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Sang-Jin Park,1,* Seung Ro Han,2,3,* Yun Hee Kang,2,3,* Eun-Jin Lee,1 Eu-Gene Kim,1 Hyobong Hong,4 Jae-Chan Jeong,4 Myung-Shin Lee,2,3 Seung-Hoon Lee,2,5 Dae-Yong Song1 1Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea; 2Eulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, Korea; 3Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Korea; 4Artifcial Intelligence Research Laboratory, Electronics and Telecommunications Research Institute (ETRI), Daejeon, Korea; 5Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea*These authors contributed equally to this workCorrespondence: Seung-Hoon Lee, Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1612, Fax +82-42-259-1669, Email nslsh@eulji.ac.kr Dae-Yong Song, Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1622, Fax +82-42-259-1669, Email dysong@eulji.ac.krPurpose: Magnetic particle imaging (MPI) is an emerging radiation-free, non-invasive three-dimensional tomographic technology that can visualize the concentrations of superparamagnetic iron oxide nanoparticles (SPIONs). To verify the applicability of the previously proposed point-of-care testing MPI (PoCT-MPI) in medical diagnosis and therapeutics, we imaged SPIONs in animal tumor models.Methods: CT26 or MC38 mouse colon carcinoma cells (2 × 106 cells) were subcutaneously injected into the right flank of BALB/c mice. SPIONs were either injected directly into the tumor lesions in the intratumoral group or through tail veins in the intravenous group. CT26 and MC38 tumor models were examined both intratumorally and intravenously to confirm the biological availability of SPIONs using PoCT-MPI.Results: Signals were observed in the tumor lesions from day 1 to day 7. This is the first study to successfully image the pathological region and show the biodistribution of SPIONs in CT26 tumor models using the recently developed PoCT-MPI technology. Furthermore, MC38 tumor models were examined, resulting in similar images to those of the CT26 tumor model in both intratumoral and intravenous groups.Conclusion: The present study demonstrates the biological applicability of PoCT-MPI, which promises to be a powerful diagnostic and therapeutic technique in biomedical imaging.Keywords: colon cancer, syngeneic mouse tumor model, point-of-care testing MPI, diagnostics

Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. KEY MESSAGES: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration., Competing Interests: Declarations. Ethics approval: All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Hallym University (hallym(2023–18)). Consent for publication: The informed consent was obtained from study participants. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism., Methods: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis., Results: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05)., Conclusions: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP., Competing Interests: Conflict of Interest. The authors declare no conflicts of interest., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The production of recombinant proteins in Escherichia coli is often challenged by cytoplasmic expression due to proteolytic degradation and inclusion body formation. Extracellular expression can overcome these problems by simplifying downstream processing and improving protein yields. This study aims to compare the efficiency of two Bacillus subtilis chitosanase signal peptides in mediating extracellular secretion in E. coli. We identified a naturally occurring mutant signal peptide (mCsn2-SP) from B. subtilis CH2 chitosanase (CH2CSN), which is characterized by a deletion of six amino acids in the N-region relative to the signal peptide (Csn1-SP) from B. subtilis CH1 chitosanase (CH1CSN). The CH1CSN and CH2CSN genes were cloned into the pET-11a vector and protein secretion was evaluated in E. coli BL21(DE3) host cells. Expression was induced with 0.1 mM and 1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) at 30 °C for one and three days. CH2CSN showed higher secretion levels compared to CH1CSN under all experimental conditions, especially with 0.1 mM IPTG induction for 3 days, which resulted in a 2.37-fold increase in secretion. Furthermore, it was demonstrated that mCsn2-SP is capable of secreting human Cu,Zn-superoxide dismutase (hSOD) in E. coli BL21(DE3) and successfully translocating it to the periplasmic region. This study represents the inaugural investigation into the utilisation of a naturally modified signal peptide, thereby corroborating the assertion that signal peptide deletion variants can influence protein secretion efficiency. Furthermore, the findings substantiate the proposition that such variants can serve as a viable alternative for the secretion of heterologous proteins in E. coli., Competing Interests: Declarations. Conflict of interest: The authors have no financial conflicts of interest to declare. Ethical statements: Not applicable., (© 2024. The Author(s).)

Background: Hepatic metastasis is the primary cause of colorectal cancer (CRC)-induced death. Our previous results showed the anti-metastatic effects of Coptidis rhizoma using in vitro model., Aim: The present study aimed to investigate whether berberine, the main active compound of C. rhizoma, inhibits colon-liver metastasis in an animal model, and to elucidate the underlying mechanisms., Methods: Murine colon carcinoma (CT26) tumor tissue was implanted into the cecum of balb/c mice with/without oral administration of berberine (100 mg/kg) for 21 days, after which liver metastasis was evaluated. In addition, the pharmacological actions of berberine were explored using 5-fluorouracil-resistant human colon cancer cells (HCT116/R)., Result: The administration of berberine significantly decreased the number of tumor nodules in the liver, while significant activation of E-cadherin (an epithelial marker), and suppression of vimentin, Snail and TGF-β (mesenchymal markers) were observed in primary colon tumor tissues. Berberine treatment also notably lowered the levels of inflammatory cytokines (TGF-β, TNF- α, IL-6 and IL-1β) in the blood. In HCT116/R cells, berberine significantly inhibited migration and invasion and modulated the expression of TGF-β and representative molecules related to its pathway. The results obtained with a TGF-β inhibitor (SB431542) and a TGF-β siRNA, strongly suggest that the mechanism of action of berberine is linked to TGF-β signaling., Conclusion: In conclusion, berberine evidently possess an anti-colon-liver metastatic effect, and its underlying mechanisms involve the inhibition of epithelial-mesenchymal transition (EMT) through the TGF-β signaling pathway. Thus, we cautiously propose the pharmacological potential of berberine in drug research studies targeting hepatic metastasis from CRC., Competing Interests: Declarations Ethics approval and consent to participate The animal study was reviewed and approved by Institutional Animal Care and Use Committee Daejeon University (DJUARB2022-002). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but debilitating disease characterized by a progressive necrosis of jaw bones in patients who have received anti-resorptive or anti-angiogenic therapies. Unfortunately, we still have no validated preventive or pharmaceutical interventions to help these patients, primarily due to our limited understanding of MRONJ pathogenesis. Here, we offer an extensive review of recent studies relevant to MRONJ pathogenesis. We present a hypothesis regarding the coupling of bone resorption and angiogenesis that relies on osteoblast-derived, matrix-bound vascular endothelial growth factors to explain why ONJ is associated with both anti-resorptive and anti-angiogenic agents., Methods: A narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports., Results: Reduced bone resorption leads to reduced angiogenesis, and vice versa, creating a vicious cycle that ultimately results in ischemic necrosis of the jaw. Additionally, we suggest that reduced angiogenesis, induced by anti-resorptive or anti-angiogenic agents, aggravates bacterial infection-induced bone necrosis, explaining why the jaw bone is particularly susceptible to necrosis., Conclusion: Our novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ., (© 2024 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.)

Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD 50 around 2.36 × 10 6 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments., 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.)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (3 d, 3 weeks, and 16 weeks) and treated with EMPA for 3 weeks (NFD, NFD + EMPA, HFD, HFD + EMPA; n = 5/group). EMPA regulated the expression of astrocyte markers and pro-inflammatory cytokine mRNA in the hypothalamus of HFD-induced mice, which was linked to regulation of the NF-κB pathway. Under hyperglycemic conditions, EMPA may mitigate hypothalamic inflammation by modulating astrocyte activation via the NF-κB pathway. Our findings demonstrated that EMPA possesses therapeutic potential beyond merely lowering blood glucose levels, opening new avenues for addressing inflammation and providing neuroprotection in metabolic disease management.

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon., Competing Interests: Declaration of competing interest The authors declare that they do not possess any personal relationships or competing financial interests that would impact the work reported in the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The fish processing industry generates a significant amount of waste, and the recycling of this waste is an issue of global concern. We sought to utilize the heads of cutlassfish (Trichiurus lepturus), which are typically discarded during processing, to produce peptone, which is an important source of amino acids for microbial growth and recombinant protein production. Cutlassfish head muscle (CHM) were isolated, and the optimal protease and reaction conditions for peptone production were determined. The resulting peptone contained 12.22 % total nitrogen and 3.19 % amino nitrogen, with an average molecular weight of 609 Da, indicating efficient hydrolysis of CHM. Growth assays using Escherichia coli have shown that cutlassfish head peptone (CP) supports similar or superior growth compared to other commercial peptones. In addition, when recombinant chitosanase from Bacillus subtilis and human superoxide dismutase were produced in E. coli, CP gave the highest expression levels among six commercial peptones tested. In addition, the expression levels of chitosanase and superoxide dismutase were 20 % and 32 % higher, respectively, in CP medium compared to the commonly used Luria-Bertani (LB) medium. This study demonstrates the potential of using cuttlassfish waste in the production of microbial media, thereby adding significant value to fish waste. The results contribute to sustainable waste management practices and open avenues for innovative uses of fish processing by-products in biotechnological applications., 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 the paper. The authors declared that they don't have competing interests on this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/objectives: Atherosclerosis particularly due to high circulating level of low-density lipoprotein is a major cause of cardiovascular diseases. Ellagic acid is a natural polyphenolic compound rich in pomegranates and berries. Our previous study showed that ellagic acid improved functionality of reverse cholesterol transport in murine model of atherosclerosis. The aim of this study is to investigate whether ellagic acid inhibited inflammation-associated atherosclerotic plaque formation in cholesterol-fed apolipoprotein E (apoE)-knockout (KO) mice., Materials/methods: Wild type mice and apoE-KO mice were fed a cholesterol-rich Paigen diet for 10 weeks to induce severe atherosclerosis. Concurrently, 10 mg/kg ellagic acid was orally administered to the apoE-KO mice. Plaque lesion formation and lipid deposition were examined by staining with hematoxylin and eosin, Sudan IV and oil red O., Results: The plasma leukocyte profile of cholesterol-fed mice was not altered by apoE deficiency. Oral administration of ellagic acid attenuated plaque lesion formation and lipid deposition in the aorta tree of apoE-KO mice. Ellagic acid substantially reduced plasma levels of soluble vascular cell adhesion molecule and interferon-γ in Paigen diet-fed apoE-KO mice. When 10 mg/kg ellagic acid was administered to cholesterol-fed apoE-KO mice, the levels of CD68 and MCP-1 were strongly reduced in aorta vessels. The protein expression level of nitric oxide synthase-2 (NOS2) in the aorta was highly enhanced by supplementation of ellagic acid to apoE-KO mice, but the expression level of heme oxygenase-1 (HO-1) in the aorta was reduced. Furthermore, ellagic acid diminished the increased aorta expression of the inflammatory adhesion molecules in cholesterol-fed apoE-KO mice. The treatment of ellagic acid inhibited the scavenger receptor-B1 expression in the aorta of apoE-KO mice, while the cholesterol efflux-related transporters were not significantly changed., Conclusion: These results suggest that ellagic acid may be an atheroprotective compound by attenuating apoE deficiency-induced vascular inflammation and reducing atherosclerotic plaque lesion formation., Competing Interests: Conflict of Interest: The authors declare that they have no potential conicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Vertical migration behaviour, which is integral to marine energy circulation, is a prevalent trait among marine organisms. However, the behaviour of phytoplankton, particularly beyond diel vertical migration (DVM), remain underexplored compared to groups like zooplankton. Through the lens of the harmful alga Heterosigma akashiwo, which exhibits active vertical migrations and unique fluctuating bloom dynamics, this study aimed to explore the ecological intricacies and diverse benefits of phytoplankton vertical migration behaviours. During the bloom period of H. akashiwo, we unexpectedly observed a dense concentration of cells at bottom layer during daytime. This phase coincided with the emergence of cells related to this species' sexual reproduction. Laboratory experiments further showed an elevated frequency of sexual reproduction in the cell populations that migrated to deeper depths compared to those at the surface. This finding implies a connection between dense bottom accumulation (BA) and the life cycle transitions of the species. This BA phase persisted for two days, after which the populations returned to their standard DVM behaviour, providing insight into the unique fluctuating bloom dynamics of H. akashiwo. Our study suggests that phytoplankton vertical migrations are not strictly dictated by DVM, revealing diverse vertical migration behaviours that may contribute to the complexity of harmful algal bloom patterns., 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 Inc. All rights reserved.)

Context: With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized., Objective: This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels., Methods: 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis., Results: At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG., Conclusion: Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Kimura's disease (KD) is a rare, chronic inflammatory disorder characterized by angiolymphoid hyperplasia, peripheral eosinophilia, and elevated serum immunoglobulin E levels. It primarily affects young Asian males and typically involves the head and neck region, especially near the mandible and postauricular regions. Orbital involvement is unusual and extraocular muscle (EOM) involvement is exceedingly rare, with only a few cases reported in the literature. The present report describes a case of surgically confirmed KD in a 16-year-old male, involving the bilateral EOM, lacrimal gland, and left parotid gland., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2024 The Korean Society of Radiology.)

Breast cancer (BrCa) remains a significant health concern globally, influenced by both nonmodifiable and modifiable risk factors. Limited studies have explored the role of color-specific vegetables and fruits, which are rich in specific phytonutrients, on BrCa risk. We hypothesized that consuming color-specific vegetables and fruits may decrease BrCa risk in Korean women. This case-control study examined the relationship between the intake of different-colored vegetables and fruits and the risk of BrCa, considering menopausal, hormone receptor status, tumor subtypes. We matched 395 patients and 395 controls by age and recruited from the National Cancer Center in Korea. Dietary data was collected via food frequency questionnaire, categorizing by colors: green, orange/yellow, red/purple, and white. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression models, with subgroup analyses for menopausal, hormone receptor status, and tumor subtypes. Results shown BrCa patients consumed less vegetables and fruits than control group. Higher consumption of green, other orange/yellow, and white vegetables and fruits was negatively associated with BrCa risk [OR (95% CIs) of Q4 vs Q1 = 0.59 (0.36-0.94); 0.55 (0.33-0.89); and 0.60 (0.37-0.96), respectively]. Particularly, a greater intake of dark green leafy vegetables was significantly associated with reduced BrCa risk (OR of Q4 vs Q1 = 0.55, 95% CI = 0.34-0.89). Subgroup analysis consistently demonstrated inverse associations between higher intake of green-color vegetables and fruits and BrCa risk. Our findings suggest that a diet rich in green and white-color vegetables and fruits may lower BrCa risk among Korean women., Competing Interests: Author declarations None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acupuncture has been proven effective for various types of pain, and peripheral molecular signals around acupuncture-treated areas have been suggested to contribute to the analgesic effects of acupuncture. However, the underlying mechanism from these peripheral molecular signals to central ones remains unclear. The purpose of this study was to investigate whether peripheral Rho-associated protein kinase (ROCK) activation induced by acupuncture treatment mediates acupuncture analgesia, and also to investigate the relationship between ROCK activation and extracellular signal-regulated kinase (ERK), which has previously been proven to mediate acupuncture analgesia and other related molecular changes during acupuncture., Methods: Acupuncture was treated at the bilateral GB34 acupoints of C57BL/6 mice, after which changes in ROCK activation and the location of its expression in the skin were analyzed. To verify the role of ROCK in acupuncture analgesia, we administrated ROCK inhibitor Y-27632 (0.3 μg/ul) into the skin before acupuncture treatment with formalin and complete Freund adjuvant (CFA) induced pain models, then the nociceptive responses were analyzed., Results: Acupuncture treatment produced ROCK2 activation in the skin after 30 and 60 min, and the histological analyses revealed that ROCK2 was activated in the fibroblast of the dermis. The acupuncture-induced ROCK2 expression was significantly attenuated by the ERK inhibitor, whereas phospho-ERK expression was not inhibited by ROCK inhibitor. In both the formalin- and CFA-induced mouse pain models, acupuncture analgesia was blocked by ROCK inhibitor administration., Conclusion: Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia., Competing Interests: The authors declare that there are no financial or other relationships that might lead to a conflict of interest., (© 2024 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Among inorganic thermoelectric materials, flexible thermoelectric materials have attracted considerable attention. In this study, highly flexible and plastically bendable silver selenide films with excellent thermoelectric performance at room temperature are presented. The flexibility of the freestanding silver selenide films was significantly improved through a simple annealing treatment. The highly flexible silver selenide films with a thickness of 26.0 μm displayed outstanding n-type thermoelectric performance, achieving an in-plane zT value of 0.38 at room temperature. Because silver selenide films are plastically bendable with a bending radius of less than 1 mm, they can be shaped into various forms. To achieve stretchability and skin-conformality in the thermoelectric generator, S-shaped silver selenide strips were used as an n-type thermoelectric element. Effective harvesting of electricity from heat of the human body was successfully demonstrated.

Obstructive sleep apnea is characterized by a decrease or cessation of breathing due to repetitive closure of the upper airway during sleep, leading to a decrease in blood oxygen saturation. In this study, employing a U-Net model, we utilized drug-induced sleep endoscopy images to segment the major causes of airway obstruction, including the epiglottis, oropharynx lateral walls, and tongue base. The evaluation metrics included sensitivity, specificity, accuracy, and Dice score, with airway sensitivity at 0.93 (± 0.06), specificity at 0.96 (± 0.01), accuracy at 0.95 (± 0.01), and Dice score at 0.84 (± 0.03), indicating overall high performance. The results indicate the potential for artificial intelligence (AI)-driven automatic interpretation of sleep disorder diagnosis, with implications for standardizing medical procedures and improving healthcare services. The study suggests that advancements in AI technology hold promise for enhancing diagnostic accuracy and treatment efficacy in sleep and respiratory disorders, fostering competitiveness in the medical AI market., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

We propose a scheme for chirality discrimination via a topological invariant. The physical model is based on a three-level subspace of a molecule. By modulating the components of the control field with proper frequencies, two different two-level effective Hamiltonians are derived for the left-handed and the right-handed molecules. We parameterize the effective Hamiltonians with two angles and demonstrate that a topological quantum phase transition can be induced by tuning the effective Rabi frequency if the molecule is right-handed. This phenomenon provides a method to discriminate the chirality of the molecule by measuring a topological invariant, i.e., the Chern number, of the parametric manifold. Since the Chern number is robust against perturbations to the system, the scheme is insensitive to the systematic errors of the control fields, the deviations of the modulation frequencies, and decoherence of the molecule. Therefore, the scheme may provide useful perspectives to construct a robust discriminator of chiral molecules.

The association between dietary carotenoids and breast cancer (BC) risks were inconsistent. Therefore, this study investigated the association between dietary carotenoid and BC risks among Korean women. We recruited participants from the National Cancer Centre of Korea. Odds ratios and 95% confidence intervals were calculated with a logistic regression model. There was an inverse association between dietary carotenoid subclasses and BC risks; in particular, a higher intake of β-carotene and lutein/zeaxanthin was associated with reduced BC risks. After subgroup analysis with estrogen receptor (ER)/progesterone receptor (PR) status, there was similar trend among ER-/PR- women. We further investigated which foods contribute to the carotenoid intake. A higher intake of radish leaves, kale, and bracken was associated with lowered BC risks. Accordingly, dietary carotenoid, particularly β-carotene and lutein/zeaxanthin, appears to be associated with a lower risk of BC among Korean women.

Loss of the inner blood-retinal barrier (BRB) integrity is a main feature of ocular diseases such as diabetic macular edema. However, there is a lack of clarity on how inner BRB function is modulated within the diabetic retina. The current study examined whether eucalyptol inhibited inner BRB destruction and aberrant retinal angiogenesis in 33 mM glucose-exposed human retinal microvascular endothelial (RVE) cells and db/db mice. This study further examined the molecular mechanisms underlying endothelial dysfunction including retinal endoplasmic reticulum (ER) stress and angiopoietin (Ang)/Tie axis in conjunction with vascular endothelial growth factor (VEGF). Eucalyptol is a naturally occurring monoterpenoid and an achiral aromatic component of many plants including eucalyptus leaves. Nontoxic eucalyptol reduced the production of amyloid-β (Aβ) protein in glucose-loaded RVE cells and in diabetic mice. This natural compound blocked apoptosis of Aβ-exposed RVE cells in diabetic mouse eyes by targeting ER stress via the inhibition of PERK-eIF2α-ATF4-CHOP signaling. Eucalyptol promoted activation of the Ang-1/Tie-2 pathway and dual inhibition of Ang-2/VEGF in Aβ-exposed RVE cells and in diabetic eyes. Supply of eucalyptol reversed the induction of junction proteins in glucose/Aβ-exposed RVE cells within the retina and reduced permeability. In addition, oral administration of eucalyptol reduced vascular leaks in diabetic retinal vessels. Taken together, these findings clearly show that eucalyptol inhibits glucose-induced Aβ-mediated ER stress and manipulates Ang signaling in diabetic retinal vessels, which ultimately blocks abnormal angiogenesis and loss of inner BRB integrity. Therefore, eucalyptol provides new treatment strategies for diabetes-associated RVE defects through modulating diverse therapeutic targets including ER stress, Ang-1/Tie-2 signaling, and Ang-2/VEGF.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 μL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide ( AgRP ) and pro-opiomelanocortin ( POMC ) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP . These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.

The classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator, including immune complexes. Factor H is regarded as the key downregulatory protein of the complement alternative pathway. However, both C1q and factor H bind to target surfaces via charge distribution patterns. For a few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation through such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are known to recognize foreign or altered-self materials, e.g., bacteria, viruses, and apoptotic/necrotic cells. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the complement classical pathway and whether this is regulated by factor H. We show here that both C1q and factor H bind to the fibrin formed in microtiter plates and the fibrin clots formed under in vitro physiological conditions. Both C1q and factor H become covalently bound to fibrin clots, and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the activation of the classical pathway induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences., Competing Interests: Author Y-HK was employed by the company MediMabBio Inc. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kang, Varghese, Aiyan, Pondman, Kishore and Sim.)

Background/objectives: Collagen is commonly used in diverse forms as a functional component in skincare products. On the other hand, the effects of collagen on human skin are controversial. Dietary collagen hydrolysates from freshwater Pangasius hypophthalmus fish skin ameliorated photo-aged skin of hairless mice. This study conducted a randomized, double-blind, placebo-controlled clinical trial to determine if liquid fish collagen (Collagen-Tripep20™, Tripep20) as a drink strengthens skin health and quality., Subjects/methods: In this clinical trial, 85 subjects aged 35-60 yrs were diagnosed with photo-aged skin. Eighty-five subjects were randomized to receive either Tripep20 (n = 44) or placebo (n = 41). Seventy-eight subjects fully participating for a 12-week period consumed 1,000 mg of Tripep20 (n = 41) or placebo (n = 37) in a 50-mL bottle as a daily drink. The intend-to-treat and per-protocol populations were 85 and 78, respectively. Skin hydration, wrinkles, and elasticity were assessed at 0 (baseline), 6, and 12 weeks during the study period., Results: Skin hydration in the Tripep20 group was significantly higher from 6 weeks ( P < 0.001) than the baseline. After 12 weeks, the Crow's-feet visual score and skin roughness (R a , R q , and R max ) were significantly improved in the Tripep20 group than in the placebo group ( P < 0.05). Consuming liquid collagen Tripep20 greatly enhanced skin elasticity (Gross R2, Net R5, and Biological elasticity R7) in 6 weeks compared to the placebo group. The Tripep20 group showed a significant increase in skin elasticity from the baseline after 6 and 12 weeks ( P < 0.001). Neither abnormal symptoms nor adverse events were encountered during the study period in subjects ingesting Tripep20 or placebo. The changes in parameters related to hematology and clinical chemistry were within the normal ranges., Conclusion: Oral consumption of liquid collagen Tripep20 was safe and well-tolerated. The results of this study show that freshwater fish-derived liquid collagen Tripep20 can be used as a healthy functional food ingredient to improve skin moisturizing, anti-wrinkling, and elasticity in an aging population., Competing Interests: Conflict of Interest: JSL, YCY, JMK, YHK, and YCS were employed by Amicogen Inc. The authors declare that this study was fully supported from Amicogen Inc. The funder had the following involvement in the study: study design., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2024 The Korean Society of Radiology.)

Emission uncertainty in North Korea can act as an obstacle when developing air pollution management plans in the country and neighboring countries when the transboundary transport of air pollutants is considered. This study introduces a novel approach for adjusting and reallocating North Korean CO emissions, aiming to complement the limited observational and emissions data on the country's air pollutants. We utilized ground observations from demilitarized zone (DMZ) and vertical column density (VCD) data from a TROPOspheric Monitoring Instrument (TROPOMI), which were combined with the Community Multi-Scale Air Quality (CMAQ) chemistry transport model simulations. The Clean Air Support System (CAPSS) and Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) emissions inventories served as the basis for our initial simulations. A two-step procedure was proposed to adjust both the emission intensity and the spatial distribution of emissions. First, air quality simulations were conducted to explore model sensitivity to changes in North Korean CO emissions with respect to ground concentrations. DMZ observations then constrained these simulations to estimate corresponding emission intensity. Second, the spatial structure of North Korean CO emission sources was reconstructed with the help of TROPOMI CO VCD distributions. Our two-step hybrid method outperformed individual emissions adjustment and spatial reallocation based solely on surface or satellite observations. Validation using ground observations from the Chinese Dandong site near the China-North Korea border revealed significantly improved model simulations when applying the updated CO emissions. The adjusted CO emissions were 10.9 times higher than those derived from the bottom-up emissions used in this study, highlighting the lack of information on North Korean pollutants and emission sources. This approach offers an efficient and practical solution for identifying potential missing emission sources when there is limited on-site information about air quality on emissions., 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 B.V. All rights reserved.)

Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.

Background/objectives: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice., Materials/methods: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage., Results: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice., Conclusion: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Aims: We explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years., Methods: We retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC)., Results: At baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (β: 0.045, p < 0.001; β: -0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9-2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers., Conclusions: The TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers., 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.)

Background: Hair cycle arrest (HCA) is a chronic alopecic disorder in dogs. Clinical responses vary and are often insufficient. Microneedling (MN) has been used as a successful treatment for HCA in dogs; ideal protocols have not yet been established., Objectives: The objective of the study was to compare the efficacy and safety of three needle lengths for MN in dogs with HCA., Animals: Six unrelated client-owned dogs, including five Pomeranians and one mixed-breed dog, diagnosed with HCA., Materials and Methods: Individual alopecic sites were divided into three sections. For each section, different lengths of needles (1, 2 and 3 mm) were used. Efficacy and safety were evaluated at 1, 3 and 6 months. Treated sections were monitored for 20 months., Results: Three months after treatment with 3 mm needles, all sections showed hair regrowth. There was no hair regrowth in two of six sections treated with 2 mm needles, and four of six sections did not show a response to treatment with 1 mm needles. Two dogs developed transient pruritus. Five of six dogs had recurrent hair loss between 5 and 16 months of follow-up., Conclusion and Clinical Relevance: Microneedling using longer needles stimulated better hair regrowth in dogs with HCA. Alopecia relapsed in most dogs and minor pruritus occurred in some dogs., (© 2023 ESVD and ACVD.)

Background: In South Korea, the leading cause of youth death has been suicide for about 20 years. In this study, we conducted a multi-method psychological autopsy to identify the psychiatric diagnosis, developmental history, personality traits, family history, school life, warning signs of suicide, and risk factors related to suicide for the first time in Korea., Methods: This was a postmortem, retrospective, and descriptive study of 36 adolescents who died by suicide between August 2015 and July 2021 in South Korea. We obtained qualitative and quantitative data from the Korean Psychological Autopsy of Adolescent, conducted by the Suicide and School Mental Health Institute, the official student mental health policy-focused research institute of the Korean Ministry of Education., Results: The adolescents comprised equal percentage of girls and boys. Approximately half of the deaths (55.6%) occurred at home and most (72.2%) involved jumping from a height. Most of the adolescents (97.2%) had one major psychiatric disorder before death, with depressive disorder being the most prevalent (75%). They were at a high risk for internet addiction before death. The most common personality trait was avoidance (28.6%), followed by submissiveness (27.3%). Half of the parents reported that the adolescents were satisfied with their school life and the teachers observed that they had no behavioral problems. One year before death, seven (19.4%) adolescents injured themselves and five (13.9%) had attempted suicide. Most of the deceased (80.6%) had expressed suicide warning signs to their families within one year before death. Adolescents had a long experience of family-related adverse events., Conclusions: Most of the adolescents had mental health disorders and expressed suicidal intentions using verbal and nonverbal signs. However, it was challenging for families to recognize the risk signs because of adolescents' personality traits or a good school life. To prevent adolescent suicide, adolescents, parents, and teachers need to be educated to recognize signs of suicide warning signs and equipped to guide adolescents to appropriate care., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the association between adherence to 24-h movement guidelines and metabolic syndrome (MetS) before and during the COVID-19 pandemic., Study Design: Repeated cross-sectional design., Methods: We selected 10,882 adults (2019: n = 5710; 2020: n = 5172) aged ≥20 years from the Korea National Health and Nutrition Examination Survey. Domain-specific physical activity and sedentary behavior were assessed using a global physical activity questionnaire. We also measured the typical sleep duration (h/day) on weekdays and weekends. MetS was defined as the presence of more than three risk factors., Results: During the COVID-19 pandemic, transportation-related physical activity decreased, while the prevalence of abdominal obesity (+3.3 %) and low HDL-C levels (+3.1 %) increased significantly. An elevated risk of MetS was observed in the lower aerobic (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.04-1.58; P = 0.019) and muscular exercise (OR, 1.31; 95% CI, 1.04-1.66; P = 0.023) groups and in the high sedentary behavior (OR, 1.23; 95% CI, 1.00-1.51; P = 0.049) during the pandemic. Sensitivity analysis stratified by sex showed similar patterns with more pronounced changes in MetS components in males. The models also showed significant associations between aerobic physical activity, strength exercises, and sedentary behavior with MetS in males and females., Conclusions: Although sedentary behavior and sleep time remained unchanged, a significant decrease in transportation-related physical activity was observed during the pandemic. Moreover, our findings revealed that aerobic physical activity, strength exercise, and sedentary time during the pandemic were associated with an increased MetS risk. These results highlight the importance of promoting physical activity, particularly during periods of social restriction, to mitigate the pandemic's negative effects on metabolic health., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

To elucidate the anti-inflammatory properties and constituents of Agrimonia pilosa Ledeb. ( A. pilosa ), a comprehensive investigation was conducted employing activity-guided isolation. The anti-inflammatory effects were evaluated through an in vitro nitric oxide (NO) assay on lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Seven bio-active compounds with anti-inflammatory properties were successfully isolated from the butanol fraction and identified as follows: quercetin-7- O -β-d-rhamnoside ( 1 ), apigenin-7- O -β-d-glucopyranoside ( 2 ), kaempferol-7- O -β-d-glucopyranoside ( 3 ), quercetin ( 4 ), kaempferol ( 5 ), apigenin ( 6 ), and apigenin-7- O -β-d-glucuronide-6″-butylester ( 7 ). All isolated compounds showed strong NO inhibitory activity with IC 50 values ranging from 1.4 to 31 µM. Compound 6 demonstrated the most potent NO inhibition. Compound 7 , a rare flavonoid, was discerned as a novel anti-inflammatory agent, ascertained through its inaugural demonstration of nitric oxide inhibition. Subsequently, a comprehensive structure-activity relationship (SAR) analysis was conducted employing eight flavonoids derived from A. pilosa . The outcomes elucidated that flavones exhibit superior NO inhibitory effects compared to flavonols, and the aglycone form manifests greater potency in NO inhibition than the glycone counterpart. These results highlight A. pilosa as a promising source of effective anti-inflammatory agents and indicate its potential as a health-beneficial dietary supplement and therapeutic material.

We propose a protocol for the generation of NOON states of resonator modes. The physical model is composed of two Kerr-nonlinear resonators and a four-level qudit. Using the off-resonant couplings between the resonators and the qudit, qudit-level-dependent frequency shifts on the two resonators are induced. The frequency shifts allow us to drive different resonators to the N-photon state when the qudit is in different intermediate levels. Consequently, the generation of NOON states with arbitrary photon number N can be completed in only three steps, i.e., driving the qudit to a superposition state of the two intermediate levels, driving one of the resonators to its N-photon state, and driving the qudit back to its ground level. Numerical simulations show that, in the regime of strong Kerr nonlinearity and coupling strengths, the protocol can produce the NOON state with high fidelity in the cases of different photon numbers. In addition, it is possible for the protocol to produce acceptable fidelity in the presence of systematic errors and decoherence factors. Therefore, the protocol may provide some useful perspectives for effective generation of photonic NOON states.

Background/objectives: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis., Materials/methods: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk., Results: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice., Conclusions: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

A novel species of the genus Emticicia, designated BHSR1 T , was isolated from a water sample that was collected from the Nakdong River, Republic of Korea, and its taxonomic affiliation was studied using a polyphasic approach. This bacterium was Gram-stain-negative, non-motile, aerobic, curved, rod-shaped, and oxidase- and catalase-negative. The bacterium grew optimally at 37 °C, pH 7.5 and 0% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain BHSR1 T should be affiliated with the genus Emticicia, with a high similarity to Emticicia fontis KCTC 52248 T (98.10%). Phylogenomic analysis also suggested that the strain represents a novel species in the genus Emticicia. The genomic G + C content was 41.9%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization between strain BHSR1 T and its closely related relatives in the genus Emticicia were in ranges of 71.1-75.8%, 69.4-77.5% and 18.6-19.9%, respectively. The gene cluster within BHSR1 T contained genes encoding enzymes that could be involved in hormone degradation. The major cellular fatty acids (> 10%) were summed feature 3 (comprising C 16:1 ω6c and/or C 16:1 ω7c) and iso-C 15:0 . With regards to the polar lipid profile, phosphatidylethanolamine (PE), two unidentified aminolipids and three unidentified lipids were identified as the major compounds. The major respiratory quinone was menaquinone (MK)-7. Based on its phylogenetic, phenotypic, chemotaxonomic, and genomic features, strain BHSR1 T should be considered a novel species in the genus Emticicia of the family Spirosomaceae, for which the name Emticicia fluvialis sp. nov. is proposed. The type strain was considered BHSR1 T (= KCTC 92622 T  = GDMCC 1.3740 T )., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hepatic stellate cell (HSC) activation is a key event in extracellular matrix accumulation, causing hepatic fibrosis. Therefore, identifying chemicals that inhibit HSC activation is an important therapeutic strategy for hepatic fibrosis. The aim of this study was to investigate the therapeutic effects of paeonol on HSC activation. In LX-2 cells, paeonol inhibited the expression of collagen and decreased the expression of HSC activation markers. In mice with thioacetamide-induced liver fibrosis, paeonol treatment decreased the serum levels of aspartate aminotransferase and alanine transaminase and mRNA expression of α-smooth muscle actin, platelet-derived growth factor-β, and connective-tissue growth factor. Investigation of the underlying molecular mechanism of paeonol showed that paeonol inhibits the SMAD2/3 and STAT3 signaling pathways that are important for HSC activation. On the basis of these results, paeonol should be investigated and developed further for hepatic fibrosis treatment., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01440-9., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© The Korean Society of Food Science and Technology 2023. 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.)

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders., (© 2023. The Author(s).)

The purpose of this study was to automatically classify the three-dimensional (3D) positional relationship between an impacted mandibular third molar (M3) and the inferior alveolar canal (MC) using a distance-aware network in cone-beam CT (CBCT) images. We developed a network consisting of cascaded stages of segmentation and classification for the buccal-lingual relationship between the M3 and the MC. The M3 and the MC were simultaneously segmented using Dense121 U-Net in the segmentation stage, and their buccal-lingual relationship was automatically classified using a 3D distance-aware network with the multichannel inputs of the original CBCT image and the signed distance map (SDM) generated from the segmentation in the classification stage. The Dense121 U-Net achieved the highest average precision of 0.87, 0.96, and 0.94 in the segmentation of the M3, the MC, and both together, respectively. The 3D distance-aware classification network of the Dense121 U-Net with the input of both the CBCT image and the SDM showed the highest performance of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve, each of which had a value of 1.00. The SDM generated from the segmentation mask significantly contributed to increasing the accuracy of the classification network. The proposed distance-aware network demonstrated high accuracy in the automatic classification of the 3D positional relationship between the M3 and the MC by learning anatomical and geometrical information from the CBCT images., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Accurate prediction of the grade of invasive ductal carcinoma (IDC) before treatment is vital for individualized therapy and improving patient outcomes. This study aimed to develop and validate a mammography-based radiomics nomogram that would incorporate the radiomics signature and clinical risk factors in the preoperative prediction of the histological grade of IDC., Methods: The data of 534 patients from our hospital with pathologically confirmed IDC (374 in the training cohort and 160 in the validation cohort) were retrospectively analyzed. A total of 792 radiomics features were extracted from the patients' craniocaudal and mediolateral oblique view images. A radiomics signature was generated using the least absolute shrinkage and selection operator method. Multivariate logistic regression was adopted to establish a radiomics nomogram, the utility of which was evaluated using a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA)., Results: The radiomics signature was found to have a significant correlation with histological grade (P < 0.01), but the efficacy of the model is limited. The radiomics nomogram, which incorporated the radiomics signature and spicule sign into mammography, showed good consistency and discrimination in both the training cohort [area under the curve (AUC) = 0.75] and the validation cohort (AUC = 0.75). The calibration curves and DCA demonstrated the clinical usefulness of the proposed radiomics nomogram model., Conclusions: A radiomics nomogram based on the radiomics signature and spicule sign can be used to predict the histological grade of IDC and assist in clinical decision-making for patients with IDC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vibrio mimicus (V. mimicus) is known to cause severe bacterial diseases with high mortality rates in fish, resulting in significant economic losses in the global aquaculture industry. Therefore, the objective of this study was to develop a safe and effective vaccine for protecting Carassius auratus (C. auratus) against V. mimicus infection. Recombinant Lactobacillus casei (L. casei) strains, Lc-pPG-612-OmpU and Lc-pPG-612-OmpU-CTB (surface-displayed), were constructed using a L. casei strain (ATCC 393) as an antigen delivery carrier and the cholera toxin B subunit (CTB) as an adjuvant. The two recombinant strains of L. casei were administered to C. auratus via oral immunization, and the protective efficacy of the oral vaccines was assessed. The results demonstrated that oral immunization with the two strains significantly increased the levels of nonspecific immune indicators in C. auratus, including alkaline phosphatase (AKP), lysozyme (LYS), acid phosphatase (ACP), complement 3 (C3), complement 4 (C4), lectin, and superoxide dismutase (SOD). Moreover, the experiment groups exhibited significant increases in specific immunoglobulin M (IgM) antibodies against OmpU, as well as the transcription of immune-related genes (ie., IL-1β, TNF-α, IL-10, and TGF-β), when compared to the control groups. Following infection of C. auratus with V. mimicus, the mortality rate of the recombinant L. casei-treated fish was observed to be lower compared to the control group. This finding suggests that recombinant L. casei demonstrates effective protection against V. mimicus infection in C. auratus. Furthermore, the addition of the immune adjuvant CTB was found to induce a more robust adaptive and innate immune response in C. auratus, resulting in reduced mortality after infection with V. mimicus., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: In the past decade, unmanned aerial spraying systems (UASS) have emerged as an effective crop treatment platform option, competing with other ground vehicle treatments. The development of this platform has provided an effective spraying system that can be used on all crop types and in all weather conditions. However, related research has not been able to develop a UASS that can be operated in windy conditions with a low drift percentage., Methods: In this research, spraying was simulated in an indoor flight simulator by considering flight speed, altitude, wind speed, wind direction, rotor rotation, interval, spraying pattern, and nozzle type, which were used as the parameters affecting the output value of the coefficient of variation (CV) of spraying. These parameters were referenced as properties that occur in the field, and using machine learning methods, the CV value was used as a dataset to develop a model that can execute pump opening by controlling the flow rate. There are four machine learning methods used, i.e. random forest regression, gradient boosting, ada boost, and automatic relevance determination regression which are compared with simple linear regression and ridge regression as linear regression., Results: The results revealed that the random forest regression model was the most accurate, with R2 of 0.96 and root mean square error (RMSE) of 0.04%. The developed model was used to simulate spraying with pump opening A, which connects two nozzles in front, and pump opening AB, which connects all four nozzles., Discussion: Using the logic based on CV value and pesticide quantity, the model can execute the pump opening against the environment and UASS operation., 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 © 2023 Hanif, Han, Yu, Han, Baek, Lee, Lee and Kang.)

In this study, we developed a practical approach to augment elemental carbon (EC) emissions to improve the reproducibility of the most recent air quality with photochemical grid modeling in support of source-receptor relationship analysis. We demonstrated the usefulness of this approach with a series of simulations for EC concentrations over Northeast Asia during the 2016 Korea-United States Air Quality study. Considering the difficulty of acquiring EC observational data in foreign countries, our approach takes two steps: (1) augmenting upwind EC emissions based on simulated upwind contributions and observational data at a downwind EC monitor considered as the most representative monitor for upwind influences and (2) adjusting downwind EC emissions based on simulated downwind contributions, including the effects of updated upwind emissions from the first step and observational data at the downwind EC monitors. The emission adjustment approach resulted in EC emissions 2.5 times higher than the original emissions in the modeling domain. The EC concentration in the downwind area was observed to be 1.0 μg m -3 during the study period, while the simulated EC concentration was 0.5 μg m -3 before the emission adjustment. After the adjustment, the normalized mean error of the daily mean EC concentration decreased from 48 % to 22 % at ground monitor locations. We found that the EC simulation results were improved at high altitudes, and the contribution of the upwind areas was greater than that of the downwind areas for EC concentrations downwind with or without emission adjustment. This implies that collaborating with upwind regions is essential to alleviate high EC concentrations in downwind areas. The developed emission adjustment approach can be used for any upwind or downwind area when transboundary air pollution mitigation is needed because it provides better reproducibility of the most recent air quality through modeling with improved emission data., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Cold atmospheric plasma is a novel innovative approach for wound care, and it is currently underrepresented in veterinary medicine., Objectives: To investigate the efficacy and safety of using cold atmospheric microwave plasma (CAMP) as an adjunct therapy for wound healing in dogs and cats., Methods: Wound healing outcomes were retrospectively analyzed using clinical records of client-owned dogs and cats who were first managed through standard wound care alone (pre-CAMP period) and subsequently via CAMP therapy (CAMP period). The degree of wound healing was estimated based on wound size and a modified wound scoring system., Results: Of the 27 acute and chronic wounds included in the analysis, 81.48% showed complete healing after the administration of CAMP as an adjunct therapy to standard care. Most wounds achieved complete healing in < 5 weeks. Compared with the pre-CAMP period, the rate of wound healing significantly increased every week in the CAMP period in terms of in wound size (first week, p < 0.001; second week, p = 0.012; third week, p < 0.001) and wound score (first week, p < 0.001; second week, p < 0.001; third week, p = 0.001). No adverse events were noted except for mild discomfort and transient erythema., Conclusions: CAMP is a well-tolerated therapeutic option with immense potential to support the treatment of wounds of diverse etiology in small animal practice. Further research is warranted to establish specific criteria for CAMP treatment according to wound characteristics., Competing Interests: Cheol-Yong Hwang is a founder and chief clinical officer, and Seung Joon Baek is a founder and chief medical officer at IonMedical. IonMedical was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (© 2023 The Korean Society of Veterinary Science.)

Changes in PM 2.5 concentrations are influenced by interwoven impacts of key drivers (e.g., meteorology, local emissions, and regional emissions). However, it is challenging to quantitatively disentangle their impacts individually at once. Therefore, we introduced a multifaceted approach (i.e., meteorology vs. emissions and self-contribution vs. long-range transport) to analyze the effects of major drivers for long- and short-term PM 2.5 concentration changes based on observation and simulation in the month of January during 2016-2021 in Northeast Asia. For the simulations, we conducted modeling with the WRF-CMAQ system. The observed PM 2.5 concentrations in China and South Korea in January 2021 decreased by 13.7 and 9.8 μg/m 3 , respectively, compared to those in January 2016. Emission change was the dominant factor to reduce PM 2.5 concentrations in China (-115%) and South Korea (-74%) for the 6 years. However, the short-term changes in PM 2.5 concentrations between January of 2020-2021 were mainly driven by meteorological conditions in China (-73%) and South Korea (-68%). At the same time, in South Korea located in downwind area, the impact of long-range transport from upwind area (LTI) decreased by 55% (9.6 μg/m 3 ) over the 6 years whereas the impact of local emissions increased (+2.9 μg/m 3 /year) during 2016-2019 but decreased (-4.5 μg/m 3 /year) during 2019-2021. Additionally, PM 2.5 concentrations in the upwind area showed a positive relationship with LTIs. However, for the days when westerly winds became weak in the downwind area, high PM 2.5 concentrations in upwind area did not lead to high LTIs. These results imply that the decline of PM 2.5 concentrations in South Korea was significantly affected by a combination of emission reduction in upwind area and meteorological conditions that hinder long-range transport. The proposed multifaceted approach can identify the main drivers of PM 2.5 concentration change in a region by considering the regional characteristics., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/purpose: The efficacy of neoadjuvant treatment (NAT) for resectable pancreatic cancer remains debatable, particularly in patients with portal vein (PV)/superior mesenteric vein (SMV) contact and elevated serum carbohydrate antigen (CA) 19-9. This study investigated the clinical significance of PV/SMV contact and CA19-9 levels, and the role of NAT in resectable pancreatic cancer., Methods: A total of 775 patients who underwent surgery for resectable pancreatic cancer between 2007 and 2018 were included. Propensity score-matched (PSM) analysis (1:3) was performed based on tumor size, lymph node enlargement, and PV/SMV contact. Subgroup analyses were performed according to PV/SMV contact and CA19-9 level., Results: Among the patients, 52 underwent NAT and 723 underwent upfront surgery. After PSM, NAT group showed better survival than upfront surgery group (median 30.0 vs 22.0 months, P = .047). In patients with PV/SMV contact, NAT tended to have better survival (30.0 vs 22.0 months, P = .069). CA19-9 >150 U/mL was a poor prognostic factor, with NAT showing a significant survival difference compared with upfront surgery (34.0 vs 18.0 months, P = .004)., Conclusions: Neoadjuvant treatment showed better survival than upfront surgery in resectable pancreatic cancer. In patients with PV/SMV contact or CA19-9 >150 U/mL, NAT showed a survival difference compared to upfront surgery; therefore, NAT could be considered in these patients., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

The genus Paenibacillus contains a variety of biologically active compounds that have potential applications in a range of fields, including medicine, agriculture, and livestock, playing an important role in the health and economy of society. Our study focused on the bacterium SS4 T (KCTC 43402 T = GDMCC 1.3498 T ), which was characterized using a polyphasic taxonomic approach. This strain was analyzed using antiSMASH, BAGEL4, and PRISM to predict the secondary metabolites. Lassopeptide clusters were found using all three analysis methods, with the possibility of secretion. Additionally, PRISM found three biosynthetic gene clusters (BGC) and predicted the structure of the product. Genome analysis indicated that glucoamylase is present in SS4 T . 16S rRNA sequence analysis showed that strain SS4 T most closely resembled Paenibacillus marchantiophytorum DSM 29850 T (98.22%), Paenibacillus nebraskensis JJ-59 T (98.19%), and Paenibacillus aceris KCTC 13870 T (98.08%). Analysis of the 16S rRNA gene sequences and Type Strain Genome Server (TYGS) analysis revealed that SS4 T belongs to the genus Paenibacillus based on the results of the phylogenetic analysis. As a result of the matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) results, SS4 T was determined to belong to the genus Paenibacillus . Comparing P. marchantiophytorum DSM 29850 T with average nucleotide identity (ANI 78.97%) and digital DNA-DNA hybridization (dDDH 23%) revealed values that were all less than the threshold for bacterial species differentiation. The results of this study suggest that strain SS4 T can be classified as a Paenibacillus andongensis species and is a novel member of the genus Paenibacillus .

A Gram-strain-negative, strictly aerobic, rod-shaped, catalase-positive, oxidase-positive and pinkish beige colony-forming bacterial strain designated as BMJM1 T was isolated from a marine sample collected from coastal water near Tongyeong, Republic of Korea. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that BMJM1 T represents a member of the genus Leisingera as it is closely related to Leisingera daeponensis KCTC 12794 T (98.27%), Leisingera caerulea DSM 24564 T (97.98%), Leisingera aquaemixtae KCTC 32538 T (97.91%), Leisingera methylohalidivorans DSM 14336 T (97.26%) and Leisingera aquimarina DSM 24565 T (97.25%). Optimal growth occurred at 25-30°C, pH 7.0 and with 2% NaCl. Digital DNA-DNA hybridisation (dDDH) and average nucleotide identity (ANI) values between strain BMJM1 T and the closely related species of the genus Leisingera were below 40 and 90%, respectively, which are far below the thresholds to delineate a novel species. The predominant fatty acids (>10%) are summed feature 8 (C 18:1 ω7 c and/or C 18:1 ω6 c ) (68.4%) and C 14:1 iso E (11.6%). The major polar lipids were phosphatidylethanolamine and phospholipid. The major isoprenoid quinone was ubiquinone-10. The DNA G+C content was 64.0%. On the basis of the results of the polyphasic taxonomic characterisation, BMJM1 T represents a novel species of the genus Leisingera , for which the name is Leisingera thetidis sp. nov. is proposed, with that type strain BMJM1 T (= KCTC 92110 T = GDMCC 1.2992 T ).

Background/objectives: Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization., Materials/methods: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks., Results: Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysin-treated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice., Conclusion: Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosis-associated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)