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Although the primary pandemic of SARS-CoV-2 is over, there are concerns about the resurgence of the next wave of related viruses, including a wide range of variant viruses. The soluble ACE2 (sACE2) inhibits the SARS-CoV-2 spike protein ACE2 interaction and has potential as a variant-independent therapeutic against SARS-CoV-2. Here, we introduce novel disulfide bonds in the wild-type sACE2-Fc by structure-guided mutagenesis, aiming to improve its stability. The stability of each mutant was assessed by a thermal shift assay to screen mutants with increased thermal stability. As a result, we identified a mutant sACE2-Fc with a significantly increased melting temperature. X-ray crystal structure determination of the sACE2 mutant confirmed the correct formation of the designed disulfide bond, and there were no significant structural disturbances. We also proved that the thermostable sACE2-Fc preserved the spike protein binding affinity comparable to the wild-type sACE2-Fc in both molecular and cellular environments, suggesting its therapeutic potential. [ABSTRACT FROM AUTHOR]

With rising global obesity rates, the demand for effective dietary strategies for obesity management has intensified. This study evaluated the potential of kimchi with various probiotics and bioactive compounds as a dietary intervention for high-fat diet (HFD)-induced obesity in rats. Through a comprehensive analysis incorporating global and targeted metabolomics, gut microbiota profiling, and biochemical markers, we investigated the effects of the 12-week kimchi intake on HFD-induced obesity. Kimchi intake modestly mitigated HFD-induced weight gain and remarkably altered gut microbiota composition, steroid hormones, bile acids, and metabolic profiles, but did not reduce adipose tissue accumulation. It also caused significant shifts in metabolomic pathways, including steroid hormone metabolism, and we found substantial interactions between dietary interventions and gut microbiota composition. Although more research is required to fully understand the anti-obesity effects of kimchi, our findings support the beneficial role of kimchi in managing obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Taurolidine, known for its broad-spectrum antimicrobial properties and low toxicity, has shown promise in reducing infections in various surgical settings. However, it has not been extensively evaluated in orthopedic surgery. This study assessed the efficacy of taurolidine irrigation in reducing surgical site infections in patients undergoing ankle fracture surgery. A retrospective review was conducted for patients >20 years old who underwent ankle fracture surgery between March 2016 and March 2023, with follow-ups exceeding 6 months. Patients were classified into the following two groups: those who underwent normal saline (NS) irrigation and those who underwent taurolidine irrigation. Minor infections were defined as requiring additional oral antibiotics postoperatively, while major infections were characterized by hospitalization or reoperation due to infection within 3 months. Of 844 patients, 688 were included. The taurolidine group (n = 328) had a significant reduction in minor infections (7.3% vs. 22.5%, odds ratio = 0.410, p = 0.028) compared to the NS group (n = 360). Major infections were fewer in the NS group (1.2% vs. 0%, p = 0.051), but the number of cases was too small for reliable analysis. Taurolidine irrigation significantly reduces the occurrence of minor infections in ankle fracture surgeries when compared to normal saline irrigation. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to develop an embolic agent with short-term embolic effects using cilastatin as the basic material. Materials and Methods: The particle size distribution of 25 mg cilastatin-based short-term embolic agents was evaluated microscopically under three different mixing conditions. A total of thirty-six healthy male Sprague Dawley rats were divided into four groups. Each group of six rats was injected once into the tail artery with 0.4 mL each of (A) Cilastatin + D-Mannitol Mixture, (B) Iohexol, (C) Prepenem, and (D) embolization promoter (EGgel). Results: A visual inspection of the tail appearance of rats in each group was performed at 0, 3, 7, 15, and 21 days. At weeks 1 and 3, three rats per group were euthanized, and histopathological analyses were performed on the specimens obtained from each group. No significant differences were observed on day 7, but mild inflammation was observed in Group (D) on day 15. Histopathological inflammation scoring of tail central artery embolization was performed using a six-point scale (from 0 = absent to 5 = marked inflammation). Three groups were formed consisting of six male New Zealand white rabbits each: control, positive control, and test groups. The control group received an Iohexol injection (rabbits: 0.8 mL). The positive control and experimental groups were injected with prepenem and cilastatin/D-mannitol compound, respectively (0.8 mL), and vascular angiography was performed. The order of occlusion progression after embolization was as follows: test group, positive control group, and control group. Conclusions: We developed a cilastatin/D-mannitol compound that exhibits characteristics of short-term embolization by utilizing the pharmacokinetic properties of cilastatin and the crystalline material D-mannitol. We evaluated its particle size distribution microscopically, conducted histopathological evaluation including inflammation via animal experiments, and assessed the embolization effect. [ABSTRACT FROM AUTHOR]

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction. [ABSTRACT FROM AUTHOR]

Background: Femoral fractures often lead to complications such as altered pulmonary hemodynamics. Right ventricular global longitudinal strain (RV GLS), which correlates with pulmonary hemodynamics, indicates the subclinical function of the right ventricle (RV). This study aimed to investigate the predictive value of RV GLS for the risk of adverse clinical composite outcomes in patients with femoral fractures. Methods: Data were obtained from a prospective single-center cohort of patients hospitalized for femoral fractures and followed up for at least 1 year between March 2021 and October 2022. The primary outcome was the development of an adverse composite clinical event, which included pneumonia, pulmonary oedema or effusion, pulmonary thromboembolism, and all-cause mortality within the 1-year period following surgery. Results: Among the 163 patients, 36 (22.09%) experienced adverse composite clinical events during 1-year follow-up. The adverse outcome group demonstrated poorer RV GLS and RV free wall strain values than the non-adverse outcome group. The optimal cut-off value of RV GLS for predicting composite adverse clinical events was −12.55%. The cumulative composite event-free survival rate was significantly lower in the RV GLS ≥ −12.55% group (log-rank p-value = 0.003). After adjusting for confounding factors, multivariate Cox proportional hazards regression analyses showed that RV GLS ≥ −12.55% independently increased the risk of composite adverse clinical events by 2.65-fold. Conclusions: Poor RV GLS is a significant predictor of adverse clinical outcomes in patients with femoral fractures. Specifically, an RV GLS value of ≥ −12.55% indicated a substantially increased risk of adverse events. [ABSTRACT FROM AUTHOR]

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration. [ABSTRACT FROM AUTHOR]

This study was conducted to compare and analyze whether Pilates exercise and yoga exercise help improve the performance of female fencers and prevent injury, and the dynamic balance test (LQ-YBT) and functional movement screening (FMS) test score of the elite adult female fencers were compared and analyzed as evaluation indicators. Participants were randomly classified into Pilates (n = 10) and yoga groups (n = 10), members of which took part in 50 min of exercise (5 min of warm-up, 40 min of main exercise, and 5 min of cool-down) twice weekly for eight weeks. The results obtained from this study were analyzed via independent t-test and 2-way ANOVA. The results were as follows: LQ-YBT measures (reaching distance) increased significantly for both groups, as did FMS scores (deep squat, hurdle step, inline lunge, shoulder mobility, active straight-leg raise, trunk-stability push-up, and rotary stability). These results suggest that Pilates exercise and yoga exercise might be likely effective in improving the performance of adult female fencers and injury prevention by increasing their dynamic balance ability and functional movement. [ABSTRACT FROM AUTHOR]

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut–brain interaction. [ABSTRACT FROM AUTHOR]

Recently, a paste-type premixed calcium silicate-based mineral trioxide aggregate (MTA) product that quickly solidifies through a pozzolanic reaction was introduced to replace existing MTA, which has the disadvantage of a long setting time. In this study, we evaluated the effect of moisture content in the root canal on the setting time of premixed calcium silicate-based MTA in a simulated root canal environment using Endoseal MTA and Well-Root ST, among commercially available products. The setting time was measured according to ISO 6876/2012. A mold made using grades 2, 3, and 4 dental gypsum according to the classification of ISO 6873/2013 was used to reproduce the difference in moisture environment. Differences in moisture content were measured using micro-computed X-ray tomography (micro-CT). The micro-CT results showed that the moisture content was the highest and lowest in the grade 2 and 4 gypsum molds, respectively. Moreover, the setting time indicated by the manufacturer was the shortest for the grade 2 gypsum mold. Hence, the differences in moisture content significantly affect the setting time of MTA. This result can help set future experimental conditions and develop premixed calcium silicate-based MTA products. [ABSTRACT FROM AUTHOR]

Citrus fruits have a distinctive flavor and can convey health benefits because of their unique phytochemicals. Phytochemical profiles are influenced by many factors, including variety and environmental growing conditions; however, the effect of the cultivation methods on the phytochemical profile of Satsuma mandarin (Citrus unshiu) has received little attention. In this study, we examined the relationships between the cultivation conditions, sensory quality, and phytochemical profiles of C. unshiu cultivated using four methods: open field, greenhouse, film mulching, and tunnel farming. The soil water content differed significantly between the cultivation methods and showed a strong positive correlation with sourness, bitterness, and astringency and a strong negative correlation with sweetness. The metabolites of C. unshiu were not associated with the soil water content but with the soil mineral content, including nitrogen (N+), phosphorus (P+), and potassium (K+). The soil P+ and K+ content was positively correlated with most secondary metabolites. The relative abundance of sugars did not differ significantly between the cultivation methods; however, the sweetness was higher under film mulching than under the other cultivation methods because of the suppression of sweetness by bitter compounds. We did not investigate the effect of other growing conditions, such as sunlight; however, the results improve our understanding of the effect of cultivation methods on the quality of C. unshiu and may inform crucial decisions concerning citrus cultivation. [ABSTRACT FROM AUTHOR]

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial to mitigating oxidative stress in hostile environments. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella (B.) abortus. In this study, to determine whether the suppression of catalase can inhibit the intracellular growth of B. abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Moreover, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates the cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced the B. abortus proliferation within the spleens and livers of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by the lowered levels of TNF-α, IL-6, and IL-10 and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F−, Cl−, NO3−, SO42−; five cations: Na+, NH4+, K+, Mg2+, Ca2+) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl− concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca2+ and Mg2+), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria. [ABSTRACT FROM AUTHOR]

Developing energy literacy and pathways for youth to clean energy careers are vital for sustainable development, aligning with various Sustainable Development Goals (SDGs), from climate action to quality education. Despite the increasing focus on nurturing energy-literate youth, there is a lack of comprehensive insights into how students develop their energy literacy within diverse learning environments. This study addresses the research question of what factors across various learning environments play a significant role in the development of energy literacy among youth. To address the research question, we develop a conceptual framework for understanding the development of energy literacy among high school students based on a learning ecology perspective. Focusing on students' energy literacy, encompassing information search, attitudes, behaviors, and knowledge of energy, we examined the influence of school-based clean energy program participation, virtual information sources, and interactions with peers and family. Furthermore, we conducted an empirical analysis to identify factors associated with energy literacy among high school students from Alabama high schools. The student sample was intentionally recruited from case study high schools in Alabama that implemented a clean energy education pilot project. This sample includes both program participants and non-participants who completed pre- and post-program surveys, resulting in a total of 189 survey responses. Findings indicate a positive association between the school-based clean energy program and a significantly higher increase in energy-related information searches among program participants compared with non-participants. The virtual learning setting, especially video platforms, was also significantly associated with students' energy-related information searches and positive attitudes toward energy. Findings also indicate that family relationships and pre-existing STEM interests significantly determine youth energy literacy. These findings provide valuable insights for the development and expansion of future energy education programs. If the energy education program incorporates these crucial learning factors and establishes an interconnected learning environment, the convergence of multiple learning aspects within the program can foster a synergistic learning ecosystem for youth energy literacy. [ABSTRACT FROM AUTHOR]

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. We encountered two cases of severe complications due to an esophageal fish bone foreign body. The first case was a 40-year-old male with an intramural esophageal abscess due to a fish bone after eating fish five days before visiting the hospital. The patient underwent surgical treatment, but the esophageal abscess did not improve; so, the abscess was drained through endoscopic mucosal dissection, and the abscess improved. In the second case, a 64-year-old male, who had eaten fish three days before visiting the hospital, had esophageal perforation by a fish bone, and abscess formation in the mediastinum and the lesser sac in the abdominal cavity were observed. Although surgical treatment was performed, the intra-abdominal abscess formation was not controlled; so, percutaneous drainage (PCD) was inserted, and the abscess improved. Both patients were discharged without any complications. Here, we report two cases that were improved through surgical treatments and additional treatments such as endoscopic dissection and PCD. [ABSTRACT FROM AUTHOR]

This study investigated the ameliorating effect of the aqueous extract of Codium fragile on PM2.5-induced pulmonary dysfunction. The major compounds of Codium fragile were identified as palmitic acid, stearic acid, and oleamide using GC/MS2 and hexadecanamide, oleamide, and 13-docosenamide using UPLC-Q-TOF/MSE. Codium fragile improved pulmonary antioxidant system deficit by regulating SOD activities and reducing GSH levels and MDA contents. It suppressed pulmonary mitochondrial dysfunction by regulating ROS contents and mitochondrial membrane potential levels. It regulated the inflammatory protein levels of TLR4, MyD88, p-JNK, p-NF-κB, iNOS, Caspase-1, TNF-α, and IL-1β. In addition, it improved the apoptotic protein expression of BCl-2, BAX, and Caspase-3 and attenuated the fibrous protein expression of TGF-β1, p-Smad-2, p-Smad-3, MMP-1, and MMP-2. In conclusion, this study suggests that Codium fragile might be a potential material for functional food or pharmaceuticals to improve lung damage by regulating oxidative stress inflammation, cytotoxicity, and fibrosis via the TLR/TGF-β1 signaling pathway. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the cognitive dysfunction improvement effect of aqueous extract of Codium fragile (AECF) by regulating the imbalance of the gut–brain axis in chronic particulate matter (PM)2.5-exposed mice. The physiological compounds of AECF were identified as hexadecanamide, oleamide, octadecanamide, stearidonic acid, and linolenic acid by the ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC Q-TOF MSE) analysis. To evaluate the effect of PM2.5 on the antioxidant system, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, and malondialdehyde (MDA) contents were measured in colon and brain tissues. AECF significantly ameliorated the imbalance of the antioxidant systems. Also, AECF improved intestinal myeloperoxidase (MPO) activity, the abundance of the gut microbiome, short-chain fatty acids (SCFAs) contents, and tight junction protein expression against PM2.5-induced damage. In addition, AECF prevented PM2.5-induced inflammatory and apoptotic expression via the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88) pathway in colon and brain tissues. Additionally, AECF enhanced the mitochondrial function, including the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) contents in brain tissues. Furthermore, AECF regulated the cholinergic system, such as acetylcholine (ACh) contents, acetylcholinesterase (AChE) activity, and protein expression levels of AChE and choline acetyltransferase (ChAT) in brain tissues. To evaluate the effect of cognitive dysfunction caused by PM2.5-induced intestinal dysfunction, behavior tests such as Y-maze, passive avoidance, and Morris water maze tests were performed. From the results of the behavior tests, AECF ameliorated spatial learning and memory, short-term memory, and long-term learning and memory function. This study confirmed that AECF reduced PM2.5-induced cognitive dysfunction by regulating gut microbiome and inflammation, apoptosis, and mitochondrial function by enhancing the gut–brain axis. Based on these results, this study suggests that AECF, which contains fatty acid amides, might be a potential material for ameliorating PM2.5-induced cognitive dysfunction via gut–brain axis improvement. [ABSTRACT FROM AUTHOR]

Although numerous citrus varieties have recently been developed to enhance their quality, information on their quality characteristics is limited. We assessed the quality characteristics of Yellowball, a novel citrus variety, by evaluating its appearance, storability, sensory properties, functionality, and metabolite profiles and then comparing these characteristics with those of its parent varieties, Haruka and Kiyomi. The metabolite profiles between the citrus varieties differed significantly, resulting in distinct physicochemical and functional qualities. The storability of Yellowball was significantly increased compared with that of its parent varieties owing to its strong antifungal activity and unique peel morphology, including the stoma and albedo layers. While we did not investigate the volatile compounds, overall functional activities, and detailed characteristics of each metabolite, our data provide valuable insights into the relationship between citrus metabolites, peel morphology, physicochemical properties, and storability, and demonstrate the potential of Yellowball as a promising variety in the citrus industry. [ABSTRACT FROM AUTHOR]

Background/Aims: The incidence of pancreatic cancer (PC) is gradually increasing among elderly individuals, but there are insufficient clinical data on elderly individuals. To determine the efficacy and safety of chemotherapy, we compared the. the outcomes of elderly patients with unresectable PC. Methods: We enrolled patients aged 75 years or older diagnosed with PC from 1 January 2010 to 30 November 2021. Propensity score matching (PSM) was used to reduce the heterogeneity of the study population. For efficacy evaluation, the median overall survival (OS) was estimated for the chemotherapy and nonchemotherapy groups. Chemotherapy tolerability evaluations were also investigated. Results: The study included 115 patients, 47 of whom received chemotherapy and 68 who did not. After PSM, compared with the nonchemotherapy group, the chemotherapy group had more myocardial infarctions (14.6 vs. 0.0%, p < 0.001) and chronic obstructive pulmonary disease (4.4 vs. 0.0%, p = 0.043). The primary endpoint, median OS, was significantly different in the with vs. without chemotherapy groups (203 vs. 106 days, p = 0.013). In the chemotherapy group, 10 patients (21.3%) discontinued treatment due to adverse events. However, there were no reports of death due to severe adverse events. Conclusions: This study demonstrated that chemotherapy improved median OS among elderly patients. These data could support the use of chemotherapy for elderly patients with unresectable PC. [ABSTRACT FROM AUTHOR]

This study aimed to assess the protective effect of an extract of Lonicera japonica against particulate-matter (PM)2.5-induced pulmonary inflammation and fibrosis. The compounds with physiological activity were identified as shanzhiside, secologanoside, loganic acid, chlorogenic acid, secologanic acid, secoxyloganin, quercetin pentoside, and dicaffeoyl quinic acids (DCQA), including 3,4-DCQA, 3,5-DCQA, 4,5-DCQA, and 1,4-DCQA using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The extract of Lonicera japonica reduced cell death, reactive oxygen species (ROS) production, and inflammation in A549 cells. The extract of Lonicera japonica decreased serum T cells, including CD4+ T cells, CD8+ T cells, and total T helper 2 (Th2) cells, and immunoglobulins, including immunoglobulin G (IgG) and immunoglobulin E (IgE), in PM2.5-induced BALB/c mice. The extract of Lonicera japonica protected the pulmonary antioxidant system by regulating superoxide dismutase (SOD) activity, reduced glutathione (GSH) contents, and malondialdehyde (MDA) levels. In addition, it ameliorated mitochondrial function by regulating the production of ROS, mitochondrial membrane potential (MMP), and ATP contents. Moreover, the extract of Lonicera japonica exhibited a protective activity of apoptosis, fibrosis, and matrix metalloproteinases (MMPs) via TGF-β and NF-κB signaling pathways in lung tissues. This study suggests that the extract of Lonicera japonica might be a potential material to improve PM2.5-induced pulmonary inflammation, apoptosis, and fibrosis. [ABSTRACT FROM AUTHOR]

This study was conducted to compare the synbiotic activity between Corni fructus (C. fructus) and Limosilactobacillus reuteri (L. reuteri) on dextran sulfate sodium (DSS)-induced colitis and cognitive dysfunction in C57BL/6 mice. C. fructus (as prebiotics, PRE), L. reuteri (as probiotics, PRO), and synbiotics (as a mixture of L. reuteri and C. fructus, SYN) were fed to mice for 3 weeks. Consumption of PRE, PRO, and SYN ameliorated colitis symptoms in body weight, large intestinal length, and serum albumin level. Moreover, SYN showed a synergistic effect on intestinal permeability and intestinal anti-inflammation response. Also, SYN significantly improved cognitive function as a result of measuring the Y-maze and passive avoidance tests in DSS-induced behavioral disorder mice. Especially, SYN also restored memory function by increasing the cholinergic system and reducing tau and amyloid β pathology. In addition, PRE, PRO, and SYN ameliorated dysbiosis by regulating the gut microbiota and the concentration of short-chain fatty acids (SCFAs) in feces. The bioactive compounds of C. fructus were identified with quinic acid, morroniside, loganin, and cornuside, using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS2). In conclusion, synbiotic supplementation alleviated DSS-induced colitis and cognitive dysfunction by modulating gut microbiota, proinflammatory cytokines, and SCFAs production. [ABSTRACT FROM AUTHOR]

SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation. [ABSTRACT FROM AUTHOR]

Aspergillus oryzae (A. oryzae) is an important starter in the fermentation of koji and moromi. However, the effect of different A. oryzae strains on the quality of moromi has rarely been studied. For this reason, this study analyzed the physicochemical properties, enzyme activity, sensory quality, and metabolite profiles of moromi samples fermented using two strains (A. oryzae KCCM12012P (moromi-1) and KCCM12804P (moromi-2)), which were newly isolated from fermented soy foods, and compared them to those of a commercialized A. oryzae strain (control). Amino-type nitrogen contents of moromi-1 and moromi-2 samples were higher than that of control moromi, and their amylase and protease activities were also higher. Moreover, metabolite profiles of moromi were significantly altered according to strains. In particular, the levels of many amino acids, peptides, nucleotides, and acidic compounds were altered, which resulted in changes in the sensory quality of moromi. Although volatile compounds were not investigated, the results suggested that the quality of moromi was significantly different for newly isolated strains, especially A. oryzae KCCM12804P, and they were superior to the commercial strain in terms of taste-related substances. Therefore, these strains could be used as good starters to produce moromi and soy sauce with good sensory quality. [ABSTRACT FROM AUTHOR]

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected medical practice in diverse ways. We aimed to investigate the change in trends of lower gastrointestinal (LGI) endoscopy conducted in children and adolescents after the COVID-19 outbreak in Korea. Material and Methods: This was a multicenter, retrospective study conducted in Korea. We included children and adolescents aged <19 years who had undergone their first LGI endoscopy between 2016 and 2020. We compared clinicodemographic and endoscopic factors between groups divided according to the pre- and postCOVID-19 era in Korea. Results: We included 1307 patients in this study. Colonoscopies, instead of sigmoidoscopies, were conducted in most patients in the postCOVID-19 era compared to those in the preCOVID-19 era (86.9% vs. 78.5%, p = 0.007). The diagnosis of inflammatory bowel disease (IBD) was also significantly higher in the postCOVID-19 era compared to the preCOVID-19 era (47.2% vs. 28.5%, p < 0.001). According to multivariate logistic regression analysis, age at LGI endoscopy, LGI bleeding indication, and IBD diagnosis were independently associated with the use of a colonoscopy over a sigmoidoscopy (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.12–1.27, p < 0.001; OR 0.56, 95% CI 0.37–0.83, p = 0.005; OR 1.80, 95% CI 1.20–2.77, p = 0.006, respectively). Conclusions: The COVID-19 pandemic has changed LGI endoscopy practice trends of pediatric gastroenterologists in Korea, who tended to perform lesser LGI endoscopies compared to previous years while conducting significantly more colonoscopies than sigmoidoscopies in the postCOVID-19 era. Furthermore, these colonoscopies were significantly associated with the diagnosis of IBD, as well as a significant increase in IBD diagnosis in the postCOVID-19 era. [ABSTRACT FROM AUTHOR]

Hemp (Cannabis sativa L.) is used for medicinal purposes owing to its anti-inflammatory and antioxidant activities. We evaluated the protective effect of nanovesicles isolated from hemp plant parts (root, seed, hemp sprout, and leaf) in dextran sulfate sodium (DSS)-induced colitis in mice. The particle sizes of root-derived nanovesicles (RNVs), seed-derived nanovesicles (SNVs), hemp sprout-derived nanovesicles (HSNVs), and leaf-derived nanovesicles (LNVs) were within the range of 100–200 nm as measured by nanoparticle tracking analysis. Acute colitis was induced in C57BL/N mice by 5% DSS in water provided for 7 days. RNVs were administered orally once a day, leading to the recovery of both the small intestine and colon lengths. RNVs, SNVs, and HSNVs restored the tight (ZO-1, claudin-4, occludin) and adherent junctions (E-cadherin and α-tubulin) in DSS-induced small intestine and colon injury. Additionally, RNVs markedly reduced NF-κB activation and oxidative stress proteins in DSS-induced small intestine and colon injury. Tight junction protein expression and epithelial cell permeability were elevated in RNV-, SNV-, and HSNV-treated T84 colon cells exposed to 2% DSS. Interestedly, RNVs, SNVs, HSNVs, and LNVs reduced ALT activity and liver regeneration marker proteins in DSS-induced liver injury. These results showed for the first time that hemp-derived nanovesicles (HNVs) exhibited a protective effect on DSS-induced gut leaky and liver injury through the gut–liver axis by inhibiting oxidative stress marker proteins. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) is the major factor in the development of chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Furthermore, although Camellia sinensis (CN) has been known as an anti-inflammatory material, the effect of CN has not yet been known on pulmonary inflammation in COPD. Thus, we investigated the protective effects of Camellia sinensis L. extract (CLE) against pulmonary inflammation in porcine pancreas elastase (PPE) and a cigarette smoke extract (CSE)-induced COPD mouse model. Oral administration of CLE suppressed the symptoms such as infiltration of immune cells, cytokines/chemokines secretion, mucus hypersecretion, and injuries of the lung parenchyma. Increased inflammatory responses in COPD are mediated by various immune cells such as airway epithelial cells, neutrophils, and alveolar macrophages. Thus, we investigated the effect and mechanisms of CLE in H292, HL-60, and MH-S cells. The CLE inhibited the expression of IL-6, IL-8, MUC5AC and MUC5B on CSE/LPS-stimulated H292 cells and also suppressed the formation of neutrophil extracellular traps and secretion of neutrophil elastase by inhibiting reactive oxygen species in PMA-induced HL-60 cells. In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2′,7′-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments. [ABSTRACT FROM AUTHOR]

Sulfur is an essential nutrient required for plant growth and metabolism, and plays an important role in relieving stress. Nutrient deficiency is one of the main factors that negatively affect crop growth, quality, and yield. This study aimed to evaluate the effect of sulfur nutrients on the growth and metabolites of lettuce after treatment with two different sulfur concentrations (16 μM and 2 mM) in spray hydroponics. The fresh weight, chlorophyll, and carotenoid content of lettuce leaves were analyzed. Root morphology was examined using the WinRHIZO program. Metabolites were comparatively evaluated with the help of LC-MS and GC-MS. The fresh weight, chlorophyll, and carotenoid contents of lettuce were higher in the high concentration sulfur treatment group than in the low concentration sulfur treatment group. In the characteristics analysis of the lettuce roots, treatment with a high concentration of sulfur had a more positive effect on the lettuce root development than treatment with a low concentration of sulfur. Moreover, mass-based metabolomics analysis showed that the lettuce metabolites content was significantly different according to low- and high-concentration sulfur treatments. Therefore, this study highlights the importance of sulfur nutrient content in lettuce growth and metabolites. [ABSTRACT FROM AUTHOR]

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling. [ABSTRACT FROM AUTHOR]

To evaluate the biological effects of Porphyra tenera (P. tenera), we tried to confirm the possibility that the intake of P. tenera could modulate cognitive and intestinal functions in PM2.5-induced cognitive decline mice. P. tenera attenuated PM2.5-induced learning and memory impairment through antioxidant and anti-inflammatory effects by regulating the mitochondrial function and TLR-initiated NF-κB signaling. In addition, P. tenera effectively alleviated Aβ production/tau phosphorylation by inhibiting the JNK phosphorylation. Also, the bioactive constituents of P. tenera determined the sulfated galactan, mycosporine-like amino acids (MAAs), and chlorophyll derivatives. Moreover, the bioactive compounds of P. tenera by gut fermentation protected against gut dysbiosis and intestinal tight junction damage with a decrease in inflammatory response and short-chain fatty acid production. Based on these results, our findings suggest that P. tenera with sulfated galactan and MAAs is a potential material for cognitive function improvement. [ABSTRACT FROM AUTHOR]

Although vasodilators are widely used in patients with vasospastic angina (VA), few studies have compared the long-term prognostic effects of different types of vasodilators. We investigated the long-term effects of vasodilators on clinical outcomes in VA patients according to the type of vasodilator used. Study data were obtained from a prospective multicenter registry that included patients who had symptoms suggestive of VA. Patients were classified into two groups according to use of nitrates (n = 239) or other vasodilators (n = 809) at discharge. The composite clinical events rate, including acute coronary syndrome (ACS), cardiac death, new-onset arrhythmia (including ventricular tachycardia and ventricular fibrillation), and atrioventricular block, was significantly higher in the nitrates group (5.3% vs. 2.2%, p = 0.026) during one year of follow-up. Specifically, the prevalence of ACS was significantly more frequent in the nitrates group (4.3% vs. 1.5%, p = 0.024). After propensity score matching, the adverse effects of nitrates remained. In addition, the use of nitrates at discharge was independently associated with a 2.69-fold increased risk of ACS in VA patients. In conclusion, using nitrates as a vasodilator at discharge can increase the adverse clinical outcomes in VA patients at one year of follow-up. Clinicians need to be aware of the prognostic value and consider prescribing other vasodilators. [ABSTRACT FROM AUTHOR]

Simple Summary: Intramuscular fat content is one of the important beef quality traits due to its contribution to beef palatability, including flavor, tenderness, and juiciness. Intramuscular fat content is determined by fat synthesis using substrates such as acetate and glucose in ruminants. Beet pulp is a byproduct of sugar beet processing and contains abundant neutral detergent fiber and pectin, with these two components readily fermentable in the rumen. Beet pulp may be a useful energy source in cattle to produce acetate during ruminal fermentation, thereby aiding in lipogenesis (fatty acid synthesis). In this study, partial substitution of corn grain in the diet with beet pulp increased ruminal acetate proportion and circulating insulin levels in beef cattle. Beet pulp could be used as a lipogenic energy source without affecting growth performance in cattle. We investigated the effects of the partial substitution of corn grain in the diet with beet pulp on growth performance, ruminal fermentation characteristics, microbial profiles, and blood lipogenic parameters in fattening steers. Twelve Korean cattle steers (body weight, 485 ± 19.32 kg; age, 18.0 ± 0.17 months) were equally divided into corn grain (CG) and beet pulp (BP) groups. Approximately 75% of dry matter of the requirement was offered as a concentrate portion, and the remaining 25% was offered as oat straw. Eighty percent of the concentrate portion was provided by a pelleted basal concentrate, and the remaining 20% with corn grain for the CG group, or 18% beet pulp plus 2.0% rumen-protected fat for the BP group, respectively, by top dressing. The experiment was conducted for 14 weeks, including a 2-week acclimation period. Growth rate was not affected by beet pulp feeding (p = 0.55). The molar proportions of ruminal acetate (p < 0.05) on wk 4, the relative abundances of ruminal cellulolytic bacteria, including Fibrobacter succinogenes (p = 0.01) and Ruminococcus albus (p = 0.04) on wk 12, and serum insulin concentrations (p < 0.05) on wk 12 were higher in the BP group than in the CG group, whereas the molar proportions of propionate (p < 0.05) on wks 8 and 12 and serum nonesterified fatty acids (p < 0.05) on wk 12 were lower in the BP group. Beet pulp could be used as a lipogenic energy source without affecting growth performance during the fattening period of cattle. [ABSTRACT FROM AUTHOR]

Metabolic diseases (MDs), including cardiovascular diseases (CVDs) and diabetes, occur when the body's normal metabolic processes are disrupted. Behavioral risk factors such as obesity, physical inactivity, and dietary habits are strongly associated with a higher risk of MD. However, scientific evidence strongly suggests that balanced, healthy diets containing non-digestible carbohydrates (NDCs), such as dietary fiber and resistant starch, can reduce the risk of developing MD. In particular, major properties of NDCs, such as water retention, fecal bulking, viscosity, and fermentation in the gut, have been found to be important for reducing the risk of MD by decreasing blood glucose and lipid levels, increasing satiety and insulin sensitivity, and modifying the gut microbiome. Short chain fatty acids produced during the fermentation of NDCs in the gut are mainly responsible for improvement in MD. However, the effects of NDCs are dependent on the type, source, dose, and duration of NDC intake, and some of the mechanisms underlying the efficacy of NDCs on MD remain unclear. In this review, we briefly summarize current studies on the effects of NDCs on MD and discuss potential mechanisms that might contribute to further understanding these effects. [ABSTRACT FROM AUTHOR]

Citrus fruits undergo significant metabolic profile changes during their development process. However, limited information is available on the changes in the metabolites of Citrus unshiu during fruit development. Here, we analyzed the total phenolic content (TPC), total carotenoid content (TCC), antioxidant activity, and metabolite profiles in C. unshiu fruit flesh during different stages of fruit development and evaluated their correlations. The TPC and antioxidant activity significantly decreased during fruit development, whereas the TCC increased. The metabolite profiles, including sugars, acidic compounds, amino acids, flavonoids, limonoids, carotenoids, and volatile compounds (mono- and sesquiterpenes), in C. unshiu fruit flesh also changed significantly, and a citrus metabolomic pathway related to fruit development was proposed. Based on the data, C. unshiu fruit development was classified into three groups: Group 1 (Aug. 1), Group 2 (Aug. 31 and Sep. 14), and Group 3 (Oct. 15 and Nov. 16). Although citrus peel was not analyzed and the sensory and functional qualities during fruit development were not investigated, the results of this study will help in our understanding of the changes in chemical profile during citrus fruit development. This can provide vital information for various applications in the C. unshiu industry. [ABSTRACT FROM AUTHOR]

Background and Objective: There is increasing interest in preventing periodontitis using natural products. The purpose of this study was to investigate the effect of Colocasia antiquorum var. esculenta (CA) varnish on the oral microbiome and alveolar bone loss in a mouse periodontitis model. Materials and Methods: Antibacterial activity against Porphyromonas gingivalis (P. gingivalis) ATCC 53978 and cell cytotoxicity using CCK-8 on L929 cells were measured. Balb/c mice were assigned into five groups (negative control, positive control, CA in drinking water, varnish, and CA varnish). P. gingivalis was administered to the mice by oral gavage three times. After sacrifice, the oral microbiome and the levels of the inflammatory cytokine IL-1β and matrix metalloproteinase-9 were analyzed. Alveolar bone loss was measured using micro-computed tomography. Results: CA extract showed an antibacterial effect against P. gingivalis (p < 0.05) and showed no cytotoxicity at that concentration (p > 0.05). Although alpha diversity of the oral microbiome did not statistically differ between the groups (p > 0.05), the relative abundance of dominant bacteria tended to be different between the groups. The inflammatory cytokine IL-1β was reduced in the CA varnish group (p < 0.05), and no difference was observed in MMP-9 expression and alveolar bone loss (p > 0.05). Conclusions: CA varnish did not affect the overall microflora and exhibited an anti-inflammatory effect, suggesting that it is possibility a suitable candidate for improving periodontitis. [ABSTRACT FROM AUTHOR]

This study proposes the optimization method of the associative knowledge graph using TF-IDF based ranking scores. The proposed method calculates TF-IDF weights in all documents and generates term ranking. Based on the terms with high scores from TF-IDF based ranking, optimized transactions are generated. News data are first collected through crawling and then are converted into a corpus through preprocessing. Unnecessary data are removed through preprocessing including lowercase conversion, removal of punctuation marks and stop words. In the document term matrix, words are extracted and then transactions are generated. In the data cleaning process, the Apriori algorithm is applied to generate association rules and make a knowledge graph. To optimize the generated knowledge graph, the proposed method utilizes TF-IDF based ranking scores to remove terms with low scores and recreate transactions. Based on the result, the association rule algorithm is applied to create an optimized knowledge model. The performance is evaluated in rule generation speed and usefulness of association rules. The association rule generation speed of the proposed method is about 22 seconds faster. And the lift value of the proposed method for usefulness is about 0.43 to 2.51 higher than that of each one of conventional association rule algorithms. [ABSTRACT FROM AUTHOR]

We present the first demonstration of the environmental application of a polyimide film (Kapton) with patterned thru-holes as a novel, efficient, flexible, recyclable, and active particulate matter (PM) air filter. The Kapton air filter captures PM using micro-sized thru-holes and the strong electrostatic force because of its high work function. It is highly efficient, transparent, flexible, and heat-resistant. Furthermore, it can be recycled simply by washing it with tap water. The proposed PM filter is a promising candidate for use as a highly efficient and economical recyclable air filter for home appliances, such as air-purifiers, air-conditioners, and humidifiers, as well as industrial filtration systems. [ABSTRACT FROM AUTHOR]

Salt is one of the most important factors for fermented foods, but the effect of salt treatment time on the quality of fermented foods has rarely been studied. In this study, the effect of different salt treatment times (0, 48, and 96 h) after the start of fermentation on the quality of the soy sauce moromi extract (SSME) was investigated. As the salt treatment time was delayed, the population of Aspergillus oryzae, Lactobacillaceae, and Enterococcaecea in SSME increased, whereas the population of Staphylococcaceae and Bacillaceae decreased, leading to changes in the enzymatic activity and metabolite profiles. In particular, the contents of amino acids, peptides, volatile compounds, acidic compounds, sugars, and secondary metabolites were significantly affected by the salt treatment time, resulting in changes in the sensory quality and appearance of SSME. The correlation data showed that metabolites, bacterial population, and sensory parameters had strong positive or negative correlations with each other. Moreover, based on metabolomics analysis, the salt treatment-time-related SSME metabolomic pathway was proposed. Although further studies are needed to elucidate the salt treatment mechanism in fermented foods, our data can be useful to better understand the effect of salt treatment time on the quality of fermented foods. [ABSTRACT FROM AUTHOR]

Chronic airway exposure to harmful substances, such as deleterious gases, cigarette smoke (CS), and particulate matter, triggers chronic obstructive pulmonary disease (COPD), characterized by impaired lung function and unbridled immune responses. Emerging epigenomic and genomic evidence suggests that excessive recruitment of alveolar macrophages and neutrophils contributes to COPD pathogenesis by producing various inflammatory mediators, such as reactive oxygen species (ROS), neutrophil elastase, interleukin (IL) 6, and IL8. Recent studies showed that Epilobium species attenuated ROS, myeloperoxidase, and inflammatory cytokine production in murine and human innate immune cells. Although the Epilobium genus exerts anti-inflammatory, antioxidant, and antimicrobial effects, the question of whether the Epilobium species regulate lung inflammation and innate immune response in COPD has not been investigated. In this study, Epilobium pyrricholophum extract (EPE) suppressed inflammatory cell recruitment and clinical symptoms in porcine pancreatic elastase and CS extract-induced COPD mice. In addition, EPE attenuated inflammatory gene expression by suppressing MAPKs and NFκB activity. Furthermore, UPLC-Q-TOF MS analyses revealed the anti-inflammatory effects of the identified phytochemical constituents of EPE. Collectively, our studies revealed that EPE represses the innate immune response and inflammatory gene expression in COPD pathogenesis in mice. These findings provide insights into new therapeutic approaches for treating COPD. [ABSTRACT FROM AUTHOR]

Our previous clinical studies demonstrated the synergistic therapeutic effect induced by co-administering recombinant human erythropoietin (rhEPO) in human umbilical cord blood (hUCB) therapy for children with cerebral palsy. However, the cellular mechanism beyond the beneficial effects in this combination therapy still needs to be elucidated. A hypoxic–ischemic encephalopathy (HIE) model of neonates, representing cerebral palsy, was prepared and randomly divided into five groups (hUCB+rhEPO combination, hUCB, and rhEPO treatments over HIE, HIE control, and sham). Seven days after, hUCB was administered intraperitoneally and the rhEPO injections were started. Neurobehavioral tests showed the best outcome in the combination therapy group, while the hUCB and rhEPO alone treatments also showed better outcomes compared with the control (p < 0.05). Inflammatory cytokines were downregulated by the treatments and attenuated most by the combination therapy (p < 0.05). The hUCB+rhEPO treatment also showed remarkable increase in phosphorylation of Akt and potentiation of anti-apoptotic responses with decreased Bax and increased Bcl-2 (p < 0.05). Pre-treatment of MK-2206, an Akt inhibitor, for the combination therapy depressed the anti-apoptotic effects. In conclusion, these findings suggest that the therapeutic effect of hUCB therapy might be potentiated by co-administration of rhEPO via augmentation of anti-inflammatory and anti-apoptotic responses related to the phosphorylation of Akt. [ABSTRACT FROM AUTHOR]

Many citrus varieties are hybridized to improve their quality and to overcome the effects of climate change. However, there is limited information on the effect of the chemical profiles of hybrid varieties on their quality. In this study, we analyzed 10 citrus varieties and evaluated the correlation with their general characteristics and antioxidant activities. Chemical profiles, including the contents of sugars, organic acid compounds, flavonoids, limonoids, and carotenoids, which are related to taste, color, and health benefits, were significantly different depending on the citrus varieties, leading to different antioxidant capacities and general quality parameters. Based on these data, the correlations were investigated, and 10 citrus varieties were clustered into four groups—Changshou kumquat and Jeramon (cluster I); Setoka (cluster II-1); Natsumi, Satsuma mandarin, and Navel orange (cluster II-2); Kanpei, Tamnaneunbong, Saybyeolbong, and Shiranui (cluster II-3). Moreover, a metabolomic pathway was proposed. Although citrus peels were not analyzed and the sensory and functional qualities of the citrus varieties were not investigated in this study, our results are useful to better understand the relationship between citrus quality and metabolite profiles, which can provide basic information for the development and improvement of new citrus varieties. [ABSTRACT FROM AUTHOR]

Pladienolides, an emerging class of naturally occurring spliceosome modulators, exhibit interesting structural features, such as highly substituted 12-membered macrocycles and epoxide-containing diene side chains. The potential of pladienolides as anti-cancer agents is confirmed by H3B-8800, a synthetic analog of this natural product class, which is currently under Phase I clinical trials. Since its isolation in 2004 and the first total synthesis in 2007, a dozen total syntheses and synthetic approaches toward the pladienolide class have been reported to date. This review focuses on the eight completed total syntheses of naturally occurring pladienolides or their synthetic analogs, in addition to a synthetic approach to the main framework of the natural product. [ABSTRACT FROM AUTHOR]

Hypertensive urgency is characterized by an acute increase in blood pressure without acute target organ damage, which is considered to be managed with close outpatient follow-up. However, limited data are available on the prognosis of these cases in emergency departments. We investigated the characteristics and predictors of all-cause mortality in Korean emergency patients with hypertensive urgency. This cross-sectional study included patients aged ≥18 years who visited an emergency tertiary referral center between January 2016 and December 2019 for hypertensive urgency, which was defined as a systolic blood pressure of ≥180 mmHg and a diastolic blood pressure of ≥110 mmHg, or both, without acute target organ damage. The 1 and 3 year all-cause mortality rates were 6.8% and 12.1%, respectively. The incidence of emergency department revisits and readmission after 3 months and 1 year was significantly higher in non-survivors than in survivors. In a multivariate analysis, age ≥ 60 years (hazard ratio (HR), 16.66; 95% CI, 6.20–44.80; p < 0.001), male sex (HR, 1.54; 95% CI, 1.22–1.94; p < 0.001), history of chronic kidney disease (HR, 2.18; 95% CI, 1.53–3.09; p < 0.001), and proteinuria (HR, 1.94; 95% CI, 1.53–2.48; p < 0.001) were independent predictors of 3 year all-cause mortality. The all-cause mortality rate of hypertensive urgency remains high despite the increased utilization of antihypertensive medications. Old age, male sex, history of chronic kidney disease, and proteinuria were poor prognostic factors for all-cause mortality in patients with hypertensive urgency. [ABSTRACT FROM AUTHOR]

Vasospastic angina (VA) is a functional disease of the coronary artery and occurs in an angiographically normal coronary artery. However, it may also occur with coronary artery stenosis. We investigated the effect of coronary artery stenosis on clinical outcomes in VA patients. Study data were obtained from a prospective multicenter registry that included patients who had symptoms of VA. Patients were classified into two groups according to presence of significant coronary artery stenosis. Among 1920 patients with VA, 189 patients were classified in the "significant stenosis" group. The one-year composite clinical events rate was significantly higher in the significant stenosis group than in the "no significant stenosis" group (5.8% vs. 1.4%, respectively; p < 0.001). Additionally, the prevalence of ACS was significantly greater in the "significant stenosis" group (4.8% vs. 0.9%, respectively; p < 0.001). After propensity score matching, the adverse effects of significant stenosis remained. In addition, significant stenosis was independently associated with a 6.67-fold increased risk of ACS in VA patients. In conclusion, significant coronary artery stenosis can increase the adverse clinical outcomes in VA patients at long-term follow-up. Clinicians should manage traditional risk factors associated with atherosclerosis and control vasospasm as well as reduce the burden of atherosclerosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens' metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer. [ABSTRACT FROM AUTHOR]

Infectious bronchitis virus (IBV) was first identified in the 1930s and it imposes a major economic burden on the poultry industry. In particular, GI-19 lineage has spread globally and has evolved constantly since it was first detected in China. In this study, we analyzed S1 gene sequences from 60 IBVs isolated in South Korea. Two IBV lineages, GI-15 and GI-19, were identified in South Korea. Phylogenetic analysis suggested that there were six distinct subgroups (KM91-like, K40/09-like, and QX-like I to IV) of the South Korean GI-19 IBVs. Among them, QX-type III and IV subgroups, which are phylogenetically different from those reported in South Korea in the past, accounted for more than half of the total. Moreover, the phylogeographic analysis of the QX-like subgroups indicated at least four distinct introductions of GI-19 IBVs into South Korea during 2001–2020. The efficacy of commercialized vaccines against the recently introduced QX-like subgroups should be verified, and continuous international surveillance efforts and quarantine procedures should be enhanced to prevent the incursion of viruses. [ABSTRACT FROM AUTHOR]

This study aimed to identify differences in clinical and dietary characteristics, serum adipokine levels, and metabolomic profiles between early- and late-onset gout. Eighty-three men with gout were divided into an early-onset group (n = 38, aged < 40 years) and a late-onset group (n = 45, aged ≥ 40 years). Dietary and clinical information was obtained at baseline. Serum adipokines, including adiponectin, resistin, leptin, and plasminogen activator inhibitor-1 (PAI-1), were quantified by a Luminex multiplex immunoassay. Metabolite expression levels in plasma were measured in 22 representative samples using metabolomics analysis based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Average body mass index, rate of consumption of sugar-sweetened beverages, and serum uric acid levels were significantly higher in the early-onset group (p < 0.05), as was the PAI-I concentration (105.01 ± 42.45 ng/mL vs. 83.76 ± 31.16 ng/mL, p = 0.013). Changes in levels of metabolites mostly involved those related to lipid metabolism. In the early-onset group, acylcarnitine analog and propylparaben levels were downregulated and negatively correlated with the PAI-1 concentration whereas LPC (22:6) and LPC (18:0) levels were upregulated and positively correlated with the PAI-1 concentration. Dietary and clinical features, serum adipokine concentrations, and metabolites differed according to whether the gout is early-onset or late-onset. The mechanisms of gout may differ between these groups and require different treatment approaches. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effect of lipid emulsion (LE) on the vasoconstriction induced by dexmedetomidine (DMT) in the isolated rat aorta and elucidate the associated cellular mechanism. The effect of LE, NW-nitro-L-arginine methyl ester (L-NAME), and methyl-β-cyclodextrin (MβCD) on the DMT-induced contraction was examined. We investigated the effect of LE on the DMT-induced cyclic guanosine monophosphate (cGMP) formation and DMT concentration. The effect of DMT, LE, 4-Amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine,4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), and rauwolscine on the phosphorylation of endothelial nitric oxide synthase (eNOS), caveolin-1, and Src kinase was examined in the human umbilical vein endothelial cells. L-NAME, MβCD, and LE (1%, standardized mean difference (SMD): 2.517) increased the DMT-induced contraction in the endothelium-intact rat aorta. LE (1%) decreased the DMT (10−6 M) concentration (SMD: −6.795) and DMT-induced cGMP formation (SMD: −2.132). LE (1%) reversed the DMT-induced eNOS (Ser1177 and Thr496) phosphorylation. PP2 inhibited caveolin-1 and eNOS phosphorylation induced by DMT. DMT increased the Src kinase phosphorylation. Thus, LE (1%) enhanced the DMT-induced contraction by inhibition of NO synthesis, which may be caused by the decreased DMT concentration. DMT-induced NO synthesis may be caused by the increased eNOS (Ser1177) phosphorylation and decreased eNOS (Thr495) phosphorylation potentially mediated by Src kinase-induced caveolin-1 phosphorylation. [ABSTRACT FROM AUTHOR]