared with those of the electrospun PAN. The pore size distribution and filter efficiency of the PAN nanofiber web and PAN-CTAB nanofiber/nanonet web with meltblown were measured. The resulting PAN-CTAB nanofiber/nanonet air filter showed a high filtration efficiency of 99% and a low pressure drop of 7.7 mmH2O at an air flow rate of 80 L/min. The process control methods for the nanonet structures studied herein provide a new approach for developing functional materials for air-filtration applications.

Effects of Interval Exercise Training on Serum Biochemistry and Bone Mineral Density in Dogs.

Exercise has been suggested as a powerful intervention for health care and fitness management in humans; however, few studies have demonstrated the benefits of exercise training in dogs. The purpose of this study was to examine the effects of exercise training on heart rate (HR), bone mineral density (BMD), muscle volume (MV), and hematological and serum biomarkers in dogs. Six healthy beagles completed the interval treadmill exercise, developed on the basis of the FITT principle, two times a week for 12 weeks. To evaluate the physiological parameters, the HR values were analyzed using the Polar H10 system during the entire exercise period. At pre-and post-exercise, quantitative computed tomography and hematological and serum biochemical parameters were analyzed. The interval exercise resulted in a normal HR response and no adverse behavioral or physiological effects on the dogs. We showed that exercise improved BMD in the femur (541.6 ± 16.7 vs. 610.2 ± 27.8 HA, p < 0.01) and increased serum total alkaline phosphatase (TALP; 68.6 ± 9.2 vs. 81.3 ± 17.2, p < 0.01), aspartate aminotransferase (23.5 ± 1.0 vs. 33.5 ± 1.6, p < 0.01), and creatine kinase (114.8 ± 5.3 vs. 214.0 ± 20.8, p < 0.01) levels. There was a positive relationship between BMD and TALP (femur: r = 0.760, p = 0.004; vertebrae: r = 0.637; p = 0.025). Our findings suggest that interval exercise training is beneficial to increase BMD in the femur, and an increased TALP level would be a concomitant mechanism for enhancing BMD with exercise in dogs.

Optimal Treatment of 6-Dimethylaminopurine Enhances the In Vivo Development of Canine Embryos by Rapid Initiation of DNA Synthesis.

Artificial activation of oocytes is an important step for successful parthenogenesis and somatic cell nuclear transfer (SCNT). Here, we investigated the initiation of DNA synthesis and in vivo development of canine PA embryos and cloned embryos produced by treatment with 1.9 mM 6-dimethylaminopurine (6-DMAP) for different lengths of time. For experiments, oocytes for parthenogenesis and SCNT oocytes were cultured for 4 min in 10 µM calcium ionophore, and then divided into 2 groups: (1) culture for 2 h in 6-DMAP (DMAP-2h group); (2) culture for 4 h in DMAP (DMAP-4h group). DNA synthesis was clearly detected in all parthenogenetic (PA) embryos and cloned embryos incorporated BrdU 4 h after activation in DMAP-2h and DMAP-4h groups. In vivo development of canine parthenogenetic fetuses was observed after embryo transfer and the implantation rates of PA embryos in DMAP-2h were 34%, which was significantly higher than those in DMAP-4h (6.5%, p < 0.05). However, in SCNT, there was no significant difference in pregnancy rate (DMAP-2h: 41.6% vs. DMAP-4h: 33.3%) and implantation rates (DMAP-2h: 4.94% vs. DMAP-4h: 3.19%) between DMAP-2h and DMAP-4h. In conclusion, the use of DMAP-2h for canine oocyte activation may be ideal for the in vivo development of PA zygotes, but it was not more effective in in vivo development of canine reconstructed SCNT oocytes. The present study demonstrated that DMAP-2h treatment on activation of canine parthenogenesis and SCNT could effectively induce the onset of DNA synthesis during the first cell cycle.

High-performance bag filter with a super-hydrophobic microporous polytetrafluoroethylene layer fabricated by air-assisted electrospraying.

Reducing PM emissions from industrial sites has become increasingly important as the adverse health effects of particulate matter have been demonstrated by multiple epidemiological and toxicological studies. High-performance bag filters are often used for this purpose. We fabricated polytetrafluoroethylene (PTFE) nanoparticle (NP)-coated high-efficiency bag filters using air-assisted electrospraying (AAES) technology. AAES functionalized with a combination of airflow drag force and an applied electric field facilitates high-throughput without requiring additional purification or preparation process of a PTFE emulsion. PTFE NPs form a unique three-dimensional microporous structure on a foam-filter medium, enhancing mechanical filtration performance (diffusion and interception). Moreover, the surface hydrophobicity was significantly improved as the PTFE NPs covered the bag filter surface. These factors highlight the feasibility of large-scale implementation of PTFE NP-coated bag filters for reducing PM emissions from industrial sources.

Application of the modified handmade cloning technique to pigs.

Although somatic cell nuclear transfer (SCNT) is frequently employed to produce cloned animals in laboratories, this technique is expensive and inefficient. Therefore, the handmade cloning (HMC) technique has been suggested to simplify and advance the cloning process, however, HMC wastes many oocytes and leads to mitochondrial heteroplasmy. To solve these problems, we propose a modified handmade cloning (mHMC) technique that uses simple laboratory equipment, i.e., a Pasteur pipette and an alcohol lamp, applying it to porcine embryo cloning. To validate the application of mHMC to pig cloning, embryos produced through SCNT and mHMC are compared using multiple methods, such as enucleation efficiency, oxidative stress, embryo developmental competence, and gene expression. The results show no significant differences between techniques except in the enucleation efficiency. The 8-cell and 16-cell embryo developmental competence and Oct4 expression levels exhibit significant differences. However, the blastocyst rate is not significantly different between mHMC and SCNT. This study verifies that cloned embryos derived from the two techniques exhibit similar generation and developmental competence. Thus, we suggest that mHMC could replace SCNT for simpler and cheaper porcine cloning.

Comparison of Anti-Oxidative Effect of Human Adipose- and Amniotic Membrane-Derived Mesenchymal Stem Cell Conditioned Medium on Mouse Preimplantation Embryo Development.

Oxidative stress is a major cause of damage to the quantity and quality of embryos produced in vitro. Antioxidants are usually supplemented to protect embryos from the suboptimal in vitro culture (IVC) environment. Amniotic membrane-derived mesenchymal stem cells (AMSC) have emerged as a promising regenerative therapy, and their paracrine factors with anti-oxidative effects are present in AMSC conditioned medium (CM). We examined the anti-oxidative potential of human AMSC-CM treatment during IVC on mouse preimplantation embryo development and antioxidant gene expression in the forkhead box O (FoxO) pathway. AMSC-CM (10%) was optimal for overall preimplantation embryo developmental processes and upregulated the expression of FoxOs and their downstream antioxidants in blastocysts (BL). Subsequently, compared to adipose-derived mesenchymal stem cell (ASC)-CM, AMSC-CM enhanced antioxidant gene expression and intracellular GSH levels in the BL. Total antioxidant capacity and SOD activity were greater in AMSC-CM than in ASC-CM. Furthermore, SOD and catalase were more active in culture medium supplemented with AMSC-CM than in ASC-CM. Lastly, the anti-apoptotic effect of AMSC-CM was observed with the regulation of apoptosis-related genes and mitochondrial membrane potential in BL. In conclusion, the present study established AMSC-CM treatment at an optimal concentration as a novel antioxidant intervention for assisted reproduction.