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Micronutrient deficiencies are common in inflammatory bowel disease (IBD). The aim of this study was to evaluate micronutrient deficiencies and identify muscular status of patients with IBD. From June 2019 to October 2021, a total of 105 patients with IBD were enrolled prospectively. To obtain objective data, micronutrients were measured in the patients' serum, and body composition analysis was performed using bioelectrical impedance analysis. There were 51 patients with ulcerative colitis (UC) and 54 with Crohn's disease (CD), while the gender ratio (M: F) was 54:51. The average age was 37 ± 18 years, which was significantly lower in patients with CD than UC (29 ± 16 vs. 45 ± 16, p < 0.001). Iron and magnesium were lower in patients with CD compared to UC, respectively (63.3 ± 42.5 vs. 82.8 ± 44.0 µg/dL, p = 0.024, 2.08 ± 0.15 vs. 2.15 ± 0.19 mg/dL, p = 0.036). Vitamin D levels showed insufficiency in patients with UC and deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567). In the UC and CD patient groups, skeletal muscle index (SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC (SMI: 32.8 ± 4.7 vs. 35.8 ± 5.5%, p < 0.004, adjusted skeletal muscle: 7.0 ± 1.5 vs. 8.2 ± 1.9 kg/m 2 , p < 0.001). In conclusion, decreased trace elements, specifically iron, magnesium, and vitamin D, as well as skeletal muscle mass were observed to be prominent in patients with CD as compared to UC.

In cooperative multi-agent reinforcement learning, agents jointly optimize a centralized value function based on the rewards shared by all agents and learn decentralized policies through value function decomposition. Although such a learning framework is considered effective, estimating individual contribution from the rewards, which is essential for learning highly cooperative behaviors, is difficult. In addition, it becomes more challenging when reinforcement and punishment, help in increasing or decreasing the specific behaviors of agents, coexist because the processes of maximizing reinforcement and minimizing punishment can often conflict in practice. This study proposes a novel exploration scheme called multi-agent decomposed reward-based exploration (MuDE), which preferably explores the action spaces associated with positive sub-rewards based on a modified reward decomposition scheme, thus effectively exploring action spaces not reachable by existing exploration schemes. We evaluate MuDE with a challenging set of StarCraft II micromanagement and modified predator-prey tasks extended to include reinforcement and punishment. The results show that MuDE accurately estimates sub-rewards and outperforms state-of-the-art approaches in both convergence speed and win rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Byunghyun Yoo has patent pending to Electronics and Telecommunicatons esearch Insttute., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The combined effects of the novel antifouling biocide tralopyril (TP) nitrile and ocean acidification (OA) on marine organisms are still not well understood, despite the increasing attention given to the toxic effects of emerging pollutants and OA on marine organisms in recent years. In this study, Crassostrea gigas (C. gigas) was exposed to TP, OA, and a combination of TP and OA for 21 days with a 14-day depuration. This study investigated the inter-tissue variability in energy metabolism responses and the impacts on gonadal development in C. gigas under both single and combined exposures to TP and OA. The results indicate that TP exposure and OA resulted in up-regulation of energy metabolism genes in the C. gigas, with tissues exhibiting enhanced aerobic metabolism. Furthermore, OA influences the sex determination of C. gigas, promoting the development of female individuals. Moreover, following depuration, C. gigas is able to restore normal energy metabolism and sexual development through the accumulation of suitable energy reserves. This study provides a valuable reference for the environmental and ecological risk assessment of TP, addressing the research gap in understanding the combined toxicity of TP and OA on aquatic organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/aims: Chicago classification version 4.0 enhances the diagnosis of esophageal motility disorders using position change and provocative tests such as multiple rapid swallows and a rapid drink challenge. This study investigates the diagnostic role of the rapid drink challenge based on Chicago classification 4.0 using a functional luminal imaging probe to estimate the cutoff value., Methods: This study included 570 patients who underwent esophageal manometry with a rapid drink challenge between January 2019 and October 2022. The diagnostic flow was analyzed according to Chicago classification 4.0., Results: Ninety-nine patients (38, achalasia; 11, esophagogastric junction outflow obstruction; 7, ineffective esophageal motility; 1, hypercontractile esophagus; and 42, normal esophageal function) failed the rapid drink challenge. Among the 453 participants, 50 and 86 were diagnosed with achalasia and esophagogastric junction outflow obstruction, respectively, using Chicago classification 4.0. In 249/453 (55.0%) patients initially diagnosed with esophagogastric junction outflow obstruction using Chicago classification 3.0, the diagnosis was changed to achalasia (n = 28), hypercontractile esophagus (n = 7), ineffective esophageal motility (n = 7), or normal esophageal function (n = 121) using Chicago classification 4.0. Rapid drink challenge-integrated relaxation pressure's diagnostic cutoff value was 19 mmHg. Nine patients had diagnoses changed after the rapid drink challenge, including 3 with panesophageal pressurization., Conclusions: Chicago classification 4.0 increased the diagnostic yield of the rapid drink challenge by 2.0% (9/453 patients). However, the rapid drink challenge had a failure rate of 17.9% (99/552 patients). Given the relatively low diagnostic yield and high failure rate of the rapid drink challenge, we recommend adopting an individualized approach to manometry.

Background/aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE. Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established. This study aims to establish these thresholds for the first time among Asian patients with EoE., Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 and November 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index., Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively ( P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology were available for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold (sensitivity, 0.95; specificity, 0.88; Youden index, 0.83)., Conclusions: The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3, respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Plasmopara viticola (Berk.et Curtis) Berl. Et de Toni is the pathogen that causes grape downy mildew, which is an airborne disease that severely affects grape yield and causes huge economic losses. The usage of effective control methods can reduce the damage to plants induced by grape downy mildew. Biocontrol has been widely used to control plant diseases due to its advantages of environmental friendliness and sustainability. However, to date, only a few comprehensive reviews on the biocontrol of grape downy mildew have been reported. In this review, we summarize the biological characteristics of P. viticola and its infection cycle, followed by a detailed overview of current biocontrol agents, including bacteria and fungi that could be used to control grape downy mildew, and their control effects. Furthermore, potential control mechanisms of biocontrol agents against grape downy mildew are discussed. Lastly, suggestions for future research on the biocontrol of grape downy mildew are provided. This review provides the basis for the application of grape downy mildew biocontrol.

Background and Objectives : Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods : Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results : The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions : In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations.

Background: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery., Patients and Methods: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model., Results: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%., Conclusions: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment., (© 2024. Society of Surgical Oncology.)

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Oral lichen planus (OLP) is a chronic inflammatory disease characterized by an intensive infiltration of cytotoxic T cells, which causes keratinocyte death. Abnormal changes within keratinocytes might be critical for OLP onset and progression, but the pathogenic mechanism of OLP is still uncertain. The human oral microbiota, consisting of approximately 50-100 billion bacterial entities, encompasses around 200 dominant bacterial species. These bacteria continuously produce and release extracellular vesicles (EVs), which play a significant role in host-microbe interactions. However, the impact of these bacterial EVs on the progression of OLP has not been fully elucidated. In this study, through comprehensive database analysis and experimental validation, we observed that OLP lesions exhibit elevated inflammatory signatures and significantly increased phosphorylation of STAT3 compared to non-OLP tissues. Notably, EVs derived from key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were shown to induce an inflammatory response and activate STAT3 signaling pathways, closely mirroring the pathophysiological features observed in OLP. These results underscore the potential role of bacterial EVs in the pathogenesis of OLP and highlight STAT3 as a critical mediator in this process., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.

Background: The increasing population of cancer survivors poses a significant challenge for healthcare systems globally, necessitating comprehensive post-treatment care to address diverse physical, psychological, and social needs., Objective: This systematic review aims to synthesize and critically evaluate the current evidence concerning the unmet needs for nursing services among cancer survivors, spanning various dimensions of survivorship care., Methods: A systematic search was conducted across major databases, including PubMed, CINAHL, and PsycINFO, to identify relevant studies investigating the unmet needs and health-related quality-of-life (HRQOL) of nursing services led by nurses among cancer survivors. The final search update was conducted in June 2024. Unmet needs dimensions were categorized by the biopsychosocial-spiritual framework., Results: Of the 9503 records searched, 18 studies were included. This review revealed mixed findings in the domains of unmet needs and interventions aimed at addressing them. While nurse-led interventions showed promise in addressing physical and daily living needs, outcomes related to psychological and emotional needs varied across studies. Additionally, nurse-led interventions were effective in addressing patient-clinician communication and health system/information needs, although statistical significance was not consistently observed. HRQOL assessments using general and cancer-specific measures yielded mixed findings., Conclusions: Despite limitations of the risk of bias of included studies and weak study designs for evaluating nurse-led intervention effects for cancer survivors, the findings highlight the potential of nursing practice to significantly contribute to improving unmet needs of physical, psychological, and social perspectives and ultimately improving their HRQOL. However, the impact on the spiritual needs of nursing care services is limited by the low number of studies., Implications for Cancer Survivors: By providing comprehensive support and management, nursing practice can enhance post-treatment outcomes and HRQOL for cancer survivors, contributing to more patient-centered and effective care delivery. More rigorous research considering a biopsychosocial-spiritual perspective to help cancer survivors improve HRQOL is needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D ( KDM5D ), olfactory receptor 870 ( Olfr870 ), pancreatic lipase ( PNLIP ), and alkaline phosphatase intestinal ( ALPI ). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

G-protein-coupled receptor kinase 2 (GRK2) interacts with Gβγ and Gαq, subunits of G-protein alpha, to regulate cell signalling. The second messenger inositol trisphosphate, produced by activated Gαq, promotes calcium release from the endoplasmic reticulum (ER) and regulates maturation-promoting factor (MPF) activity. This study aimed to investigate the role of GRK2 in MPF activity during the meiotic maturation of porcine oocytes. A specific inhibitor of GRK2 (βi) was used in this study. The present study showed that GRK2 inhibition increased the percentage of oocyte arrest at the metaphase I (MI) stage (control: 13.84 ± 0.95%; βi: 31.30 ± 4.18%), which resulted in the reduction of the maturation rate (control: 80.36 ± 1.94%; βi: 65.40 ± 1.14%). The level of phospho-GRK2 decreased in the treated group, suggesting that GRK2 activity was reduced upon GRK2 inhibition. Furthermore, the addition of βi decreased Ca 2+ release from the ER. The protein levels of cyclin B and cyclin-dependent kinase 1 were higher in the treatment group than those in the control group, indicating that GRK2 inhibition prevented a decrease in MPF activity. Collectively, GRK2 inhibition induced meiotic arrest at the MI stage in porcine oocytes by preventing a decrease in MPF activity, suggesting that GRK2 is essential for oocyte meiotic maturation in pigs., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background/aim: Macrophages prevail in the microenvironment of several tumors, including non-small-cell lung cancer (NSCLC), where they secrete pro-tumorigenic factors that contribute to cancer progression. This study investigated the role of macrophages on the resistance of epidermal growth factor receptor (EGFR)-mutated NSCLC cells to tyrosine kinase inhibitors (TKIs)., Materials and Methods: EGFR-mutated cell lines PC-9 and HCC827 were cocultured with macrophages and treated with TKIs (erlotinib and gefitinib). The effects of the macrophage-conditioned medium (macrophage CM) on gefitinib resistance and cell migration were also evaluated., Results: Co-culture with macrophages significantly enhanced the resistance to erlotinib and gefitinib in PC-9 and HCC827 cells compared to that in cells cultured independently. Macrophage CM markedly induced gefitinib resistance in PC-9 cells, with maximum resistance observed at 50% CM concentration. This resistance persisted for up to 48 h post-CM removal. Macrophage CM inhibited gefitinib-induced apoptosis, as evidenced by the decreased expression of cleaved caspase-3, PARP, and BIM. Additionally, macrophage CM increased the migration ability of PC-9 cells, as shown by the wound healing and transwell migration assays. Studies have shown that TonEBP is crucial in cancer metastasis and drug resistance; we found that inhibition of TonEBP/NFAT5 expression reduced gefitinib resistance and migration in macrophage CM-induced PC-9 cells, indicating its role as mediator of these effects., Conclusion: Macrophages contribute to TKI resistance and enhance the migration of EGFR-mutated NSCLC cells through mechanisms involving TonEBP/NFAT5. Therefore, targeting TonEBP/NFAT5 represents a potential therapeutic strategy for overcoming macrophage-induced TKI resistance in NSCLC cells., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The present study tested 14-month-old monolingual infants (N = 64, 52% female, 75% Korean, and 25% American) in a looking-time task adapted from previous referent identification research. In three experiments, Korean-learning infants watched a speaker, who could only see one of two identical balls, ask a recipient, "gong jom jul-lae?" ("Will you give me Ø ball?" because Korean lacks an article system). They expected the recipient to reach for the ball visible to the speaker, but not the one hidden from her, only when the speaker was introduced separately to facilitate perspective-taking. Korean infants were also found to hold these expectations when the speaker said, "jeo gong jom jul-lae?" ("Will you give me that ball?"), presumably because the added demonstrative "jeo" rendered the speech more informative. A group of American English-learning infants performed similarly, but not as robustly as did their Korean peers, when the speaker requested "Give me that ball." These findings shed new light on how infants use their emergent perspective-taking and language skills to interpret a speaker's intended referent and expand the previous focus on English-learning infants., (© 2024 John Wiley & Sons Ltd.)

Methionine adenosyltransferase 2A (MAT2A) is an essential enzyme in the methionine cycle that generates S-adenosylmethionine (SAM) by reacting with methionine and ATP. SAM acts as a methyl donors for histone and DNA methylation, which plays key roles in zygotic genome activation (ZGA). However, the effects of MAT2A on porcine ZGA remain unclear. To investigate the function of MAT2A and its underlying mechanism in porcine ZGA, MAT2A was knocked down by double-stranded RNA injection at the 1-cell stage. MAT2A is highly expressed at every stage of porcine embryo development. The percentages of four-cell-stage embryos and blastocysts were lower in the MAT2A-knockdown (KD) group than in the control group. Notably, depletion of MAT2A decreased the levels of H3K4me2, H3K9me2/3, and H3K27me3 at the four-cell stage, whereas MAT2A KD reduced the transcriptional activity of ZGA genes. MAT2A KD decreased embryonic ectoderm development (EED) and enhancer of zeste homolog 2 (EZH2) expression. Exogenous SAM supplementation rescued histone methylation levels and developmental arrest induced by MAT2A KD. Additionally, MAT2A KD significantly increased DNA damage and apoptosis. In conclusion, MAT2A is involved in regulating transcriptional activity and is essential for regulating histone methylation during porcine ZGA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This paper presents an optimized design approach using nonlinear dynamic analysis and finite element methods to ensure the structural integrity of square-shaped containers made from ductile cast iron for intermediate- and low-level radioactive waste packaging. Ductile cast iron, with its spherical graphite structure, effectively distributes stress throughout the material, leading to a storage capacity increase of approximately 18%. Considering the critical need for containers that maintain integrity under extreme conditions like earthquakes, the design focuses on mitigating stress concentrations at the corners of square structures. Nonlinear dynamic analyses were conducted in five drop directions: three specified by ASTM-D5276 standards and two additional directions to account for different load patterns. Fractures were observed in four out of the five scenarios. For each direction where fractures occurred, equivalent loads causing similar displacement fields were applied to linear static models, which were then used for multi-load topology optimization. Three optimized models were derived, each increasing the volume by 1.4% to 1.6% compared to the original model, and the design that best met the structural integrity requirements during drop scenarios was selected. To further enhance the optimization process, weights were assigned to different load conditions based on numerical analysis results, balancing the impact of maximum stress, average stress, and plastic deformation energy. The final model, with its increased storage capacity and enhanced structural integrity, offers a practical solution for radioactive waste management, overcoming limitations in previous designs by effectively addressing complex load conditions.

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8 + T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer., (© 2024 Wiley‐VCH GmbH.)

Background and Aims: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection. Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence., Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. Of these patients, 112 without any information about Helicobacter pylori infection status, 164 who underwent APC for salvage therapy, 5 with high-grade dysplasia, and 12 with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed., Results: A total of 618 patients with LGD (median age, 64 years) were followed up for a median of 30 months, and local recurrence has happened in 21 (3.4%) patients. Multivariate analysis showed that lesion size (hazard ratio, 1.06; 95% confidential interval, 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 (2.6%) cases, and local recurrence was found in 7 (9.5%) cases of 109 tumors larger than 10 mm (P < .004)., Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of endoscopic resection. However, when a lesion is larger, APC should be selected carefully with close monitoring., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

Background: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer., Methods: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice., Results: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1., Conclusions: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer., (© 2024. The Author(s).)

Aim: The initial decrease in estimated glomerular filtration rate (eGFR), often known as the "initial dip," associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) is typically transient but may be more pronounced in older patients., Methods: We analyzed real-world data from 2,070 patients newly prescribed SGLT2i, tracking eGFR changes at baseline and 3, 6, 9, and 12 months after initiation. We defined a significant initial dip as over 10 % reduction in eGFR at 3 months. In addition, the 1-year change in eGFR after the initial decline was also assessed., Results: Of the total patients, 34.5 % were aged 60-69 years, 21.1 % were aged 70-79 years, and 11.5 % were aged 80 years or older. About 21.4 % experienced a significant dip at 3 months. The incidence of initial dip increases with age, with the highest incidence (38.7 %) in those aged 80 + . Despite the initial decline, subsequent eGFR was stable over one year in all age groups. Factors such as age, lower hemoglobin, higher uric acid levels, and use of RAS blockers were linked to the initial dip., Conclusions: Older patients showed a more pronounced initial eGFR decline after starting SGLT2i, but it stabilized for one year without further deterioration, similar to younger patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cathepsin B (CTSB) and inflammatory cytokines are critical in initiating and developing pancreatitis. Calcineurin, a central calcium (Ca 2+ )-responsive signaling molecule, mediates acinar cell death and inflammatory responses leading to pancreatitis. However, the detailed mechanisms for regulating CTSB activity and inflammatory cytokine production are unknown. Myricetin (MC) exhibits various biological activities, including anti-inflammatory effects. Here, we aimed to investigate MC effects on pancreatitis and the underlying mechanisms. Prophylactic and therapeutic MC treatment ameliorated the severity of cerulein-, L-arginine-, and PDL-induced acute pancreatitis (AP). The inhibition of CTSB activity by MC was mediated via decreased calcineurin activity and macrophage infiltration, not neutrophils infiltration, into the pancreas. Additionally, calcineurin activity inhibition by MC prevented the phosphorylation of Ca 2+ /CaM-dependent protein kinase kinase 2 (CaMKK2) during AP, resulting in the inhibition of CaMKIV phosphorylation and adenosine monophosphate-activated protein kinase (AMPK) dephosphorylation. Furthermore, MC reduced nuclear factor-κB activation by modulating the calcineurin-CaMKIV-IKKα/β-Iκ-Bα and calcineurin-AMPK-sirtuin1 axes, resulting in reduced production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Our results showed that MC alleviated AP severity by inhibiting acinar cell death and inflammatory responses, suggesting that MC as a calcineurin and CaMKK2 signaling modulator may be a potential treatment for AP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This paper presents a classification model for eye diseases utilizing attention mechanisms to learn features from fundus images and structures. The study focuses on diagnosing glaucoma by extracting retinal vessels and the optic disc from fundus images using a ResU-Net-based segmentation model and Hough Circle Transform, respectively. The extracted structures and preprocessed images were inputted into a CNN-based multi-input model for training. Comparative evaluations demonstrated that our model outperformed other research models in classifying glaucoma, even with a smaller dataset. Ablation studies confirmed that using attention mechanisms to learn fundus structures significantly enhanced performance. The study also highlighted the challenges in normal case classification due to potential feature degradation during structure extraction. Future research will focus on incorporating additional fundus structures such as the macula, refining extraction algorithms, and expanding the types of classified eye diseases.

Body odor is considered a diagnostic indicator of various infectious and chronic diseases. But, few studies have examined the odor markers for various toxic effects in the mammalian system. This study attempted to identify the novel diagnostic odor biomarkers for chemical-induced hepatotoxicity in animals. The changes in the concentration of odors were analyzed in the urine of Sprague Dawley (SD) rats treated with two dosages (100 or 200 mg/kg) of 1,2,3-trichloropropane (TCP) using gas chromatography-mass spectrometry (GC-MS). The TCP treatment induced significant toxicity, including a decrease in body weight, an increase in serum biochemical factors, and histopathological changes in the liver of SD rats. During this hepatotoxicity, the concentrations of six odors (ethyl alcohol, acrolein (2-propenal), methanesulfonyl chloride, methyl ethyl ketone, cyclotrisiloxane, and 2-heptanone) in urine changed significantly after the TCP treatment. Among them, acrolein, an acrid and pungent compound, showed the highest rate of increase in the TCP-treated group compared to the Vehicle-treated group. In addition, this increase in acrolein was accompanied by enhanced spermine oxidase (SMOX) expression, an acrolein metabolic enzyme, and the increased level of IL-6 transcription as a regulator factor that induces SMOX production. The correlation between acrolein and other parameters was conformed using correlagram analyses. These results provide scientific evidence that acrolein have potential as a novel diagnostic odor biomarker for TCP-induced hepatotoxicity., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00253-0., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood with putative links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures. We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and subgingival plaque samples from JDM probands (n = 28). To control for genetic and environmental determinants of microbiome community structure, we also profiled microbiomes of unaffected family members (n = 27 siblings, n = 26 mothers, and n = 17 fathers). Sample type (oral-vs-fecal) and nuclear family unit were the predominant variables explaining variance in microbiome diversity, more so than having a diagnosis of JDM. The oral and gut microbiomes of JDM probands were more similar to their own unaffected siblings than they were to the microbiomes of other JDM probands. In a sibling-paired within-family analysis, several potentially immunomodulatory bacterial taxa were differentially abundant in the microbiomes of JDM probands compared to their unaffected siblings, including Faecalibacterium (gut) and Streptococcus (oral cavity). While microbiome features of JDM are often shared by unaffected family members, the loss or gain of specific fecal and oral bacteria may play a role in disease pathogenesis or be secondary to immune dysfunction in susceptible individuals., (© 2024. The Author(s).)

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy., Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort., Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively., Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued., Competing Interests: We have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H 2 O 2 -induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems., (© 2024. The Author(s).)

Background: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia., Methods: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm 3 , and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis., Results: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001)., Conclusions: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations., Methods: Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated., Results: Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7-111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7-51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016)., Conclusion: While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Children autonomously make sound moral judgments based on internal criteria, but they tend to make erroneous judgments in the presence of social influences, and the reasons for these errors are not well understood. Thus, the current research investigated how the presence of observers who can see and listen to 3-year-old children's judgments but who do not present their opinions influences children's conformity in moral judgment behavior. In Experiment 1, the children ( N  = 30) were presented with pictures depicting prosocial behaviors and asked whether the behaviors were acceptable. The children's tendency to change their answers after hearing the counterintuitive opinions of informants was then measured. The results showed that the children's moral judgments were more likely to conform to that of the group in the presence of observers. Experiment 2 aimed to determine the reason children were more likely to conform to a group when being watched by observers in Experiment 1. Children ( N  = 30) were randomly assigned to two conditions with different observer conditions as follows. Observers were either wearing headsets, indicating that they could not hear the children's responses, or had them hanging around their necks, indicating that they could. The results showed that children's conformity behavior depended on whether observers could hear what they were saying. The current findings are expected to help elucidate not only social factors that affect children's moral judgments but also the developmental mechanism of an observer effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee and Song.)

The active form of the murine urokinase-type plasminogen activator (muPA) is formed by a 27-residue disordered light chain connecting the amino-terminal fragment (ATF) with the serine protease domain. The two chains are tethered by a disulfide bond between C1 CT in the disordered light chain and C122 CT in the protease domain. Previous work showed that the presence of the disordered light chain affected the inhibition of the protease domain by antibodies. Here we show that the disordered light chain induced a 3.7-fold increase in k cat of the protease domain of muPA. In addition, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and accelerated molecular dynamics (AMD) were performed to identify the interactions between the disordered light chain and the protease domain. HDX-MS revealed that the light chain is contacting the 110s, the turn between the β10- and β11-strand, and the β7-strand. A reduction in deuterium uptake was also observed in the activation loop, the 140s loop and the 220s loop, which forms the S1-specificty pocket where the substrate binds. These loops are further away from where the light chain seems to be interacting with the protease domain. Our results suggest that the light chain most likely increases the activity of muPA by allosterically favoring conformations in which the specificity pocket is formed. We propose a model by which the allostery would be transmitted through the β-strands of the β-barrels to the loops on the other side of the protease domain.

Background/aims: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. In this study, we examined the role and feasibility of clip-and-cut procedures (clip-and-cut endoscopic full-thickness resection [cc-EFTR]) for gastric GISTs., Methods: Medical records of 83 patients diagnosed with GISTs after endoscopic resection between 2005 and 2021 were retrospectively reviewed. Moreover, clinical characteristics and outcomes were analyzed., Results: Endoscopic submucosal dissection (ESD) and cc-EFTR were performed in 51 and 32 patients, respectively. The GISTs were detected in the upper third of the stomach for ESD (52.9%) and cc-EFTR (90.6%). Within the cc-EFTR group, a majority of GISTs were located in the deep muscularis propria or serosal layer, accounting for 96.9%, as opposed to those in the ESD group (45.1%). The R0 resection rates were 51.0% and 84.4% in the ESD and cc-EFTR groups, respectively. Seven (8.4%) patients required surgical treatment (six patients underwent ESD and one underwent cc-EFTR,) due to residual tumor (n=5) and post-procedure adverse events (n=2). Patients undergoing R0 or R1 resection did not experience recurrence during a median 14-month follow-up period, except for one patient in the ESD group., Conclusions: cc-EFTR displayed a high R0 resection rate; therefore, it is a safe and effective therapeutic option for small gastric GISTs.

Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas., Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection., Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma., Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection., Methods: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set., Results: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed., Conclusion: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Background and Objectives : Tacrolimus is a macrolide lactone compound derived from the bacterium Streptomyces tsukubensis , widely known as an immunosuppressant. In basic research, the effects of tacrolimus on osteogenic differentiation have been tested using mesenchymal stem cells. In this study, tacrolimus's effects on the cellular survival and osteogenic differentiation of stem cell spheroids were investigated. Materials and Methods : Concave microwells were used to form stem cell spheroids in the presence of tacrolimus at final concentrations of 0 μg/mL, 0.1 μg/mL, 1 μg/mL, 10 μg/mL, and 100 μg/mL. A microscope was used to test cellular vitality qualitatively, and an assay kit based on water-soluble tetrazolium salt was used to measure cellular viability quantitatively. Alkaline phosphatase activity and an anthraquinone dye test for measuring calcium deposits were used to assess osteogenic differentiation. To assess the expression of osteogenic differentiation, a quantitative polymerase chain reaction, Western blot, and RNA sequencing were performed. Results : Spheroids across all concentrations maintained a relatively uniform and spherical shape. Cell viability assay indicated that tacrolimus, up to a concentration of 100 μg/mL, did not significantly impair cell viability within spheroids cultured in osteogenic media. The increase in calcium deposition, particularly at lower concentrations of tacrolimus, points toward an enhancement in osteogenic differentiation. There was an increase in COL1A1 expression across all tacrolimus concentrations, as evidenced by the elevated mean and median values, which may indicate enhanced osteogenic activity. Conclusions : This study showed that tacrolimus does not significantly impact the viability of stem cell spheroids in osteogenic media, even at high concentrations. It also suggests that tacrolimus may enhance osteogenic differentiation, as indicated by increased calcium deposition and COL1A1 expression. These findings advance our understanding of tacrolimus's potential roles in tissue repair, regeneration, and stem cell-based therapeutic applications.

Aims: This study aimed to examine the relationship between heart failure knowledge, self-efficacy, social support, grit and self-care behaviour in patients with heart failure and to identify factors associated with patients' self-care behaviour., Background: Most patients with heart failure are not as active in implementing self-care behavioural practices as recommended by the guidelines., Design: This descriptive cross-sectional study was designed based on Bandura's Social Cognitive Theory., Methods: This study included 138 patients who were diagnosed with heart failure in an outpatient department of cardiology at a tertiary hospital in Korea. Data were collected between July and October 2020 using a structured questionnaire and electronic medical records. Data were analysed using the SPSS/WIN 27.0 program., Results: Grit had the strongest association with self-care behaviour among patients with heart failure, followed by social support, self-efficacy and heart failure knowledge. These variables accounted for approximately 52% of the variance in self-care behaviour., Conclusions: Health-care professionals should assess patients' grit and develop patient-tailored grit enhancement programmes. Based on the social cognitive theory, nursing intervention programmes that can simultaneously manage cognitive (knowledge and self-efficacy), social and environmental (social support) and behavioural support (grit) factors should be developed and applied to nursing practices to promote self-care., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results., Methods: We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol., Key Results: Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 m m 2 mmHg - 1 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration., Conclusions & Inferences: A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM., (© 2024 John Wiley & Sons Ltd.)

Although many epidemiological surveys for patients with psoriasis have been reported based on individual countries or facilities, there has been no study encompassing the major countries or the region in Asia. The Asian Society for Psoriasis (ASP) has been conducting an epidemiological study across various Asian countries and regions to elucidate the and compare the epidemiology of psoriasis. A total of 1948 cases were analyzed, with 938 cases from Japan, 530 cases from China, 325 cases from Korea, 141 cases from Chinese Taipei, and 14 cases from Thailand, all of which were enrolled between 2020 and 2022. In the Asian region total, the male-female ratio was 1.87:1 and the peak age at disease onset was 20-29 years. The proportion of psoriasis vulgaris (PsV), psoriatic arthritis (PsA), and pustular psoriasis (PP) was 80.1%, 17.7%, and 2.2%, respectively, and PsA was more commonly associated with nail symptoms than psoriasis vulgaris (PsV). Of the patients, 13% had a familial history of psoriasis and the most frequently affected family member was the father. Regarding treatment, 78.3% of the patients received topical medications, 9.0% underwent phototherapy, 34.0% received oral medications, and 36.1% were treated with biological agents. This study provided valuable information on the epidemiology and treatment of psoriasis using the registry data collected with the common reporting form in the same period in major Asian countries and regions. Male predominance is a distinctive feature of psoriasis in Asia. This epidemiological data registry in the ASP will continue afterwards., (© 2024 Japanese Dermatological Association.)

Objectives: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of " qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients., Methods: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD)., Results: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group ( P <0.05), and the multiple acupoints group was superior to the double acupoints group ( P <0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter ( P <0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group ( P <0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased ( P <0.05) while SDNN and RMSSD were increased ( P <0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups ( P <0.05)., Conclusions: TEAS treatment based on the theory of " qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.

Background: This work aimed to identify a method to achieve improved stone targeting and safety in shockwave lithotripsy by accounting for respiration., Methods: We set up an electromotive device simulating renal movement during respiration to place artificial stones within the phantom gel, measuring stone weight changes before and after shockwave exposure and the cavitation damage. We conducted clinical trials using respiratory masks and sensors to monitor and analyze patient respiration during shockwave lithotripsy., Results: The in vitro efficiency of lithotripsy was higher when adjusted for respiration than when respiration was not adjusted for. Slow respiration showed the best efficiency with higher hit rates when not adjusted for respiration. Cavitation damage was also lowest during slow respiration. The clinical study included 52 patients. Respiratory regularity was maintained above 90% in regular respiration. When respiration was regular, the lithotripsy rate was about 65.6%, which stayed at about 40% when respiration was irregular. During the lithotripsy, the participants experienced various events, such as sleep, taking off their masks, talking, movement, coughing, pain, nervousness, and hyperventilation. The generation of shockwaves based on respiratory regularity could reduce pain in patients., Conclusion: These results suggest a more accurate lithotripsy should be performed according to respiratory regularity., (© 2024. The Author(s).)

Multidrug-resistant (MDR) Salmonella enterica serovar Agona infections affect public health globally. This investigation aimed to ascertain the antimicrobial resistance profiles and molecular characteristics of Salmonella Agona isolates obtained from food-producing animals. A total of 209 Salmonella Agona isolates were recovered from mostly chickens (139 isolates), pigs (56 isolates), cattle (11 isolates), and ducks (3 isolates) between 2010 and 2020 in South Korea. In addition, these Salmonella Agona isolates were obtained from 25 slaughterhouses nationwide. Furthermore, this serotype suddenly increased in chickens in 2020. Salmonella Agona from chickens showed high resistance (69-83%) to ampicillin, streptomycin, tetracycline, trimethoprim/sulfamethoxazole, and chloramphenicol. Moreover, chicken/duck isolates (83.1%) showed significantly higher levels of MDR than cattle/pig isolates (1.5%). For molecular analysis by pulsed-field gel electrophoresis, infrared spectroscopy biotyping, and multilocus sequence typing in combination, a total of 23 types were observed. Especially two major types, P1-III-2-13 and P1-IV-2-13, comprised 59.3% of the total isolates spreading in most farms. Moreover, Salmonella Agona sequence type (ST)13 was predominant (96.7%) among three different STs (ST13, ST11, and ST292) widely detected in chickens (94.3%) in most farms located nationwide. Taken together, MDR Salmonella Agona in chickens might pose a potential risk to public health through direct contact or the food chain.

Background: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells., Results: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells., Conclusions: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate age-stratified radiographic features in temporomandibular joint osteoarthritis using cone-beam computed tomography., Materials and Methods: In total, 210 joints from 183 patients (144 females, 39 males, ranging from 12 to 88 years old with a mean age of 44.75±19.97 years) diagnosed with temporomandibular joint osteoarthritis were stratified by age. Mandibular condyle position and bony changes (flattening, erosion, osteophytes, subchondral sclerosis, and subchondral pseudocysts in both the condyle and articular eminence, thickening of the glenoid fossa, joint space narrowing, and joint loose bodies) were evaluated through cone-beam computed tomography. After adjusting for sex, the association between age groups and radiographic findings was analyzed using both a multiple regression model and a multinomial logistic regression model (α=0.05)., Results: The prevalence of joint space narrowing and protruded condyle position in the glenoid fossa significantly increased with age ( P <0.05). The risks of bony changes, including osteophytes and subchondral pseudocysts in the condyle; flattening, erosion, osteophyte, and subchondral sclerosis in the articular eminence; joint loose bodies; and thickening of the glenoid fossa, also significantly rose with increasing age ( P <0.05). The number of radiographic findings increased with age; in particular, the increase was more pronounced in the temporal bone than in the mandibular condyle ( P <0.05)., Conclusion: Increasing age was associated with a higher frequency and greater diversity of bony changes in the temporal bone, as well as a protruded condyle position in the glenoid fossa, resulting in noticeable joint space narrowing in temporomandibular joint osteoarthritis., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)

Purpose: The increased use of proton pump inhibitors (PPIs) in the elderly has raised concerns about potential severe adverse effects. Our systematic review investigated the mortality associated with PPI use in elderly populations., Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for relevant publications until August 2022. We included randomized controlled trials (RCTs), quasi-RCTs, and observational studies on the association between proton pump inhibitors and mortality in the elderly. To estimate the pooled relative risk (RR) and 95% confidence interval (CI), the inverse-variance random effect model was used. Heterogeneity was assessed using the I 2 test. Subgroup analyses were performed by follow-up period, population, and study design., Results: A total of 4 RCTs and 36 cohort studies were included in the meta-analysis. Four RCTs showed that there was no significant association between PPIs and the risk of death. From 23 observational studies (26 cohorts), the use of proton pump inhibitors was not significantly associated with increased mortality in the elderly (RR 1.14; 95% CI, 0.90-1.45). However, when controlling for covariates from 33 observational studies (41 cohorts), proton pump inhibitors in older adults aged 50 years or more were significantly associated with a 15% higher risk of mortality compared to nonusers (RR 1.15; 95% CI, 1.10-1.20)., Conclusions: Our meta-analysis of RCTs found that PPIs did not show a significant association with increased mortality risk in older adults. However, the meta-analysis of cohort studies and long-term follow-up studies showed a higher increased risk of death with PPI use in older adults. The prescription of PPIs in patients aged 50 years or older should be carefully considered., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The current research examined whether children's expectations about labeling conventions can be influenced by limited exposure to a foreign language. Three- to four-year-old Korean children were presented with two speakers who each assigned a novel label either in Korean or Spanish to a novel object. Children were asked whether both labels were acceptable for the object. Children who had more exposure to a foreign language through live social interaction, but not through media, were more likely to accept both Korean and Spanish labels. These findings indicate the influence of social interaction in foreign language exposure on children's understanding of different labeling conventions.

Background: Studies on the skin microbiome have been conducted to uncover the relationship between skin microbes and the host. However, most of these studies have primarily focused on analyzing individual microbial compositions, which has resulted in a limited understanding of the overall relationship., Methods: We analyzed the facial skin characteristics and microbial profiles of 100 healthy Korean female volunteers using the V1-V2 region of the 16S ribosomal RNA gene., Results: The two most prominent features of the facial skin microbiome, the proportion of Cutibacterium and α-diversity, were associated with most of the skin characteristics. Based on clustering results, we proposed four types of facial skin microbiome: type C for Cutibacterium, type B for balanced, type CB for those between types C and B, and type O for others. Type C, which has a high proportion of Cutibacterium, showed high levels of pigmentation, wrinkles, pores, and sagging pores, indicating a tendency for severe skin aging. Type B, which has no dominant species and high microbial diversity, had lower values for pigmentation and wrinkles indicating less severe skin aging. Type CB was an intermediate type between type C and type B in terms of microbial composition and the level of skin aging. Type O dominated by microorganisms other than Cutibacterium, had high levels of sebum and pores but low levels of wrinkles., Conclusion: We proposed a criterion for classifying facial skin microbial types, each of which showed distinct facial skin aging features. Our simplified microbial types will contribute to a better understanding of facial skin microbial studies., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: The Child and Adult Care Food Program (CACFP) provides reimbursement for meals and snacks offered in participating centers and issues nutrition standards, including guidelines for feeding infants in childcare settings. Offering training to childcare providers participating in the CACFP is necessary to ensure compliance with nutrition standards in childcare settings., Methods: A State Department of Education and University Extension system collaborated to develop an online nutrition training course for childcare providers. Providers (n = 57) participated in the course on CACFP nutrition standards related to feeding infants (0-12 months of age). Thirty-two of 57 participants completed both pre- and post-training surveys that were used to assess changes in knowledge and confidence concerning infant feeding standards. Paired t-tests and Wilcoxon signed-rank tests were conducted to assess differences in survey responses before and after the course., Results: Self-confidence and knowledge of providers related to infant feeding were significantly increased after completion of the training course (p < 0.001). More participants reported their sites were likely to respond to infants showing they were hungry or full than before the course (44.4% vs. 75.7%, respectively). Participant feedback indicated the online asynchronous course was convenient, useful, and topics were relevant to training needs., Discussion: The online course was feasible and effective for providing training on CACFP guidelines for childcare providers. Feedback from participants can be adapted and used for future training programs to further improve the course and delivery methods and efficiently reach a broad audience of childcare providers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)