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Abstract In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2–96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes.

Abstract Texture analysis generates image parameters from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Although some parameters correlate with tumor biology and clinical attributes, their types and implications can be complex. To overcome this limitation, pseudotime analysis was applied to texture parameters to estimate changes in individual sample characteristics, and the prognostic significance of the estimated pseudotime of primary tumors was evaluated. Our subjects were 224 rectal cancer patients who underwent pretherapeutic FDG PET/CT and neoadjuvant concurrent chemoradiation therapy (CCRT). Texture parameters of the primary tumor were extracted from FDG PET/CT images acquired before neoadjuvant CCRT. The pseudotime of the primary tumor was successfully derived from texture parameters using the Phenopath tool. Clinico-pathologic features were obtained and survival analysis was performed. Pseudotime, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) demonstrated significant associations with overall survival. Unlike MTV and TLG, pseudotime was an independent prognostic factor for overall survival (hazard ratio = 4.807, p-value = 0.037). Pseudotime analysis integrates various metabolic texture parameters into a single metric. Pseudotime estimated from FDG PET/CT images of primary tumors shows superior prognostic significance to conventional PET parameters in patients with locally advanced rectal cancer treated with tri-modality therapy.

Abstract Non-small cell lung cancer (NSCLC) is histologically classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC). However, some tumors are histologically ambiguous and other pathophysiological features or microenvironmental factors may be more prominent. Here we report integrative multiomics analyses using data for 229 patients from a Korean NSCLC cohort and 462 patients from previous multiomics studies. Histological examination reveals five molecular subtypes, one of which is a NSCLC subtype with PI3K-Akt pathway upregulation, showing a high proportion of metastasis and poor survival outcomes regardless of any specific NSCLC histology. Proliferative subtypes are present in LUAD and LSCC, which show strong associations with whole genome doubling (WGD) events. Comprehensive characterization of the immune microenvironment reveals various immune cell compositions and neoantigen loads across molecular subtypes, which predicting different prognoses. Immunological subtypes exhibit a hot tumor-enriched state and a higher efficacy of adjuvant therapy.

Abstract Kidney fibrosis causes irreversible structural damage in chronic kidney disease and is characterized by aberrant extracellular matrix (ECM) accumulation. Although glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is a crucial enzyme involved in proline-rich protein synthesis, its role in kidney fibrosis remains unclear. The present study revealed that EPRS1 expression levels were increased in the fibrotic kidneys of patients and mice, especially in fibroblasts and proximal tubular epithelial cells, on the basis of single-cell analysis and immunostaining of fibrotic kidneys. Moreover, C57BL/6 EPRS1tm1b heterozygous knockout (Eprs1 +/−) and pharmacological EPRS1 inhibition with the first-in-class EPRS1 inhibitor DWN12088 protected against kidney fibrosis and dysfunction by preventing fibroblast activation and proximal tubular injury. Interestingly, in vitro assays demonstrated that EPRS1-mediated nontranslational pathways in addition to translational pathways under transforming growth factor β-treated conditions by phosphorylating SMAD family member 3 in fibroblasts and signal transducers and activators of transcription 3 in injured proximal tubules. EPRS1 knockdown and catalytic inhibition suppressed these pathways, preventing fibroblast activation, proliferation, and subsequent collagen production. Additionally, we revealed that EPRS1 caused mitochondrial damage in proximal tubules but that this damage was attenuated by EPRS1 inhibition. Our findings suggest that the EPRS1-mediated ECM accumulation induces kidney fibrosis via fibroblast activation and mitochondrial dysfunction. Therefore, targeting EPRS1 could be a potential therapeutic target for alleviating fibrotic injury in chronic kidney disease.

Abstract Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population.

Background : To analyze the anthropometric changes in women who had participated in a combined resistance and aerobic training program for more than a year and to determine the effect of the exercise on weight loss. Methods : A total of 9,128 women aged between 20 and 60 years who registered in the Curves program, which employs a combination of resistance and aerobic training exercises, and who participated for more than 1 year were included in our analysis. The women were divided into groups according to exercise frequency:

Background: This study aimed to evaluate the effects of kombucha on the surface of composite resins and to examine the degradation-inhibiting effect of adding calcium to kombucha. Methods: Six experimental groups were established, with three types of liquid kombucha: one with 3% added calcium, carbonated water as a positive control, and mineral water as a negative control. The pH and titratable acidity values of the experimental groups were measured. The samples were filled with condensed composite resin and placed in the experimental drinks for 5, 15, 30, and 60 minutes. The Vickers microhardness of the surface was measured before and after immersion, and the changes were compared. Results: The pH values of the experimental group were I’m alive (2.87±0.02), Hollys (2.95±0.01), Ediya (2.99±0.01), I’m alive +3% Ca (4.09±0.01), carbonated water (4.66±0.01), and mineral water (7.67±0.02). I’m alive (–12.35) showed the largest reduction in surface hardness, followed by Hollys (–9.78), carbonated water (–7.97), I’m alive +3% Ca (–7.82), Ediya (–7.60), and mineral water (–1.56). In the Vickers microhardness measurements, all experimental groups, except for the mineral water group, showed significant differences (p＜0.05). The scanning electron microscope results showed that the experimental group and positive control had rough surfaces and micropores. Conclusion: The surface hardness was significantly reduced in all experimental groups except for water. In particular, in the case of kombucha with low pH, the reduction rate increased, weakening the physical properties of the material. In addition, the reduction rate of surface hardness was lower in kombucha with added calcium, and it is believed that drinking kombucha containing calcium can minimize the erosion of dental materials.

Background: This study aimed to investigate the erosive potential of powdered vitamin C on the bovine enamel tooth surface. Methods: The experiment included five groups: Lemona, Vitagran, Korea Eundan, Coca-Cola (positive controls), and artificial saliva (negative controls). The pH and titratable acidity were measured. Bovine enamel specimens were immersed in the experimental solutions for 15 minutes each day for 7 days. The surface microhardness was measured using the Vickers hardness number before immersion and on the 1st, 3rd, 5th, and 7th days. The surfaces of the bovine enamel specimens were observed by scanning electron microscopy (SEM). Results: The pH of the experimental groups was as follows: Lemona (2.04±0.04) had the lowest pH, followed by Vitagran (2.56±0.01), the positive control group Coca-Cola (2.60±0.03), Korea Eundan (3.14±0.02), and the negative control group artificial saliva (7.06±0.05). Surface microhardness decreased significantly during the immersion period (p＜0.001). The largest surface microhardness reduction value was shown in Lemona (–201.22±20.60), followed by Vitagran (–190.02±14.73), Korea Eundan (–189.27±27.14), Coca-Cola (–99.28±17.21), artificial saliva (–10.99±9.94). According to the SEM findings, the experimental and positive control groups exhibited rough surfaces with micropores, whereas the negative control group exhibited smooth surfaces before specimen immersion. Conclusion: Consuming powdered vitamin C at a low pH may degrade the enamel surface. To reduce the erosive effect, it is recommended to rinse the mouth with water and brush the teeth after an hour.

Abstract Objectives This study aimed to investigate the impact of hepatic steatosis on cardiometabolic outcomes in young adults with prediabetes. Methods A nationwide cohort study was conducted with 896,585 young adults under 40 years old without diabetes or previous history of cardiovascular disease. Hepatic steatosis was identified using a fatty liver index of ≥ 60. The outcomes of this study were incident diabetes (DM) and composite major adverse cardiovascular events (MACE), including myocardial infarction, stroke, or cardiovascular death. Results During a median follow-up of 11.8 years, 27,437 (3.1%) incident DM cases and 6,584 (0.7%) MACE cases were recorded. Young adults with prediabetes had a significantly higher risk of incident DM (hazard ratio [HR]: 2.81; 95% confidence interval [CI]: 2.74–2.88; P-value:

Abstract Background Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

With the rapid advancement of metal 3D printing technologies, porous metal implants are increasingly explored for regenerative medicine. Among various methods, powder bed fusion (PBF) stands out for its precision in implant design and fabrication. This study systematically investigates the structural, mechanical, and biological aspects of titanium scaffolds using PBF technology with varying pore sizes (400 μm, 600 μm, 800 μm, and 1000 μm). Micro-CT cross-sectional images revealed slight deviations in pore size and structure thickness from the intended designs, yet the overall structure adhered closely to specifications. Mechanical testing showed that as pore size increased, both the elastic modulus and yield strength decreased, with scaffolds in the 600–1000 μm range resembling the properties of human cortical bone. Osteoblast proliferation and differentiation were most active in scaffolds with 1000 μm pores, whereas endothelial cell proliferation thrived in 400 μm pores. To simultaneously enhance mechanical properties, osteointegration, and vascularization, scaffolds with a gradient in pore sizes from 400 μm to 1000 μm were designed and evaluated. These graded scaffolds demonstrated mechanical properties comparable to human cortical bone. In vitro experiments further supported the advantages of pore-size gradients, revealing accelerated osteoblast and endothelial proliferation in the Type 2 gradient scaffolds, featuring a gradient from the center (1000 μm) to the periphery (400 μm). Collectively, these findings suggest that the design strategy of the Type 2 gradient scaffold is beneficial not only for achieving biomechanical compatibility by closely mimicking natural bone but also for promoting osteogenesis and neovascularization.

Peyronie’s disease is an acquired condition characterized by penile deformities caused by fibrosis of the penile tunica albuginea, leading to symptoms such as penile pain, erectile dysfunction, and other associated issues. Despite extensive research, the pathophysiology of this condition remains poorly understood, and standardized diagnostic and treatment protocols are lacking. While clinical guidelines from several professional societies exist, they do not consistently account for factors such as patient ethnicity, geography, and socioeconomic status. Thus, the Korean Society for Sexual Medicine and Andrology (KSSMA) aimed to develop recommendations tailored to clinical practice in Korea. These recommendations summarize the latest evidence, including clinical practice guidelines from various international professional societies, and represent the consensus opinion of an expert group within the KSSMA. They encompass all aspects of Peyronie’s disease, including the definition, diagnosis, non-surgical interventions, and surgical treatment options.

Abstract Tumor budding is a significant prognostic factor in colorectal cancer (CRC) management and is graded as follows: 0–4 buds as low, 5–9 buds as intermediate, and > 10 buds as high. However, the specific prognostic difference between cases with 0 buds (BD0) and those with 1–4 buds (BD1) is not well established owing to a lack of comparative studies. This study aimed to examine and compare the rate of lymph node (LN) metastasis and prognosis by distinguishing between BD0 and BD1 within the low-grade category (0–4 buds) of tumor budding in submucosa (T1) and muscularis propria (T2) CRC. We retrospectively identified 223 cases of T1 and T2 CRC underwent surgery from 2015 to 2018 across three medical institutions using medical records. Pathology, including assessing tumor budding, was subsequently reconfirmed, and the recurrence and survival of patients were evaluated up to December 2023. Patients in the BD1 group exhibited a higher T stage than those in the BD0 group, accompanied by significantly increased rates of lymphovascular and perineural invasion. The prevalence of LN metastasis was 14.8%. No significant differences in LN metastasis were observed between the BD0 and BD1 groups. In a multivariate analysis exploring factors associated with LN metastasis, relevant factors included lymphatic invasion, perineural invasion, and ≥ 5 buds. There were no significant differences in 5-year survival and progression free survival rates between the BD0 and BD1 groups (P = 0.971). This study confirmed that there was no significant difference in LN metastasis or prognosis between patients with BD0 and BD1.

Abstract In patients with gastroesophageal reflux disease (GERD) whose symptoms improve with acid-suppression therapy, on-demand treatment could constitute maintenance therapy. This study investigated the comparative efficacy and safety of on-demand tegoprazan and proton-pump inhibitor (PPI) therapy in GERD. From six university hospitals in the Daejeon-Chungcheong region, we enrolled patients with GERD who had experienced symptomatic improvement with acid-suppressive therapy and, using a randomization table, randomly allocated these participants to two groups: to receive either tegoprazan 50 mg + esomeprazole placebo or tegoprazan placebo + esomeprazole 20 mg, respectively. The primary endpoint of this study was the intergroup difference in patient satisfaction with on-demand therapy. Among the 69 participants who completed 8 weeks of on-demand therapy and rated patient satisfaction on a 5-point Likert scale, the tegoprazan and esomeprazole groups scored an average of 4.31 and 4.15 points, respectively, without any significant intergroup difference. In the tegoprazan group, 26.2% (182/694) of those with episodes experienced symptom improvement within 30 min, which is a significantly higher proportion compared to 16.1% (104/646) in the esomeprazole group. Compared to the esomeprazole group, the tegoprazan group had a significantly shorter time to symptom improvement overall and a significantly higher proportion of patients who improved within 30 min. No serious treatment-emergent adverse events were reported. Tegoprazan is effective as on-demand therapy for GERD and offers the expectation of faster symptom improvement than with PPIs. Clinical trial KCT0009296, registered at cris.nih.go.kr.

Abstract We investigated the safety and performance of the Da Vinci SP single-port robot (SP robot) in nipple-sparing mastectomy (NSM) with immediate reconstruction. Medical records of 60 women aged ≥ 19 years who had undergone SP robot-assisted unilateral or bilateral NSM with immediate reconstruction between October 2020 and August 2021 were retrospectively analyzed. Stage I (31, 47.1%) was the most common pathological tumor-node-metastasis stage, followed by stages II (22, 33.3%), 0 (7, 10.6%), and III (4, 6.0%). The median total duration of NSM performed by a breast surgeon and reconstruction performed by a plastic surgeon was 154.0 min (interquartile range [IQR], 130.5–206.0 min) and 133.0 min (IQR, 80.0–255.0 min), respectively. The median length of hospitalization was 5.5 days (IQR, 3.0–9.0 days). Conversion to robotic multiport or open surgery was not required in any case. The median duration to drain removal was 5.0 days (IQR, 4.0–6.0 days). Recurrence of cancer within 6 months was not observed in any patient. SP robot-assisted NSM with immediate reconstruction was performed successfully in all patients without conversion to open surgery or the incidence of significant perioperative complications, indicating its precision and ability to minimize the size of the surgical incision.

"Purpose: This study aims to develop and implement an economic evaluation using a micro-costing approach to provide a precise and transparent analysis of the direct costs of cystoscopic procedures in Korean hospitals. The study seeks to identify key cost components and evaluate whether current reimbursement rates accurately reflect these direct costs. Materials and Methods: Significant variations in cost items were identified across different studies. An economic evaluation was conducted using a micro-costing methodology for the cost analysis of cystoscopic procedures, developed through literature review, data collection from studies, and expert consultations. Results: Gangnam Severance Hospital (GSH) performed 2,188 cystoscopic procedures, including 1,847 cystoscopies and 341 JJ stent removals, with average costs of $100.8 and $110.6, respectively. At National Health Insurance Service Ilsan Hospital (NHIMC), 1,463 procedures were performed, including 1,167 cystoscopies and 296 JJ stent removals, with average costs of $119.2 and $125.3. Cystoscopy costs at GSH were driven by reprocessing ($45.8, 45.4%) and equipment ($33.1, 32.9%), while NHIMC’s were $52.5 (44.0%) for equipment and $48.7 (40.8%) for reprocessing. Both hospitals incurred financial losses, with NHIS (National Health Insurance Service) covering only about 71.7% and 60.6% of costs for cystoscopy, and 71.0% and 62.7% for JJ stent removal. Conclusions: The significant discrepancy between HIRA (Health Insurance Review & Assessment Service)’s estimated costs and those identified here suggests that current fees for cystoscopic procedures may be underestimated and require reassessment. Given the results, reevaluating these rates is essential to ensure fair compensation for healthcare providers and to deliver optimal patient care."

Abstract To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated. The resolution of subretinal fluid(SRF), intraretinal fluid(IRF), and serous pigment epithelial detachment(PED) was also assessed. In addition, factors associated with complete resolution of SRF and IRF were investigated. A total of 69 patients were included in this study. BCVA significantly improved from a mean logarithm of minimal angle of resolution of 0.64 ± 0.41 at baseline to 0.47 ± 0.39 at 3 months (P

Abstract Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has emerged as a successful treatment modality for various malignancies. However, TILs cultured from colorectal cancer (CRC) liver metastasis remain underexplored. Fifteen CRC liver metastasis tissues underwent initial expansion (IE) of TILs and rapid expansion (REP). Histologic examination including the level of stromal TILs and Klintrup-Mäkinen score, were assessed by pathologists and deep learning-derived spatial analysis. We performed correlation analysis between expanded TILs and histopathologic factors. All cases exhibited successful IE, with a mean IE TIL count per fragment and total IE TIL per case of 2.59 ± 2.79e5 cells and 167.79 ± 126.97e5 cells, respectively. Five cases underwent REP, with a median fold change of 3,610 (range, 1,136–4,925). The median CD4+/CD8 + ratio in IE TILs and REP TILs were 3.66 and 0.68, respectively. A significant correlation was observed between the mean number of expanded TILs per fragment and KM score (p = 0.022). Successful expansion of TILs from CRC liver metastasis was achieved. Assessment of KM score may serve as a predictive tool for the obtainable TILs before IE. These findings lay the groundwork for future studies to establish effective ACT in patients with metastatic CRC.

Abstract Genome mining is a promising avenue for expanding the repertoire of microbial natural products, which are important for drug development. This approach involves predicting genetically encoded small molecules by examining bacterial genomes via accumulated knowledge of microbial biosynthesis. However, it is also important that the microbes produce the predicted molecule in practice. Here, we introduce an endophytic Streptomyces sp. N50, which was isolated from the medicinal plant Selaginella tamariscina. Upon sequencing its entire genome, 33 biosynthetic gene clusters (BGCs) were identified in a chromosome and a megaplasmid. Subsequent genome mining revealed that the new 15-deoxynaphthomycin could be produced due to the presence of an enoyl reductase domain, which is absent in the known BGC of naphthomycin, a type of ansamycin antibiotics. In addition, the engineered strain with the introduction of the global regulatory gene afsR2 into N50 successfully produced 15-deoxynaphthomycins. Furthermore, molecular network analysis via MS/MS selectively confirmed the presence of additional sulfur-containing 15-deoxynaphthomycin congeners. Eventually, six new 15-deoxynaphthomycins were isolated and elucidated from the engineered strain N50. This family of compounds is known to exhibit various biological activities. Also, the presence of quinone moieties in these compounds, which are known to activate NRF2, they were tested for their ability to activate NRF2. Among the new compounds, three (1, 5, and 6) activated the antioxidant NRF2-ARE signaling pathway. Treatment with these compounds significantly elevated NRF2 levels in HepG2 cells and further induced the expression of NRF2 target genes associated with the antioxidant response. This study suggests that the combination of genome mining, gene engineering and molecular networking is helpful for generating new small molecules as pharmaceutical candidates from microorganisms.

Objectives We investigated the impact of an advanced “Nutrition Education Program” on patients with Diabetes mellitus, type 2 from public health centers enrolled in a primary health care-based chronic disease management project. This 12-week dietary management program was developed by the Korea Health Promotion and Development Institute. We assessed if this program improved glycemic control and other health indicators through dietary and nutritional improvements. Methods Seventeen patients with Diabetes mellitus type 2 were enrolled in the “Nutrition Education Program.” These patients were referred to public health centers for lifestyle management based on physician assessments at local clinics that were participating in a pilot project on primary health care-based chronic disease management. The participants attended the program comprising face-to-face basic, in-depth, and practical training sessions at the health center during the third, fifth, and seventh weeks, respectively. Anthropometric measurements, body composition analysis, blood biochemical characteristics, nutritional knowledge, and self-efficacy evaluation were performed before and after the program. Data were analyzed using SPSS ver. 28.0. Results The mean age of the participants was 62 years, and most participants were female (14, 82.4%). No significant changes in patients’ anthropometric measurements or body composition were observed after the training. However, significant reductions were observed in the blood biochemical characteristics, including glycated hemoglobin, total cholesterol, and low-density lipoprotein levels. Additionally, patients’ nutritional knowledge and self-efficacy scores increased significantly. Conclusions The “Nutrition Education Program” helped in improving glycemic control and other health indicators in patients with Diabetes mellitus type 2. Further research is required to objectively confirm the long-term and sustained effects of the program in a controlled study. Trial Registration Clinical Research Information Service Identifier: KCT0010010.

Abstract Background Predicting the length of stay in advance will not only benefit the hospitals both clinically and financially but enable healthcare providers to better decision-making for improved quality of care. More importantly, understanding the length of stay of severe patients who require general anesthesia is key to enhancing health outcomes. Objective Here, we aim to discover how machine learning can support resource allocation management and decision-making resulting from the length of stay prediction. Methods A retrospective cohort study was conducted from January 2018 to October 2020. A total cohort of 240,000 patients’ medical records was collected. The data were collected exclusively for preoperative variables to accurately analyze the predictive factors impacting the postoperative length of stay. The main outcome of this study is an analysis of the length of stay (in days) after surgery until discharge. The prediction was performed with ridge regression, random forest, XGBoost, and multi-layer perceptron neural network models. Results The XGBoost resulted in the best performance with an average error within 3 days. Moreover, we explain each feature’s contribution over the XGBoost model and further display distinct predictors affecting the overall prediction outcome at the patient level. The risk factors that most importantly contributed to the stay after surgery were as follows: a direct bilirubin laboratory test, department change, calcium chloride medication, gender, and diagnosis with the removal of other organs. Our results suggest that healthcare providers take into account the risk factors such as the laboratory blood test, distributing patients, and the medication prescribed prior to the surgery. Conclusion We successfully predicted the length of stay after surgery and provide explainable models with supporting analyses. In summary, we demonstrate the interpretation with the XGBoost model presenting insights on preoperative features and defining higher risk predictors to the length of stay outcome. Our development in explainable models supports the current in-depth knowledge for the future length of stay prediction on electronic medical records that aids the decision-making and facilitation of the operation department.

Abstract Abeliophyllum distichum and Forsythia ovata are closely related species endemic to Korea and are highly valued as ornamental shrubs in the Oleaceae family. A combination of PacBio and Illumina sequencing with Hi-C scaffolding technologies was employed to develop chromosome-level genome assemblies of these species. The assembled genome sizes are 795.72 Mb for A. distichum and 1,108.53 Mb for F. ovata. The assemblies exhibit scaffold N50 lengths of 53.12 Mb and 68.97 Mb, with minimal gaps measuring 323.40 kb and 149.00 kb, and 97.71% and 98.82% BUSCO scores for Embryophyta single-copy orthologs, respectively, indicating high contiguity and completeness. The genomes contain 485.24 Mb and 691.68 Mb of repetitive sequences, 4,926 and 7,175 full-length long terminal repeat retrotransposons, and 49,414 and 57,587 protein-coding genes, respectively. The 14 pseudochromosomes encompass 93.80% of the A. distichum genome and 89.11% of the F. ovata genome, thereby demonstrating one-to-one chromosome-level collinearity. These high-quality genome assemblies serve as invaluable resources for genetic and breeding studies, facilitating a deeper understanding of the evolutionary history of these distinctive species.

Abstract We reported in a previous study that wood fiber orthogonal grooving improves flame retardant vacuum-pressure impregnation performance. However, it was limited to small sample sizes. We extended our previous study to investigate the effect of grooving on flame retardant impregnation in Japanese cedar (Cryptomeria japonica D. Don.) and Korean larch (Larix kaempferi (Lamb.) Carriere) full-size timber [2,400 mm(L) × 100 mm(W) × 22 mm(T)], which are widely used as a building interior lining. Japanese cedar had higher open-pore porosity and gas permeability than Korean larch. As a result, Japanese cedar had no significant difficulty impregnating the flame retardant, even without a grooving pretreatment process. The flame retardant's impregnating performance in Korean larch control was insignificant, but the impregnating ability was improved after fiber orthogonal grooving. In conclusion, Japanese cedar can meet the fire safety standards announced by the Ministry of Land, Infrastructure and Transport without groove processing before flame retardant impregnation. On the other hand, Korean larch had to be impregnated with a flame retardant after grooving processing in the orthogonal direction of the fiber to achieve fire safety performance. As a result, this grooving pretreatment is a simple and practical technique that can be used immediately on impervious commercial wood.

The genus Tulipa L., belonging to the Liliaceae family, has significant economic, horticultural, and ecological importance and is culturally revered in various regions worldwide. The total number of Tulipa species, including 90–120 taxa, varies based on different sources. Globally, Kazakhstan has one of the highest diversities of Tulipa species, most of which are threatened. In this study, we update and revise the Tulipa species in Kazakhstan based on field observations and an extensive herbarium specimens’ survey. A total of 41 taxa were identified, including 13 species endemic to Kazakhstan, among which seven species have been assessed as threatened globally. Furthermore, we gathered 1,942 occurrence records of 41 Tulipa taxa to analyze spatial arrangement of Tulipa species richness in Kazakhstan. Based on these results, we identified 22 grid cells with a high diversity of tulip species in southern Kazakhstan. We also present taxonomic key for all Tulipa species occurring in Kazakhstan, along with comments on their general distribution, habitat, phenology, distribution map, and conservation status. In addition, a color plate for each species is provided. Overall, our study provides valuable insights into the conservation status, distribution patterns, and biodiversity of Tulipa species in Kazakhstan, laying a foundation for targeted conservation efforts and further research in the region.

Abstract Background The main key to the 4th industrial era is robots, and wearable robots are incorporated into human healthcare. Samsung Electronics’ Bot Fit is a hip joint-centered assistive robot that can induce walking posture and energetic walking exercises. Methods This study is a cross-section study. Fifty-eight subjects consisting of older and younger adults participated. The straight walking test was conducted under the conditions of bare body, wearing the wearable robot Bot Fit assist mode, and applying voice coach. Spatio-temporal gait parameters were analyzed and the statistical significance level was set at 0.05. Results When assist mode and voice coach were applied, pelvic movement in 3 axes, stride length, and walking speed compared to the bare body increased. In young adults, stride length difference decreased in assist mode 1 and voice coach 1 compared to the bare body. Conclusion Bot Fit’s assist mode and voice coach method positively influence walking efficiency, posture, stride length, and speed, though potential interaction effects between these interventions should be considered. Personalized, real-time adjustments show promise for optimizing walking exercises, warranting further investigation into their long-term and population-specific effects. Trial registration Clinical Research Information Service, KCT0007974. Registered 12/07/2022.

Abstract The immune system continuously interacts with tumors, possibly leading to systemic alterations in circulating immune cells. However, the potential of these cancer-associated changes for diagnostic purposes remains poorly explored. To investigate this, we conducted a comprehensive flow cytometric analysis of 452 peripheral blood mononuclear cell (PBMC) samples from 206 non-small-cell lung cancer (NSCLC) patients, 100 small-cell lung cancer (SCLC) patients, 94 healthy individuals, and 52 benign lung disease (BLD) patients. We focused specifically on circulating T cells, given their close interaction with tumors, and initially assessed 93 T-cell features from the flow cytometric analysis. Using a feature selection protocol, we identified five T-cell features in peripheral blood with strong diagnostic relevance. Notably, while individual alterations in these features lacked cancer specificity, simultaneous alterations were uniquely indicative of lung cancer. To comprehensively analyze these features, we developed a scoring model, “IMmunoPhenotypic Analysis for Cancer deTection (IMPACT).” Comprehensive analysis using the five features (IMPACT-5) demonstrated high cancer specificity and biomarker efficacy, as evidenced by the high area under the receiver operating characteristic curve values for lung cancer patients (0.9187, 0.9277, and 0.9363 for stage I NSCLC, stage IV NSCLC, and SCLC patients, respectively), in stark contrast to BLD patients (0.5212). These findings suggest that comprehensive analysis of cancer-associated changes in circulating T cells can effectively detect lung cancer from its early stages, proposing immunophenotypic analysis of circulating T cells as an innovative liquid biopsy-based diagnostic biomarker.

Zonula occludens (ZO) proteins serve as scaffolding proteins that provide structural support at cell junctions and the cytoplasmic surface, acting as bridges between integral membrane proteins and the cytoskeleton. In addition to their structural functions, they also regulate cell growth and proliferation. Recent studies have shown that ZO proteins are involved in various diseases, including cancer. Specifically, ZO proteins influence the growth and development of cancer cells in the tumor microenvironment. These proteins perform various functions in the tumor microenvironment through processes such as angiogenesis, inflammatory responses, epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The mechanisms of these actions may vary depending on the type of cancer and environmental conditions. Ongoing research explores several signaling pathways involving ZO proteins. These insights suggest that new therapeutic approaches may be considered to slow down cancer growth and development within the tumor microenvironment. Despite continuing research on the cellular and in vivo roles of ZO proteins, the current understanding of how these signaling mechanisms function within the tumor microenvironment in vivo remains limited. In this review, we introduce the characteristics and regulatory mechanisms of ZO proteins in the cancer microenvironment, explore their potential to suppress cancer cell environments, and examine their roles in vivo.

Metal-supported solid oxide fuel cells are gaining attention for their economic advantages, robust mechanical properties, and resilience to thermal cycling. However, gas transport may be impeded by the dense and irregular microstructure of the metal support, which would reduce electrochemical efficiency. To address this challenge, polymethylmethacrylate, a pore-forming agent that can offer porosity and uniform pore distribution, has been employed in this study. Ni-Fe metal supports with a uniform microstructure have been successfully fabricated by adding the pore former. The porosity of the supports is controlled by varying the amount (0–15 wt%) of the pore former. The electrochemical performance of the Ni-Fe supported solid oxide fuel cells has been then examined. As a result, the highest power density has been achieved in the most porous cell (15 wt%), showing that the more porous the metal support, the better the electrochemical performance.

Background The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Highlights We have discovered a novel phenomenon where the pseudocapacitance of flexible MXene supercapacitors changes sensitively in response to bending, leading to the development of Pseudocapacitive Sensors. Pseudocapacitive Sensors repurpose supercapacitors as strain sensors, detecting capacitance changes from shifts between pseudocapacitance and electrical double layer capacitor. These highly sensitive sensors have a gauge factor of about 1200, far exceeding that of conventional strain sensors.

Abstract Aims An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. Methods We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate‐user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate‐naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. Results During a median follow‐up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630–0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553–0.934) and 0.655 (0.492–0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591–0.929) and 0.750 (0.609–0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. Conclusion The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

Phytophthora root and stem rot, caused by Phytophthora sojae, considerably reduces soybean yield worldwide. Our previous study identified two genomic regions on chromosome 18 (2.1–2.6 and 53.1–53.3 Mbp) that confer resistance to the P. sojae isolate 2457, through linkage analysis using progenies derived from the Daepung × Socheong2 population. These two regions contained 51 and 19 annotated genes, respectively. However, the specific gene responsible for resistance to P. sojae isolate 2457 has yet to be identified. In this study, we performed a comparative transcriptomic analysis of Socheong2 and Daepung, two Korean soybean varieties identified as resistant and susceptible to P. sojae isolate 2457, respectively. RNA sequencing was conducted on tissue samples collected at 0, 6, and 12 hours after inoculation (HAI), and significant differences in the expression of defense-related genes were observed across time points and between the two cultivars. Genes associated with the jasmonic acid, salicylic acid, ethylene, and systemic acquired resistance pathways were upregulated in both cultivars at 6 and 12 HAI compared to 0 HAI, with these biological processes were more strongly upregulated in Socheong2 compared to Daepung at 6 and 12 HAI. A comparison of differentially expressed genes (DEGs) and candidate genes within the previously identified QTL regions revealed an ortholog of the HS1 PRO-1 2 gene from Arabidopsis thaliana among the upregulated DEGs in Socheong2, particularly at 12 HAI compared to 0 HAI. This study will aid in targeted breeding efforts to develop soybean varieties with improved resistance to P. sojae.

Watermelon mosaic virus (WMV), a member of the genus Potyvirus, causes serious economic losses in cucurbit crops. For molecular biological studies of viruses, it is necessary to construct an infectious clone that can facilitate gene functional analysis. In this study, we constructed an infectious cDNA clone of WMV genomic RNA by Gibson assembly and evaluated its virulence and symptoms on a variety of host plants. A WMV isolate (WMV-IS-me2) collected from melon in Iksan, Jeonbuk Province, Korea in 2015 caused mosaic symptoms on leaves. Four overlapping PCR fragments of the full-length genome of this isolate and the pJL89 binary vector with overhanging ends of 40 bp were amplified by reverse transcription PCR and joined in a single isothermal reaction. The complete nucleotide sequence of the infectious cDNA clone of WMV was determined and the recombinant vector was transformed into Agrobacterium tumefaciens GV3101. Following agro-infiltration, an infectious clone (pWMV-M, KACC95145P) systemically induced mosaic symptoms on watermelon (Citrullus lanatus), zucchini (Cucurbita pepo), melon (Cucumis melo), and Nicotiana benthamiana plants. This infectious clone may be useful for screening cucurbit varieties resistant to WMV, as well as for studying viral gene function.

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.

Abstract Inflammatory bowel disease is associated with a high risk of colitis-associated cancer (CAC). We evaluated the role of TLR3 in CAC using a murine model. Wild-type (WT) and TLR3-knockout (TLR3−/−) mice received azoxymethane (AOM) 12.5 mg/kg intraperitoneally on day zero, followed by three cycles of 2% dextran sulfate sodium (DSS) for five days and free water for two weeks. We evaluated clinical indices, such as weight change, colon length, histological severity of colitis, and tumor number. We performed immunofluorescence assays for phospho-IκB kinase and β-catenin in colon tissues. To elucidate the antitumorigenic mechanism of TLR3 signaling, we injected poly(I: C) or phosphate-buffered saline intraperitoneally into an AOM/DSS-induced tumorigenesis model in WT mice. We also evaluate the direct antitumor effect of TLR signaling in AOM-treated WT and TLR3−/− mice without DSS. TLR3 deficiency increased tumor burden and colitis severity in the colon tissue than in the WT mice. β-catenin immunoreactivity was higher in TLR3−/− mice, while phospho-IκB kinase expression was similar. TLR3 activation by poly(I: C) did not reduce tumor burden in WT mice, but long-term AOM administration without DSS significantly increased tumor burden in TLR3−/− mice. TLR3 signaling attenuates CAC development, suggesting it may be a target for preventing CAC in inflammatory bowel disease.

Abstract Rational reforming of metal oxide has a potential importance to modulate their inherent properties toward appealing characteristics for various applications. Here, we present a detailed fundamental study of the proton migration phenomena between mediums and propose the methodology for controllable metal oxide hydrogenation through galvanic reactions with metallic cation under ambient atmosphere. As a proof of concept for hydrogenation, we study the role of proton adoption on the structural properties of molybdenum trioxide, as a representative, and its impact on redox characteristics in Li-ion battery (LiB) systems using electrochemical experiments and first-principles calculation. The proton adoption contributes to a lattice rearrangement facilitating the faster Li-ion diffusion along the selected layered and mediates the diffusion pathway that promote the enhancements of high-rate performance and cyclic stability. Our work provides physicochemical insights of hydrogenations and underscores the viable approach for improving the redox characteristics of layered oxide materials.

Abstract Background Ambient humidity has a significant impact on respiratory health and influences disease and symptoms. However, large-scale studies are required to clarify its specific effects on lung function and respiratory symptoms. We examined the relationship between relative humidity (RH), lung function, and respiratory symptoms using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Methods In this cross-sectional study, we analyzed data from KNHANES participants aged ≥ 40 years, collected between 2016 and 2018. Pulmonary function tests (PFTs) and health questionnaires were used to assess lung function and respiratory symptoms. Individual environmental data, including RH, were obtained from the Community Multiscale Air Quality model and linked to the participants’ addresses. Short-term (0–14 days), mid-term (30–180 days), and long-term (1–5 years) RH exposures were examined. Linear regression models were used to evaluate the associations between RH and PFTs. Univariate and multivariable logistic regression models were applied to assess the risk of lung function abnormalities and respiratory symptoms. Results In total, 10,396 participants were included (mean age: 58.3 years, male: 43.6%). In multiple regression analysis, higher RH was negatively associated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio across various time lags, while FVC was positively correlated with long-term RH exposure. In multiple logistic analysis adjusted for clinical and environmental covariates, long-term higher RH exposure was associated with a lower risk of restrictive lung disease (odds ratio [OR] at 4-year moving average [MA]: 0.978, 95% confidence interval [CI]: 0.959–0.997), while mid-term RH exposure decreased the risk of chronic cough (OR at 90-day MA: 0.968, 95% CI: 0.948–0.987) and sputum production (OR at 90-day MA: 0.985, 95% CI: 0.969–1.001). Conclusions Higher RH was negatively associated with lung function and increased the risk of obstructive lung disease, whereas mid-term RH exposure reduced the risk of chronic cough and sputum production.

Abstract Background The tumor immune microenvironment, particularly tumor-infiltrating lymphocytes (TILs), plays a critical role in disease progression and treatment response in triple-negative breast cancers (TNBCs). This study was aimed to characterize the composition of TILs and investigate their clinicopathological and prognostic significance with a special focus on the spatial distribution of TILs in TNBCs. Methods We analyzed TNBC samples through PanCancer Immune Profiling using NanoString nCounter assays to identify immune-related genes that are expressed differentially in relation to TIL levels and evaluated protein expression of selected markers through immunohistochemical staining on tissue microarrays. For a comprehensive assessment of the expression of cytotoxic T lymphocyte (CTL) and natural killer (NK) cell markers, a CTL-NK score was devised based on CD8+, CD56+, CD57+, GNLY+, and GZMB+ TIL levels. Results Gene expression analysis revealed significant upregulation of CTL and NK cell-associated genes including GNLY, KLRC2, and GZMB in TIL-high TNBCs. Immunohistochemical validation confirmed that TNBCs with higher TILs had a greater amount of CD56+, CD57+, GNLY+, and GZMB+ TILs not only in absolute number but also in proportion relative to CD4+ or CD8+ TILs. High TIL and its subset (CD4+, CD8+, CD56+, CD57+, GNLY+, and GZMB+ TIL) infiltration correlated with favorable clinicopathological features of tumor. In survival analysis, high CTL-NK score was found to be an independent prognostic factor for better disease-free survival (DFS) of the patients. Furthermore, uniformly high TIL infiltration was linked to better DFS, whereas cases with heterogeneous TIL infiltration showed no difference in survival compared to those with uniformly low TIL infiltration. Conclusion Our study showed that CTL and NK cell-associated gene expression and protein levels differ significantly according to TIL levels and that CTL-NK score and distribution of TILs within tumors have a prognostic value. These findings emphasize the importance of CTLs and NK cells as well as the spatial uniformity of TIL infiltration in clinical outcome of TNBC patients, providing valuable insights for refining prognostic assessments and guiding immunotherapeutic strategies.

Purpose This study aimed to systematically evaluate the effectiveness of case-based learning (CBL) within a basic-clinical integrated educational program using the Context, Input, Process, and Product (CIPP) evaluation model. Methods The CBL program was integrated into the Pharmacology–Clinical Case Practice component of the pharmacology course, a mandatory course for first-year medical students. To evaluate the program, a CIPP model-based questionnaire was developed, assessing needs, goals, resources, educational management, and outcomes. To ensure the reliability and validity of the variables, factor analysis was performed, reducing an initial set of 28 items to 18 final observation variables distributed across four factors. The survey, designed to measure learner satisfaction, was administered to 37 students who participated in the Pharmacology–Clinical Case Practice course during the first semester of 2022. Results Participants rated their satisfaction with the CBL program based on the CIPP model (on a 5-point scale), giving an average score of 4.17. This suggests that learners who followed the CBL program combining basic and clinical components generally found the program operationally effective with positive outcomes. Conclusion The teaching model and evaluation model applied in this study can be utilized in various majors when operating CBL classes that link basic and clinical education in medical schools in the future.

ABSTRACT: This study investigated the potential of 2′-fucosyllactose (2′-FL) and galacto-oligosaccharides (GOS) combinations as a novel and cost-effective substitute for human milk oligosaccharides (HMO) in promoting gut health and reducing inflammation. In vitro studies using caco-2 cells showed that 2′-FL and GOS combinations (H1 = GOS:2′-FL ratio of 1.8:1; H2 = GOS:2′-FL ratio of 3.6:1) reduced LPS-induced inflammation by decreasing pro-inflammatory markers, whereas individual treatments had no significant effects. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, combined 2′-FL and GOS supplementation alleviated symptoms, improved gut permeability, and enhanced intestinal structure, with the GH1 group (H1 combo with DSS) being the most effective. 2′-Fucosyllactose and GOS combinations also enhanced short-chain fatty acid production in infant fecal batch fermentation and mouse fecal analysis, with GH1 showing the most promising results. The GH1 supplementation altered gut microbiota in mice with DSS-induced colitis, promoting microbial diversity and a more balanced Firmicutes to Bacteroidota ratio. Infant formula products (IFP) containing 2′-FL and GOS combinations (IFP2 = 174 mg of GOS and 95 mg of 2′-FL per 14 g serving, 1.8:1 ratio; IFP3 = 174 mg of GOS and 48 mg of 2′-FL per 14 g serving, 3.6:1 ratio) demonstrated gastrointestinal protective and anti-inflammatory properties in a co-culture model of caco-2 and THP-1 cells. These findings suggest that 2′-FL and GOS combinations have potential applications in advanced infant formulas and supplements to promote gut health and reduce inflammation.

For the peaceful use of nuclear energy, materials, and technology, various methods have been developed for safeguards purposes. Among them, the In-Situ Object Counting System has demonstrated its usefulness and reliability in various nuclear material verification activities, due to its capability of operating without standard materials. In the present study, the performance of In-Situ Object Counting System for uranium quantification was evaluated using an experimental drum at KEPCO NF as well as low-level radioactive waste drums at the Korea Radioactive Waste Agency. The results showed that In-Situ Object Counting System could quantify uranium in radioactive waste drums, with a relative error ranging from −1 to −67 % compared with destructive assay results. This study also examined, using the Monte Carlo N-particle transport 6.2 code, the factors that affect uncertainty in uranium quantification: geometrical conditions, spectrum quality, heterogeneity, and the self-shielding effect. These findings could prove useful in efforts to optimize the In-Situ Object Counting System as a tool for nuclear material verification in the safeguards context.

Surface decontamination agents must effectively capture particle contaminants that have been deposited on surfaces. This ability is particularly important in scenarios involving nuclear fallout particles. In this technical note, the particle-capturing ability of a hydrogel, specifically, the polyvinyl alcohol-borax complex, was investigated as a potential decontamination agent for treating radioactively contaminated surface. For the assessment, simulated nuclear fallout particles, prepared by melting consolidation at 1200 °C followed by mechanical milling, were fixed on a stainless-steel substrate. The results demonstrated that the hydrogel effectively removed the simulated fallout particles from the surface. Even after only 1 min of contact time, the surface was left thoroughly clean, demonstrating the effectiveness of the polyvinyl alcohol-borax complex as a surface decontamination agent.

Pancreatic alpha amylase (P-AMY) is used as a biomarker of acute pancreatitis (AP) in human medicine. To our knowledge, there are no studies evaluating the usefulness of P-AMY in dogs with AP. In this study, we evaluated the diagnostic value of P-AMY, currently not verified in veterinary medicine. The AP group (n = 40) consisted of dogs with AP diagnosed using clinical signs and laboratory examinations, including abnormal canine pancreatic lipase (cPL) concentration, and compatible abdominal ultrasound examination at first presentation. Evaluation of the canine AP severity (CAPS) score was performed. The control group (n = 38) was composed of normal dogs without any abnormalities in clinical findings, blood exams or diagnostic imaging. The correlation of P-AMY with cPL was confirmed by Pearson’s correlation analysis (r = 0.564, p

Unlike vertebrates, the number of toothed taxa in invertebrates is very few, with leeches being the only tooth-bearing organisms in the phylum Annelida. Copious studies have been conducted regarding vertebrate teeth; however, studies regarding the structure and function of invertebrate teeth are limited. In this study, the tooth structure of leeches, specifically Hirudo nipponia and Haemadipsa rjukjuana, was revealed, which showed sharp and pointed teeth along the apex of three jaws. Understanding conserved signaling regulations among analogous organs is crucial for uncovering the underlying mechanisms during organogenesis. Therefore, to shed light on the evolutionary perspective of odontogenesis to some extent, we conducted de novo transcriptome analyses using embryonic mouse tooth germs, Hirudo teeth, and Helobdella proboscises to identify conserved signaling molecules involved in tooth development. The selection criteria were particularly based on the presence of tooth-related genes in mice, Hirudo teeth, and Helobdella proboscis, wherein 4113 genes were commonly expressed in all three specimens. Furthermore, the chemical nature of leech teeth was also examined via TEM-EDS to compare the chemical composition with vertebrate teeth. The examination of tissue-specific genetic information and chemical nature between leeches and mice revealed chemical similarities between leech and mice teeth, as well as conserved signaling molecules involved in tooth formation, including Ptpro, Prickle2, and Wnt16. Based on our findings, we propose that leech teeth express signaling molecules conserved in mice and these conserved tooth-specific signaling for dental hard tissue formation in mice would corresponds to the structural formation of the toothed jaw in leeches.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 μg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley – signalling pathways – targets – metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs (Eubacterium limosum, Eggerthella sp. SDG-2, Alistipes indistinctus YIT 12060, Odoribacter laneus YIT 12061, Paraprevotella clara YIT 11840, Paraprevotella xylaniphila YIT 11841) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.

Burn injuries, affecting local skin disruption as well as inducing systemic inflammatory responses, are presented as a global public health problem. To enhance the effects of burn wound healing, treatment must simultaneously regulate both re-epithelialization and hyperinflammation. Extracts of Sargassum horneri (S. horneri) have shown a potential to enhance skin wound healing through antioxidative properties, immune enhancement, and modulation of inflammatory responses. However, despite its promising application for burn wound healing, specific investigation into S. horneri-derived compounds for enhancing wound healing has not yet been conducted. In this research, we investigated the burn wound-healing effect of the low-temperature pulverization-specific S. horneri extract (LPSHE), which could not be detected using the room-temperature grinding method. In a mouse burn model with third-degree burn injuries, LPSHE accelerated re-epithelialization by promoting the increase in F-actin formation and reduced burn-induced ROS levels. Additionally, LPSHE significantly regulated hyperinflammation by reducing pro-inflammatory cytokines. Further investigation into molecular mechanisms using HaCaT keratinocytes also demonstrated beneficial effects on burn wound healing. Taken together, our findings suggested that LPSHE is a promising therapeutic candidate for enhancing burn wound healing. Furthermore, this research underscored the importance of low-temperature pulverization in discovering novel natural compounds from marine organisms.

Numerous studies have explored the welfare rearing conditions of broilers; however, studies on the level of metabolisable energy (ME) in feed, which is a key factor in broiler growth, are lacking. Accordingly, this study investigated the appropriate ME levels for broilers under welfare rearing environments. A total of 980 one-day-old male chickens (Ross 308) were allocated to each group according to the environment and dietary ME as follows: conventional environment fed a standard ME program (conventional control; CC), welfare environment with a standard ME (welfare control; WC) and welfare groups with 200 kcal/kg lower (WL200), 100 kcal/kg lower (WL100), 100 kcal/kg higher (WH100) and 200 kcal/kg higher (WH200) than standard ME. The experiment lasted 5 weeks. The productivity, meat quality, blood and intestinal characteristics, nutrient digestibility and welfare indicators were analysed, whose results are as follows: WH200 had the highest body weight and low feed conversion ratio, whereas CC had the lowest feed intake (p