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Developing new strawberry varieties with high level of disease resistance and superior fruit quality is critical for strawberry production. Despite the complexity of the octoploid strawberry genome, recent advances in genomics and DNA sequencing technologies have allowed us to identify causal sequence variants associated with specific phenotypes. These have enabled the development of new and improved DNA markers for integration in marker-assisted breeding (MAB) efforts. The use of MAB has significantly improved the efficiency of stacking loci responsible for disease resistance and fruit quality characteristics. The “Strawberry DNA Testing Handbook” is currently accessible in the Genome Database for Rosaceae and has been an essential resource for the national and international strawberry research community. Based on the information provided in the handbook, the UF strawberry breeding program implemented seedling selection from 2021 to 2023, retaining 25.3%, 19.2%, and 37.9% of seedlings for further evaluation in each respective year. In this report, we provide updates on DNA markers associated with disease resistance and fruit quality traits. Additionally, we demonstrate the practical implementation of these markers in high-throughput marker-assisted selection and their potential to enhance strawberry breeding.

Abstract The White Blood Cell (WBC) differential test ranks as the second most frequently performed diagnostic assay. It requires manual confirmation of the peripheral blood smear by experts to identify signs of abnormalities. Automated digital microscopy has emerged as a solution to reduce this labor-intensive process and improve efficiency. Several publicly available datasets provide various WBC subtypes of differing quality and resolution. These datasets have contributed to advancing WBC classification using machine learning techniques. However, digital microscopy of blood cells with high magnification often requires a wider depth of field, posing challenges for automatic digital microscopy that necessitates capturing multiple stacks of focal planes to obtain complete images of specific blood cells. Our dataset provides 25,773 image stacks from 72 patients. The image labels consist of 18 classes encompassing normal and abnormal cells, with two experts reviewing each label. Each image includes 10 z-stacks of cropped 200 by 200 pixel images, captured using a 50X microscope with 400 nm intervals. This study presents a comprehensive multi-focus dataset for WBC classification.

Abstract Background The plant hormone auxin plays a crucial role in regulating important functions in strawberry fruit development. Although a few studies have described the complex auxin biosynthetic and signaling pathway in wild diploid strawberry (Fragaria vesca), the molecular mechanisms underlying auxin biosynthesis and crosstalk in octoploid strawberry fruit development are not fully characterized. To address this knowledge gap, comprehensive transcriptomic analyses were conducted at different stages of fruit development and compared between the achene and receptacle to identify developmentally regulated auxin biosynthetic genes and transcription factors during the fruit ripening process. Similar to wild diploid strawberry, octoploid strawberry accumulates high levels of auxin in achene compared to receptacle. Results Genes involved in auxin biosynthesis and conjugation, such as Tryptophan Aminotransferase of Arabidopsis (TAAs), YUCCA (YUCs), and Gretchen Hagen 3 (GH3s), were found to be primarily expressed in the achene, with low expression in the receptacle. Interestingly, several genes involved in auxin transport and signaling like Pin-Formed (PINs), Auxin/Indole-3-Acetic Acid Proteins (Aux/IAAs), Transport Inhibitor Response 1 / Auxin-Signaling F-Box (TIR/AFBs) and Auxin Response Factor (ARFs) were more abundantly expressed in the receptacle. Moreover, by examining DEGs and their transcriptional profiles across all six developmental stages, we identified key auxin-related genes co-clustered with transcription factors from the NAM-ATAF1,2-CUC2/ WRKYGQK motif (NAC/WYKY), Heat Shock Transcription Factor and Heat Shock Proteins (HSF/HSP), APETALA2/Ethylene Responsive Factor (AP2/ERF) and MYB transcription factor groups. Conclusions These results elucidate the complex regulatory network of auxin biosynthesis and its intricate crosstalk within the achene and receptacle, enriching our understanding of fruit development in octoploid strawberries.

Abstract Esophageal fibrosis can develop due to caustic or radiation injuries. Umbilical cord–derived mesenchymal stem cells (UC-MSCs) are known to mitigate fibrosis in various organs. However, the potential effects of UC-MSCs on human esophageal fibrosis remain underexplored. This study investigated the anti-fibrogenic properties and mechanisms of UC-MSC-derived conditioned media (UC-MSC-CM) on human esophageal fibroblasts (HEFs). HEFs were treated with TGF-β1 and then cultured with UC-MSC-CM, and the expression levels of extracellular matrix (ECM) components, RhoA, myocardin related transcription factor A (MRTF-A), serum response factor (SRF), Yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) were measured. UC-MSC-CM suppressed TGF-β1-induced fibrogenic activation in HEFs, as evidenced by the downregulation of ECM. UC-MSC-CM diminished the expression of RhoA, MRTF-A, and SRF triggered by TGF-β1. In TGF-β1-stimulated HEFs, UC-MSC-CM decreased the nuclear localization of MRTF-A and YAP. Additionally, UC-MSC-CM diminished the TGF-β1-induced nuclear expressions of YAP and TAZ, while concurrently enhancing the cytoplasmic presence of phosphorylated YAP. Furthermore, UC-MSC-CM reduced TGF-β1-induced phosphorylation of Smad2. These findings suggest that UC-MSC-CM may inhibit TGF-β1-induced fibrogenic activation in HEFs by targeting the Rho-mediated MRTF/SRF and YAP/TAZ pathways, as well as the Smad2 pathway. This indicates its potential as a stem cell therapy for esophageal fibrosis.

Abstract Background To examine the association between glycemic status and all-cause mortality risk among individuals with dementia. Methods We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality. Results The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32–1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40–1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30–1.40), shorter-term DM (

Several Neopestalotiopsis spp. have been reported to affect strawberry worldwide. Here, we sequenced two isolates of Neopestalotiopsis 19-02 (highly virulent) and 13-481 (moderately virulent) recovered from commercial strawberry fields in Florida and generated chromosome-scale assemblies using the Oxford Nanopore Technologies and Illumina platforms. Each genome assembly for 19-02 and 13-481 contained putative telomere sequences at the 5′ and 3′ ends. By analyzing the collinearity of the two newly assembled genomes and verifying the conserved telomere sequence at the end of each chromosome, we confirmed that the genome of Neopestalotiopsis spp. consists of seven basic chromosomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis showed 98.5% of conserved core genes for both genome assemblies, 19-02 and 13-481. Phylogenetic analysis with internal transcribed spacer, beta-tubulin, and translation elongation factor regions obtained from the assemblies 19-02 and 13-481 demonstrated that the highly virulent isolate 19-02 is phylogenetically distinct from moderate virulent N. rosae 13-481. Comparative genome analysis of the high-quality reference genome assemblies provided in this study will facilitate the identification of genomic regions responsible for the different virulence of the Neopestalotiopsis pathogen to strawberry. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

Abstract Background External apical root resorption (EARR) is a common undesirable outcome of orthodontic treatment, this study aimed to identify genetic polymorphisms associated with the susceptibility to extreme orthodontic-induced EARR in a Korean population using extreme phenotype analysis sampling. Methods Genomic DNA was isolated from the saliva of 77 patients who underwent orthodontic treatment involving two maxillary premolar extractions. The patients were divided into two groups based on EARR values measured on periapical radiographs: The significant resorption group (SG, EARR ≥ 4 mm) and the normal group (NG, EARR

Abstract Background A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate the anti-fibrogenic properties and mechanisms of the conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) in a murine intestinal fibrosis model and human primary intestinal myofibroblasts (HIMFs). Methods UC/PL-MSC-CM was concentrated 15-fold using a 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned to one of four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), and (4) DSS + CM (early-phase treatment). Chronic DSS colitis and intestinal fibrosis was induced by three cycles of DSS administration. One DSS cycle consisted of 7 days of oral DSS administration (1.75%, 2%, and 2.5% DSS), followed by 14 days of drinking water. UC/PL-MSC-CM was intraperitoneally administered in the late phase (from day 50, 10 times) or early phase (from day 29, 10 times) of DSS cycles. HIMFs were treated with TGF-β1 and co-treated with UC/PL-MSC-CM (10% of culture media) in the cellular model. Results In the animal study, UC/PL-MSC-CM reduced submucosa/muscularis propria thickness and collagen deposition, which improved intestinal fibrosis in chronic DSS colitis. The UC/PL-MSC-CM significantly reduced the expressions of procollagen1A1 and α-smooth muscle actin, which DSS significantly elevated. The anti-fibrogenic effect was more apparent in the UC-MSC-CM or early-phase treatment model. The UC/PL-MSC-CM reduced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs in the cellular model. The UC/PL-MSC-CM downregulated fibrogenesis by suppressing RhoA, MRTF-A, and SRF expression. Conclusions Human UC/PL-MSC-CM inhibits TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and chronic DSS colitis-induced intestinal fibrosis. Thus, it may be regarded as a novel candidate for stem cell-based therapy of intestinal fibrosis.

Abstract Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar–alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar–alveolar hyperplasia progression, although bronchiolar–alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.

Abstract Background Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. Methods This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. Results The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72–90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. Conclusions Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

Abstract This study focused on patients with advanced open-angle glaucoma (OAG) and aimed to identify key factors for monitoring them. We included 127 such patients who were followed for seven years or more, undergoing annual ophthalmic examinations. Glaucoma progression was defined as a deterioration in either structure or function. The progression rates and risk factors were evaluated. The patients were divided into upper- and lower-half subgroups based on the reduction in intraocular pressure (IOP) from the baseline. Over an 11-year period, glaucoma progression was detected in 59 eyes (46.5%). The rate of change in mean deviation (MD) was − 0.43 dB/year for the entire population; − 0.67 dB/year for progressors; and − 0.20 dB/year for non-progressors. Hypertension and disc hemorrhage (DH) were more common in progressors compared to non-progressors (45.8 vs. 23.5%, 11.9 vs. 1.5%; P = 0.008 and P = 0.016). Multivariate Cox’s proportional hazard model revealed that the presence of DH and a better baseline MD were associated with glaucoma progression. Additionally, patients with a higher percentage reduction in IOP (> 20.94%) had a lower risk of progression compared to those with less reduction. Inadequate IOP reduction, better baseline MD, presence of DH, and lower central corneal thickness were identified as risk factors for progression in advanced OAG patients.

Abstract Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD. .

Understanding gene function is important for crop improvement and breeding efforts, especially in a genetically complex polyploid plant species such as the octoploid strawberry. Agrobacterium-mediated transient assays are a widely used tool for investigating gene functions and offer a reliable alternative to stable transformation. However, variability in tissue-specific responses and inconsistent applicability of Agrobacterium-mediated transient assay across diverse plant species can be challenging. In this study, we provide a method utilizing Agrobacterium-mediated transient expression to examine the function of genes in octoploid strawberry. Our approach encompasses leaf, root, and fruit tissues, providing a comprehensive strategy for validating gene functions in strawberries. Through meticulous optimization and validation in planta, this method offers valuable insights into gene function in strawberry functional genomics and genetics research. By addressing tissue-specific variability, our methodology serves as a valuable technical resource that could facilitate advancements in identifying gene functions in octoploid strawberry.

Abstract We investigated the effects of peripheral cooling using chemotherapy gloves and socks at three cooling temperatures on subjective perceptions. The hands and feet were cooled with 8, 11, and 14°C by water-perfused gloves or socks. Nine females participated in six experimental conditions: hands or feet cooling at 8, 11, and 14°C. The heat was extracted at 3.8, 5.4, and 7.7 kJ·min1 via the gloves and at 4.1, 6.0, and 9.0 kJ·min-1 via the socks. While the results showed that overall subjective perceptions did not differ among the three temperatures (~ 9.0 kJ·min-1), there were significant differences in local thermal comfort, pain sensation, and pain discomfort among the three cooling temperatures (P

Abstract We aimed to evaluate root parallelism and the dehiscence or fenestrations of virtual teeth setup using roots isolated from cone beam computed tomography (CBCT) images. Sixteen patients undergoing non-extraction orthodontic treatment with molar distalization were selected. Composite teeth were created by merging CBCT-isolated roots with intraoral scan-derived crowns. Three setups were performed sequentially: crown setup considering only the crowns, root setup-1 considering root alignment, and root setup-2 considering the roots and surrounding alveolar bone. We evaluated the parallelism and exposure of the roots and compared the American Board of Orthodontics Objective Grading System (ABO-OGS) scores using three-dimensionally printed models among the setups. The mean angulation differences between adjacent teeth in root setups-1 and -2 were significantly smaller than in the crown setup, except for some posterior teeth (p

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

SiO is an adequate anode material for next generation lithium-ion batteries, but little is known about its aging mechanism. Here, the authors report thermal instability of the graphite/SiO composite anode induced by the accelerated loss of lithium from SiO and have elucidated the interplay between graphite and SiO.

Abstract Current method of analyzing three-dimensional soft tissue data, especially in the frontal view, is subjective and has poor reliability. To overcome this limitation, the present study aimed to introduce a new method of analyzing soft tissue data reconstructed by marching cube algorithm (Program S) and compare it with a commercially available program (Program A). Cone-beam computed tomography images of 42 patients were included. Two orthodontists digitized six landmarks (pronasale, columella, upper and lower lip, right and left cheek) twice using both programs in two-week intervals, and the reliability was compared. Furthermore, computer-calculated point (CC point) was developed to evaluate whether human error could be reduced. The results showed that the intra- and inter-examiner reliability of Program S (99.7–100% and 99.9–100%, respectively) were higher than that of Program A (64.0–99.9% and 76.1–99.9%, respectively). Moreover, the inter-examiner difference of coordinate values and distances for all six landmarks in Program S was lower than Program A. Lastly, CC point was provided as a consistent single point. Therefore, it was validated that this new methodology can increase the intra- and inter-examiner reliability of soft tissue landmark digitation and CC point can be used as a landmark to reduce human error.

Background : The prevalence of obesity has been continuously increasing, especially in rural areas of South Korea. Therefore, it is important to examine various genetic, behavioral, and environmental factors associated with obesity in these rural areas. The Korean Society for the Study of Obesity commenced a community-based prospective cohort study of the Gangwon area called the Gangwon Obesity and Metabolic Syndrome (GOMS) study to investigate longitudinal changes in the status of obesity and its related factors. Methods : A total of 317 adults 40-69 years of age were recruited from Hongcheon and Inje districts, Gangwon province, as part of the first wave of this cohort study. Information on participants’ demographic, behavioral, psychological, dietary, and environmental factors and past medical histories were collected by self-administered questionnaires and interviewer-administered questionnaires. Anthropometric measurements, blood tests, and a hand grip strength test were performed, and skin keratin and stool samples were collected. Among the 317 enrolled subjects, two participants who did not have anthropometric data were excluded from the data analyses, resulting in an inclusion of a total of 315 participants. Results : The mean age of the 315 participants in the GOMS initial baseline survey was 58.5 years old, 87 of them were men, and the mean body mass index was 24.7±3.7 kg/m2. Among all participants, 48.9% had hypertension, 21.4% had diabetes mellitus (DM), 55.6% had dyslipidemia, and 46.0% had metabolic syndrome (MS). Both the prevalence rates of DM and MS were significantly higher in men. Conclusion : The first baseline survey of the GOMS study was initiated, and a more detailed analysis of respondents’ data is expected to be continued. Further follow-up and additional recruitment will allow the investigation of risk factors and the etiology of obesity and its comorbidities in rural areas of Gangwon province.

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

Abstract To overcome the limitations of the conventional vacuum thermoforming manufacturing method, direct 3D printing of clear aligners has been developed. The present study investigated the thermo-mechanical and viscoelastic properties of a photocurable resin TC-85, which is a new material for the direct 3D printed clear aligners, comparing to a conventional thermoplastic material polyethylene terephthalate glycol. Dynamic mechanical analysis was performed to analyse the mechanical behaviours of the two materials at 37 °C and 80 °C, respectively. Furthermore, the shape memory property of the two materials was evaluated using a U-shape bending test, and the shape recovery ratio for 60 min at 37 °C was calculated. The results indicate that TC-85 can constantly apply a light force to the teeth when used for the 3D printed clear aligners, owing to its flexibility and viscoelastic properties. In addition, it is expected that the force decay induced by repeated insertion of the clear aligners will be reduced and a constant orthodontic force will be maintained. Furthermore, its geometric stability at high temperatures and the shape memory properties provide advantages for the clinical application.

Abstract The purpose of the present study was to explore the effects of wearing knee guards on skin blood flow and skin pressure during dynamic soccer motions. Twenty-one male subjects participated in the following two experimental conditions: wearing knee guards (KG) and no knee guards (Control). Subjects performed several consecutive soccer motions along with a standing position between each motion. Skin blood flow and skin pressure on the thigh, knee, and calf were monitored. The results showed that skin pressure had the greatest value in a sitting position for both the KG condition and Control, but the smallest during instep kicking and switching directions (P

Because of the global obesity epidemic, the incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) have increased worldwide, including among Koreans. Recently, the incidence rate of NAFLD in Korea was reported to be 45.1 per 1,000 person-years, and the prevalence as approximately 30% depending on the diagnostic methods used. The incidence of advanced fibrosis and hepatocellular carcinoma, as well as all-cause and liver-related mortality in NAFLD patients has increased substantially, imposing considerable public health costs in Korea. Genetic, demographic, environmental, and clinical factors are involved in the pathogenesis of NAFLD. Some genetic variants, such as patatin-like phospholipase domain-containing 3 (PNPLA-3) and sorting and assembly machinery component 50 (SAMM-50), play a major role in the occurrence of NAFLD. The risk of NAFLD and fibrosis increases with advancing age and in men. Nutritional factors, inadequate exercise, and sleep duration are also associated with increased risk of NAFLD. Obesity is a major risk factor for NAFLD; however, NAFLD in lean individuals has been noted in recent studies. Insulin resistance, type 2 diabetes, and metabolic syndrome and its components are closely associated with NAFLD development and liver fibrosis with various underlying mechanisms. Sarcopenia likely shares a common pathophysiology with NAFLD. The rapidly increasing incidence and prevalence of NAFLD and its complications, as well as the associated healthcare burden, warrant early assessment of NAFLD and its risk factors to prevent NAFLD-related complications in high risk groups.

Abstract Background Lung injury elicited by respiratory exposure to humidifier disinfectants (HDs) is known as HD-associated lung injury (HDLI). Current elucidation of the molecular mechanisms related to HDLI is mostly restricted to fibrotic and inflammatory lung diseases. In our previous report, we found that lung tumors were caused by intratracheal instillation of polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. However, the lung cancer-related genetic changes concomitant with the development of these lung tumors have not yet been fully defined. We aimed to discover the effect of long-term exposure of PHMG-p on normal human lung alveolar cells. Methods We investigated whether PHMG-p could increase distorted homeostasis of oncogenes and tumor-suppressor genes, with long-term and low-dose treatment, in human pulmonary alveolar epithelial cells (HPAEpiCs). Total RNA sequencing was performed with cells continuously treated with PHMG-p and harvested after 35 days. Results After PHMG-p treatment, genes with transcriptional expression changes of more than 2.0-fold or less than 0.5-fold were identified. Within 10 days of exposure, 2 protein-coding and 5 non-coding genes were selected, whereas in the group treated for 27–35 days, 24 protein-coding and 5 non-coding genes were identified. Furthermore, in the long-term treatment group, 11 of the 15 upregulated genes and 9 of the 14 downregulated genes were reported as oncogenes and tumor suppressor genes in lung cancer, respectively. We also found that 10 genes of the selected 24 protein-coding genes were clinically significant in lung adenocarcinoma patients. Conclusions Our findings demonstrate that long-term exposure of human pulmonary normal alveolar cells to low-dose PHMG-p caused genetic changes, mainly in lung cancer-associated genes, in a time-dependent manner.

Abstract We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing.

BackgroundThis study using multi-center health examination data from Korean adults was conducted to confirm changes in weight, and their related cardiometabolic parameters, before and after strengthening of social distancing regulations.MethodsA retrospective cohort study was conducted using health check-up data from 13 university hospitals. The study period was from January 2018 to July 2020. To examine the effect of systematic social distancing measures, participants who underwent a health check-up (Visit 3) between July 2020 and July 2021 (during full scale social distancing), and had undergone two previous health check-ups (Visits 1 and 2) between January 2018 and June 2020 (before social distancing), were selected. In total, data from 7,875 participants were analyzed. Linear mixed-effect models were used to calculate estimates of anthropometric indices and metabolic markers measured on Visits 2 and 3, compared with measurements from Visit 1.ResultsThere were no significant differences in body weight, body mass index, waist circumference, and body composition on Visit 3 than on Visits 1 and 2. However, the odds of metabolic syndrome and its components, including hypertension, high glucose, diabetes, hypercholesterolemia, hypertriglyceridemia, hyper-non-high-density lipoprotein cholesterolemia, and dyslipidemia were significantly higher on Visit 3 than on Visits 1 and 2. The increase in metabolic complications was marked, particularly in relatively young adults who visited health check-up centers located in the capital area.ConclusionMetabolic syndrome and its components were significantly worse after high level social distancing, although there were no significant increases in anthropometric indices and body fat levels. Healthcare providers need to prevent and manage worsening of metabolic parameters in subpopulations prone to be more sedentary and eat unhealthy food during the COVID-19 pandemic and associated social distancing measures.

Abstract To elucidate genetic factors affecting orthodontic treatment duration, we employed targeted next-generation sequencing on DNA from the saliva of 117 patients undergoing orthodontic treatment after premolar extraction. The clinical characteristics of patients are summarized, and the association of clinical variables with treatment duration was assessed. Patients whose treatment duration deviated from the average were classified into an extreme long group or an extreme short group. We identified nine single nucleotide polymorphisms (SNPs) of six genes that significantly differed in the two groups via targeted sequencing. The frequency of the CC genotypes of WNT3A, SPP1 (rs4754, rs9138), and TNFSF11, TT genotype of SPP1 (rs1126616), and GG genotype of SFRP2 was significantly higher in the extreme long group than in the short group. In the extreme short group, the TC genotype of SPP1, AA genotype of P2RX7, CT genotype of TNFSF11, and AG genotype of TNFRSF11A tended to exhibit higher frequency than in the long group. Taken together, we identified genetic polymorphisms related to treatment duration in Korean orthodontic patients undergoing premolar extraction. Our findings could lead to further studies predicting the prolongation of the orthodontic treatment duration, and will be of great aid to patients as well as orthodontists.

Alternaria leaf blight is one of the most common diseases in watermelon worldwide. In Korea, however, the Alternaria species causing the watermelon leaf blight have not been investigated thoroughly. A total of 16 Alternaria isolates was recovered from diseased watermelon leaves with leaf blight symptoms, which were collected from 14 fields in Korea. Analysis of internal transcribed spacer (ITS) region, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and RNA polymerase II second largest subunit (RPB2) were not competent to differentiate the Alternaria isolates. On the contrary, analysis of amplicon size of the histone H3 (HIS3) gene successfully differentiated the isolates into three Alternaria subgroups, and further sequence analysis of them identified three Alternaria spp. Alternaria tenuissima, A. gaisen, and A. alternata. Representative Alternaria isolates from three species induced dark brown leaf spot lesions on detached watermelon leaves, indicating that A. tenuissima, A. gaisen, and A. alternata are all causal agents of Alternaria leaf blight. Our results indicate that the Alternaria species associated watermelon leaf blight in Korea is more complex than reported previously. This is the first report regarding the population structure of Alternaria species causing watermelon leaf blight in Korea.

Background: Exposure to air pollution can interfere with the vitamin D endocrine system. This study investigated the effects of airborne particulate matter (PM) on renal tubular cell injury in vitro and explored the underlying mechanisms. Methods: HK-2 human renal proximal tubule cells were treated with PM with or without 1,25(OH)2D3 analog, 19-Nor-1,25(OH)2D2 (paricalcitol, 10 nM) for 48 h. The dose- and time-dependent cytotoxicity of PM with or without paricalcitol was determined via cell counting kit-8 assay. Cellular oxidative stress was assessed using commercially available enzyme-linked immunosorbent assay kits. The protein expression of vitamin D receptor (VDR), cytochrome P450(CYP)27B1, CYP24A1, renin, angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was determined. Results: PM exposure decreased HK-2 cell viability in a dose- and time-dependent manner. The activities of superoxide dismutase and malondialdehyde in HK-2 cells increased significantly in the group exposed to PM. PM exposure decreased VDR and Nrf2, while increasing CYP27B1, renin, ACE, AT1, NF-kB, TNF-α, and IL-6. The expression of VDR, CYP27B1, renin, ACE, AT1, and TNF-α was reversed by paricalcitol treatment. Paricalcitol also restored the cell viability of PM-exposed HK-2 cells. Conclusion: Our findings indicate that exposure to PM induces renal proximal tubular cell injury, concomitant with alteration of vitamin D endocrine system and renin angiotensin system. Vitamin D could attenuate renal tubular cell damage following PM exposure by suppressing the renin-angiotensin system and by partially inhibiting the inflammatory response.

Three-dimensional (3D) tumor culture techniques are gaining popularity as in vitro models of tumoral tissue analogues. Despite the widespread interest, need, and present-day effort, most of the 3D tumor culturing methodologies have not gone beyond the inventors’ laboratories. This, in turn, limits their applicability and standardization. In this study, we introduce a straightforward and user-friendly approach based on standard 96-well plates with basic amenities for growing 3D tumors in a scaffold-free/scaffold-based format. Hanging drop preparation can be easily employed by flipping a universal 96-well plate. The droplets of the medium generated by the well-plate flip (WPF) method can be easily modified to address various mechanisms and processes in cell biology, including cancer. To demonstrate the applicability and practicality of the conceived approach, we utilized human colorectal carcinoma cells (HCT116) to first show the generation of large scaffold-free 3D tumor spheroids over 1.5 mm in diameter in single-well plates. As a proof-of-concept, we also demonstrate matrix-assisted tumor culture techniques in advancing the broader use of 3D culture systems. The conceptualized WPF approach can be adapted for a range of applications in both basic and applied biological/engineering research.

Abstract Background The 2018 classification of periodontal disease characterizes the disease with a multidimensional staging and grading system. The purpose of this multicenter study was to examine variations in periodontitis classification among dental practitioners with different postgraduate educational backgrounds at the University of Maryland School of Dentistry and the Loma Linda University School of Dentistry using the 2018 classification. Methods This cross-sectional observational study included two cohorts: dental practitioners with periodontal backgrounds (n1 = 31) and those with other educational backgrounds (n2 = 33). The survey instrument contained three periodontitis cases presented with the guideline of the 2018 classification and a questionnaire including closed and open-ended questions. The participants were asked to review each case and to fill out the questionnaire independently. Fisher’s exact test was conducted to examine the differences in responses between the two cohorts. Polychoric correlations were calculated to examine the relation between the level of familiarity with the 2018 classification and the accuracy of the classification. Results The distribution of item responses was significantly different between the two cohorts regarding only one item, grading for Case 1 (p = 0.01). No significant differences in accuracy between the two cohorts were observed except for two items, grading in Case 1 (p = 0.03) and staging in Case 3 (p = 0.04). There were no significant differences in risk factor identification for each case among the two cohorts (p = 1.00, Case 1; p = 0.22, Case 2). Staging in Case 3 ( $$\widehat{\rho }$$ ρ ^ = 0.52) and risk factor identification in Case 2 ( $$\widehat{\rho }$$ ρ ^ = 0.32) were significantly correlated with familiarity with the 2018 classification. Conclusion A fair level of agreement in periodontitis classification was observed among dental practitioners with different educational backgrounds when the 2018 classification was used. The periodontal cohort showed better agreement levels and partially better accuracy. Risk factor identification for periodontal disease was difficult regardless of the educational background.

Oral microbes: The populations of tonsils and saliva Analysing the microbes on tonsils and in saliva from the mouths of children in South Korea provides comparisons of the microbial populations in these distinct but nearby regions, offering possible guidance for developing new therapies for various oral diseases. Researchers in South Korea led by Yoon Shin Park at Chungbuk National University, Cheongju, and Jae Won Chang at Chungnam National University, Daejeon, examined surgically removed tonsils from 29 patients, together with samples of the patients’ saliva. They identified many specific microbe types, finding broad similarities between the populations of an individual’s tonsils and saliva. They also identified positive and negative correlations between the presence of specific microbes in the two populations. The results could guide future treatment choices, including the use of microbes to treat disease.

Abstract Background Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells. Methods Tonsil-derived mesenchymal stem cells (TMSCs) with 20–25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses. Results The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p

Accelerated tooth movement can be achieved using micro-osteoperforations (MOPs) to stimulate regeneration of the alveolar bone during minimally invasive surgical trauma. However, there is currently no standardized protocol and limited reports regarding the side effects of MOPs based on biological evidence. This study sought to evaluate the biological effects of the number of MOPs on orthodontic tooth movement (OTM) and the potential risk for root resorption. Male CD1 mice were divided into 4 groups based on the number of MOPs, as follows: Sham; 0MOP+OTM; 2MOP+OTM; and 4MOP+OTM groups. Tooth movement distance and the number of osteoclasts were higher whereas bone volume and trabecular number were lower in the 4MOP+OTM group compared to those of the 0MOP+OTM group. Immunofluorescent assay analysis indicated that the 4MOP+OTM group was positively associated with rapid cementum regeneration and periodontal ligament tissue formation. Our findings revealed that the MOP procedure affected tooth movement and did not significantly contribute to root resorption, whereas it may promote constitutive activation of cementogenesis.

BackgroundThe coronavirus pandemic has increased reliance on the internet as a tool for disseminating information; however, information is useful only when it can be understood. Prior research has shown that web-based health information is not always easy to understand. It is not yet known whether the Korean-language COVID-19 information from the internet is easy for the general public to understand. ObjectiveWe aimed to evaluate the readability of Korean-language COVID-19 information intended for the general public from the national COVID-19 portal of South Korea. MethodsA total of 122 publicly available COVID-19 information documents written in Korean were obtained from the South Korean national COVID-19 portal. We determined the level of readability (at or below ninth grade, 10th to 12th grade, college, or professional) of each document using a readability tool for Korean-language text. We measured the reading time, character count, word count, sentence count, and paragraph count for each document. We also evaluated the characteristics of difficult-to-read documents to modify the readability from difficult to easy. ResultsThe median readability level was at a professional level; 90.2% (110/122) of the information was difficult to read. In all 4 topics, few documents were easy to read (overview: 5/12, 41.7%; prevention: 6/97, 6.2%; test: 0/5, 0%; treatment: 1/8, 12.5%; P=.006), with a median 11th-grade readability level for overview, a median professional readability level for prevention, and median college readability levels for test and treatment. Difficult-to-read information had the following characteristics in common: literacy style, medical jargon, and unnecessary detail. ConclusionsIn all 4 topics, most of the Korean-language COVID-19 web-based information intended for the general public provided by the national COVID-19 portal of South Korea was difficult to read; the median readability levels exceeded the recommended ninth-grade level. Readability should be a key consideration in developing public health documents, which play an important role in disease prevention and health promotion.

Although experiments on intratracheal intubation for animals are essential for research, it remains challenging. This study aimed to validate an animal model using a flexible imaging guide system that can be conveniently and safely used as a new method to provide easy access to organs in small animals. PBS (Phosphate Buffered Saline) and PHMG (Polyhexamethylene guanidine) were administered by intratracheal intubation to 20 rodents (10 mice and 10 rats), and the changes in the lungs were observed. Results were verified using lung tissue histopathologic staining through the intratracheally administered material, which confirmed that 100% of changes in lung tissue occurred in the PHMG-injected group, where intubation was facilitated using the flexible imaging guide. The drug was conveniently and safely administered. The flexible-imaging-fiber-guide-based intratracheal drug injectable system may be conveniently used by researchers. It allows drugs to be administered quantitatively, suggesting its potential wide use in drug development and toxicity evaluation.

Objectives: Mechanical stimuli are essential for the maintenance of periodontal ligament (PDL) homeostasis. Although there are several studies on atrophic changes in PDL due to occlusal hypofunction, the underlying mechanism is still unknown. Here, we aimed to explore the changes of gene expression in occlusal hypofunctional PDL and elucidate the related role in maintaining the PDL homeostasis.Methods: To investigate the transcriptomic difference between control and hypofunctional PDL tissue from patients, RNA sequencing was performed on 34 human teeth. The atrophic changes in PDL were evaluated by histological analysis. The effect of the Bardet-Biedl syndrome 7 (BBS7) knockdown was evaluated by the RT-qPCR, Western blot, wound healing, and tubule formation assay.Results: We detected that the expression of BBS7 was downregulated in occlusal hypofunctional PDL through RNA sequencing. Dynamic changes, including the number of periodontal ligament cells, alignment of collagen fibers, diameter of blood vessels, appearance of primary cilia, and torturous oxytalan fibers, were observed following occlusal hypofunction. Furthermore, Sonic hedgehog signaling (Shh) activity was closely associated with BBS7 expression in PDL cells. In addition, the cell migration and angiogenesis were also suppressed by BBS7 knockdown in vitro.Conclusion: We suggest that BBS7 plays an essential role in maintaining Shh signaling activity for PDL homeostasis.

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV.

Background and Aims: Liposomal bupivacaine (LB) is a formulation of local anesthetic that may exert analgesia over a prolonged period. Anecdotal use of LB suggests benefit and prolonged analgesia when used to supplement infiltration blocks. Our aim was to test the effect of a bolus of LB delivered through a nerve catheter in two types of interfascial plane blocks (transversus abdominis plane and anterior subcostal quadratus lumborum). The effect was evaluated through patient self-reporting of postsurgical pain up to 48 postoperative hours. Material and Methods: Medical records of adult postoperative patients who received LB in a peripheral nerve catheter were followed retrospectively and analysed for pain scores and spread of dermatomal numbness over 48 h following the postoperative dose. A chart review of patients who qualified between June 2015 and March 2017 was performed, and clinical data were obtained from the institutional Perioperative Health Documentation System. Results: Pain scores decreased following LB bolus, and all patients reported efficient block analgesia after bolus injection. Dermatomal numbness decreased gradually and was minimal by 48 h following bolus. Conclusion: LB can be injected through a peripheral nerve catheter to prolong analgesia after catheter removal.

Background: To overcome disadvantages of germinated brown rice, we germinated rough rice and tested effects of its useful ingredients on prevention of diabetes. Objective: This study investigated the in vitro antioxidant and in vivo antidiabetic effects of rough rice (Oryza sativa L.) with hulls, before and after germination. Rough rice was germinated for 4 days and extracted with water at 120°C. Design: This study measured antioxidants and antioxidative effects and inhibitory activities against α-amylase and α-glucosidase of rough rice before and after germination and investigated antidiabetic effects of rough rice through animal experiments. Results: All these factors increased after germination. Also, α-amylase and α-glucosidase inhibition and glucose uptake by 3T3-L1 adipocytes were significantly increased after germination. Oral administration of the germinated rough rice extract for 8 weeks significantly increased insulin levels and decreased blood glucose levels in a C57BLKS/J-db/db mice model. Immunohistochemical analysis showed that germinated rough rice effectively protected against liver, kidney, and pancreatic tissue damage. Discussion: Useful ingredients in germinated rough rice could be used to prevent diabetes. Conclusions: These results suggest that germinated rough rice extract had a beneficial effect on diabetes by increasing the antioxidant activity and further purification studies are necessary to elucidate the mechanism of the extract’s antidiabetic activity.

Abstract Background The lack of anti-fibrotic agents targeting intestinal fibrosis is a large unmet need in inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Previous studies have found that perinatal tissue (umbilical cord, UC; placenta, PL)-derived mesenchymal stem cells (MSCs) reduce fibrosis in several organs. However, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of MSCs derived from UC and PL (UC/PL-MSCs) on human primary intestinal myofibroblasts (HIMFs). Methods The HIMFs were treated with TGF-β1 and co-cultured with UC/PL-MSCs. We used a small molecular inhibitor CCG-100602 to examine whether serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) are involved in TGF-β1-induced fibrogenic activation in HIMFs. The anti-fibrogenic mechanism of UC/PL-MSCs on HIMFs was analyzed by detecting the expression of RhoA, MRTF-A, and SRF in HIMFs. Results UC/PL-MSCs reduced TGF-β1-induced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs. This anti-fibrogenic effect was more apparent in the UC-MSCs. TGF-β1 stimulation increased the expressions of RhoA, MRTF-A, and SRF in the HIMFs. TGF-β1 induced the synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin through a MRTF-A/SRF-dependent mechanism. Co-culture with the UC/PL-MSCs downregulated fibrogenesis by inhibition of RhoA, MRTF-A, and SRF expression. Conclusions UC/PL-MSCs suppress TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and could be considered as a novel candidate for stem cell-based therapy of intestinal fibrosis.

To investigate the incidence status of lily viruses on Jeju island, lily samples were collected from 2015 to 2018 and examined for virus infection using reverse transcription polymerase chain reaction. Of the viral infections, mixed and single infections were 70.0% and 17.9%, respectively. The incidence of mixed infections was highest for Plantago asiatica mosaic virus (PIAMV) and Lily symptomless virus (LSV) as 43.4% in 2015; PlAMV, LSV 33.1% in 2016; LSV, Lily mottle virus (LMoV) 10.2% in 2017; and PlAMV, LSV, LMoV and Cucumber mosaic virus (CMV) 15.8% in 2018. The incidence of PlAMV was observed to be 82.0% in 2015, 49.4% in 2016, 13.6% in 2017, and 39.5% in 2018 after the first occurrence of PlAMV in 2013. No symptoms were observed for single infection with LSV. However, in the case of mixed infection with LSV and LMoV, mosaic and leaf malformation symptoms appeared. With mixed infection with LSV and CMV, pale brown necrotic spots appeared, and mosaic and leaf curling were induced. PlAMV was more common in mixed infection than in single infection, and caused necrosis following the development of reddish-brown spots. PlAMV significantly decreased the marketability of lilies owing to the generation of leaf anomalies and curls, and its symptoms were more severe in mixed infections.

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to ‘hematological system development and function’ and ‘hematological disease.’ Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract.

A facial scanner and three-dimensional computed tomography (CT) were used to evaluate the three-dimensional change in lip asymmetry before and after two-jaw surgery for 22 patients with facial asymmetry (menton deviation > 3 mm). We used the labrale superius (Ls), deviated/non-deviated-side cheilions (Ch-D/Ch-ND), and labrale inferius (Li) to construct the upper and lower lip planes to evaluate the lip asymmetry. A correlation analysis was performed to determine the factors related to the vertical change in the cheilions (ΔChZ-D/ND). In the transverse axis, Ch-D and Li moved to improve the asymmetry after surgery. All landmarks, except the Ls, moved backward in the anteroposterior axis. In the vertical axis, significant upward movement was observed in all hard tissue landmarks; however, there were no significant changes in the soft tissue. In the lip plane, the difference in the height of Ch-D and Ch-ND was significantly reduced (1.38 mm vs. 0.72 mm). In the anteroposterior axis, the ΔChZ-D/ND showed significant correlations with the mandibular setback. In the vertical axis, the ΔCh-ND showed significant correlations with the maxillary impaction of the non-deviated side. The improvement in lip asymmetry post-surgery was mainly achieved by the movement of the lower lip and Ch-D rather than the upper lip and Ch-ND.

Objective: To examine the safety and efficacy of ambulation utilizing a semi-passive and lightweight powered exoskeleton by spinal cord injury (SCI) patients.Methods: This is a multi-center, open-label, prospective cohort study across three facilities. A cohort of 40 individuals with SCI from T4-L5 was recruited into a 20-session training and assessment protocol, utilizing the SuitX Phoenix. All patients were tested using a 10-m-walk test (10 MWT), 6-min-walk test (6 MWT), and Timed up & Go test (TUG). Patient satisfaction, pain, exertion, changes in affect, as well as overall comfort and confidence were reported using a satisfaction survey, Rated Perceived Exertion (RPE) scale, and Positive and Negative Affect Schedule (PANAS). Safety outcomes, adverse events, and device malfunctions were reported.Results: Forty participants completed the study. There were no serious adverse events. All participants reported moderate to high levels of comfort and confidence using the device. All patients were able to achieve FIM of >4 on transitional movements and walking. The neurological level of injury had a statistically significant association with walking speed, WISCI-II, and FIM. Participants with an incomplete spinal cord injury had a higher FIM, faster speed, and higher WISCI-II in all outcome measures.Conclusion: This is the first study to examine the safety and efficacy of SuitX Phoenix for ambulation by SCI patients. We have shown that Phoenix is efficacious in allowing adults with SCI T4 to L5 perform walking and transitional movements. This study also reports the safety-profile of the device, user satisfaction, and psychological trends during training.