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Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αβγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.

Objectives This study investigated the impacts of exercise on irisin and fibroblast growth factor 21 (FGF-21) expression, as well as triiodothyronine (T3) and free fatty acid (FFA) levels in elderly women. Methods Thirty women aged 65 to 70 years (10 per group) were randomly assigned to aquatic exercise, land exercise, and control groups. The aquatic and land groups engaged in 3 exercise sessions per week (60 min/session) for 16 weeks. The intensity was progressively increased every 4 weeks. Results Irisin and FGF-21 levels significantly increased in the aquatic exercise group. In the post-test, the aquatic exercise group had the highest irisin levels. Significant findings were observed for irisin and FGF-21 for the main effect between aquatic and band exercise groups (p

Background : Low compliance (LC) with lifestyle modification is a very common obstacle in obesity management. The purpose of the current study was to investigate the effectiveness of obesity management according to compliance with a lifestyle-modification program. Methods : The “Change 10 Habits” program was administered four times over 12 weeks. Eighty-seven participants were divided into LC and high compliance (HC) groups for analysis after intervention. Then, to assess the program’s effectiveness based on compliance, we conducted t-tests and linear regression modeling. Results : In week 12, the scores of two dietary habits—specifically, “eat three meals regularly, adequate amount” and “do not eat after 9:00 PM”—were significantly higher in the HC group than in the LC group. Changes in leg and total body fat percentages were significantly improved in the HC group (−0.2%±0.3% vs. 0.9%±0.3%, P

Abstract A novel auxetic structure applicable to airless tire spokes is designed based on the primitive-type triply periodic minimal surface (P-TPMS) to have higher stiffness through deformation under compressive force. For becoming higher stiffness by deformation, an unit cell of auxetic structure is proposed and its characteristics according to design parameters are studied. Based on the parametric study, a rotated primitive-type auxetic structure (RPAS) is designed, and the deformative behaviors of an airless tire with the RPAS spokes are compared with a generally used honeycomb spoke. Simulation and experiment results show that the designed RPAS tire exhibits more stable behavior through higher rigidity depending on the deformation state when compressed on flat ground and obstacles. This variable stiffness characteristic of RPAS tires can be advantageous for shock absorption and prevention of large local deformations. Also, the manufacturability of the designed auxetic structure is evaluated using real rubber-based additive manufacturing processes for practical application in the tire manufacturing industry.

Abstract Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.

In recent years, vulnerabilities in industrial control systems have increased substantially. The operational environment’s availability constraints hinder penetration testing from the attacker’s perspective as a viable vulnerability management method, thereby limiting the ability to map attack flows fully. To address this, research has been focused on understanding attack techniques by analyzing vulnerability descriptions that detail the attack flow of these vulnerabilities. However, existing research faces the challenge of not fully capturing the overall meaning of sentences, as it relies on word embedding-based learning for vulnerability information. This study proposes the V2TSA model, which uses a semantic approach to extract attack technique information from vulnerability descriptions. Additionally, the study seeks to identify the most efficient attack techniques by applying a threshold of at least 10% for the similarity probability between vulnerability and attack technique descriptions. Compared to expert analysis, the proposed model effectively identifies specific attack paths associated with vulnerabilities. Moreover, the vulnerability attack information can be leveraged to implement appropriate detection and mitigation strategies.

Abstract O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.

We implement machine learning regression models to predict peak pressures of primary and secondary systems, a major safety concern in Loss Of Condenser Vacuum (LOCV) accident. We selected the Multi-dimensional Analysis of Reactor Safety-KINS standard (MARS-KS) code to analyze the LOCV accident, and the reference plant is the Korean Optimized Power Reactor 1000MWe (OPR1000). eXtreme Gradient Boosting (XGBoost) is selected as a machine learning tool. The MARS-KS code is used to generate LOCV accident data and the data is applied to train the machine learning model. Hyperparameter optimization is performed using a simulated annealing. The randomly generated combination of initial conditions within the operating range is put into the input of the XGBoost model to predict the peak pressure. These initial conditions that cause peak pressure with MARS-KS generate the results. After such a process, the error between the predicted value and the code output is calculated. Uncertainty about the machine learning model is also calculated to verify the model accuracy. The machine learning model presented in this paper successfully identifies a combination of initial conditions that produce a more conservative peak pressure than the values calculated with existing methodologies.

Abstract Parkinson’s disease (PD) is an incurable movement disorder characterized by dopaminergic cell loss, neuroinflammation, and α-synuclein pathology. Herein, we investigated the therapeutic effects of necrosulfonamide (NSA), a specific inhibitor of mixed lineage kinase domain-like protein (MLKL), in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MLKL is an executor of necroptosis, a programmed cell death pathway that causes inflammation. Repeated administration of NSA resulted in the recovery of impaired motor performance and dopaminergic degeneration. Furthermore, NSA inhibited the phosphorylation, ubiquitylation, and oligomerization of MLKL, all of which are associated with MLKL cell death-inducing activity in dopaminergic cells in the substantia nigra (SN). NSA also inhibited microglial activation and reactive astrogliosis as well as the MPTP-induced expression of proinflammatory molecules such as tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and cystatin F. Furthermore, NSA inhibited α-synuclein oligomerization and phosphorylation in the SN of MPTP-treated mice by inhibiting the activity of glycogen synthase kinase 3β and matrix metalloproteinase-3. In conclusion, NSA has anti-necroptotic, anti-inflammatory, and anti-synucleinopathic effects on PD pathology. Therefore, NSA is a potential therapeutic candidate for PD.

Objective Three-dimensional (3D)-printed titanium implants have been developed recently, but the utility is not yet proven. The aim of this study was to compare 3D-printed titanium and polyetheretherketone (PEEK) implants after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Methods Between October 2018 and September 2021, we retrospectively analyzed 83 patients who underwent single-level MIS-TLIF (3D-printed titanium, 40; PEEK, 43). Radiologic parameters were assessed with x-ray and computed tomography (CT) at postoperative 1 week, 6 months, and 1 year. Clinical status was evaluated using Oswestry Disability Index, visual analogue scale score, and Bridwell fusion grading was assessed on 6-month and 1-year postoperative CT. Results There were no differences between the 2 groups in demographics and clinical outcomes. At 1-year of follow-up, the reported 3D-printed titanium fusion grades were grade I: 77.5% (31 patients), grade II: 17.5% (7 patients), and grade III: 5% (2 patients). The PEEK fusion grades were grade I: 51.2% (22 patients), grade II: 41.9% (18 patients), and grade III: 7.0% (3 patients). For overall fusion rate (grade I + II), there was no difference between the 2 cages (95.0% vs. 93.0%, p=0.705), but grade I was reported at a higher incidence in 3D-printed titanium than PEEK (77.5% vs. 51.2%, p=0.013). There was no difference between cages based on subsidence and complications. Conclusion There were no significant differences in the overall fusion rate for MIS-TLIF surgery between 3D-printed titanium and PEEK, but the fusion grade was better in 3D-printed titanium than in PEEK. Long-term follow-up is required to verify the effectiveness.

IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgETRAP and show reduction of mast cell and IgE levels in models of food allergy.

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and its incidence is predicted to increase worldwide. Striatal dopamine depletion caused by substantia nigra (SN) degeneration is a pathological hallmark of PD and is strongly associated with cardinal motor and non-motor symptoms. Previous studies have reported that exercise increases neuroplasticity and promotes neurorestoration by increasing neurotrophic factors and synaptic strength and stimulating neurogenesis in PD. In the present study, we found that rotarod walking exercise, a modality of motor skill learning training, improved locomotor disturbances and reduced nigrostriatal degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, our exercise regimen improved MPTP-induced perturbation of adult neurogenesis in some areas of the brain, including the subventricular zone, subgranular zone, SN, and striatum. Moreover, rotarod walking activated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and induced brain-derived neurotrophic factor (BDNF) expression in these regions. The results suggest that motor skill learning training using rotarod walking improves adult neurogenesis and restores motor performance by modulating the AMPK/BDNF pathway. Therefore, our findings provide evidence for neuroprotective effects and improved neuroplasticity in PD through motor skill learning training.

Security incidents targeting control systems and the industrial internet of things (IIoT) are on the rise as attackers gain a better understanding of the nature of these systems and their increasing connectivity to information technology (IT). Every year, the number of vulnerabilities associated with these incidents increases, making it impractical to apply timely patches for all of them. The current vulnerability assessments, which are the basis for vulnerability patching, have limitations in that they do not adequately reflect the risk of exploitation in the real world after discovery and do not consider operational technology (OT) and industrial control system (ICS) environments other than IT environments. This study proposes to evaluate exploit risk in real-world environments by considering OT/ICS environments and calculating three metrics, including exploit chain risk, exploit code availability, and exploit use probability based on cyber threat information, including IIoT vulnerability data, used in OT/ICS environments. In addition, we construct exploitation scenarios in a control system environment to prioritize vulnerabilities with a high risk of exploitation based on the three metrics. We show that by assessing the risk of attackers’ intentions and exploited technologies for attacks against IIoT devices in a control system environment, we can provide defenders with comprehensive attack risk information for proactive defense.

Oral lichen planus (OLP) is a chronic inflammatory disease that is characterized by the infiltration of T cells into the oral mucosa, causing the apoptosis of basal keratinocytes. OLP is a multifactorial disease of unknown etiology and is not solely caused by the malfunction of a single key gene but rather by various intracellular and extracellular factors. Non-coding RNAs play a critical role in immunological homeostasis and inflammatory response and are found in all cell types and bodily fluids, and their expression is closely regulated to preserve normal physiologies. The dysregulation of non-coding RNAs may be highly implicated in the onset and progression of diverse inflammatory disorders, including OLP. This narrative review summarizes the role of non-coding RNAs in molecular and cellular changes in the oral epithelium during OLP pathogenesis.

Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut–lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut–lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with Bifidobacterium species. Notably, oral treatment with either Bifidobacterium pseudolongum or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of B. pseudolongum boosts pulmonary immune defense against NTM infection by driving the protective gut–lung axis in vivo.

Abstract The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p

Increasing evidence suggests a pivotal role of receptor-interacting protein kinase 1 (RIPK1), an initiator of necroptosis, in neuroinflammation. However, the precise role of RIPK1 in microglial activation remains unclear. In the present study, we explored the role of RIPK1 in lipopolysaccharide (LPS)-induced neuroinflammation and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice by using RIPK1-specific inhibitors necrostatin-1 (Nec-1) and necrostatin-1 stable (Nec-1s). Nec-1/Nec-1s or RIPK1 siRNA inhibited the production of proinflammatory molecules and the phosphorylation of RIPK1-RIPK3-MLKL and cell death in LPS-induced inflammatory or LPS/QVD/BV6-induced necroptotic conditions of BV2 microglial cells. Detailed mechanistic studies showed that Nec-1/Nec-1s exerted anti-inflammatory effects by modulating AMPK, PI3K/Akt, MAPKs, and NF-κB signaling pathways in LPS-stimulated BV2 cells. Subsequent in vivo studies showed that Nec-1/Nec-1s inhibited microglial activation and proinflammatory gene expression by inhibiting the RIPK1 phosphorylation in the brains of LPS-injected mice. Furthermore, Nec-1/Nec-1s exert neuroprotective and anti-inflammatory effects in MPTP-induced PD mice. We found that p-RIPK1 is mainly expressed in microglia, and thus RIPK1 may contribute to neuroinflammation and subsequent cell death of dopaminergic neurons in MPTP-induced PD model mice. These data suggest that RIPK1 is a key regulator of microglial activation in LPS-induced neuroinflammation and MPTP-induced PD mice.

Abstract Background Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models. Methods Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)–stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice. Results PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice. Conclusions PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.

Summary: Design of tissue-specific contrast agents to delineate tumors from background tissues is a major unmet clinical need for ultimate surgical interventions. Bioconjugation of fluorophore(s) to a ligand has been mainly used to target overexpressed receptors on tumors. However, the size of the final targeted ligand can be large, >20 kDa, and cannot readily cross the microvasculature to meet the specific tissue, resulting in low targetability with a high background. Here, we report a small and hydrophilic phenoxazine with high targetability and retention to pancreatic neuroendocrine tumor. This bioengineered fluorophore permits sensitive detection of ultrasmall (

Abstract Background Recent evidence suggests that reactive astrocytes play an important role in neuroinflammation and neurodegenerative diseases. Thus, controlling astrocyte reactivity has been suggested as a promising strategy for treating neurodegenerative diseases. In the present study, we investigated whether a matrix metalloproteinase (MMP)-8 inhibitor, M8I, could control neuroinflammation in lipoteichoic acid (LTA)-stimulated rat primary astrocytes. Methods The effects of M8I on the expression of inducible nitric oxide synthase, cytokines, and MMPs were examined in LTA-stimulated rat primary astrocytes by ELISA, RT-PCR, and Western blot analysis. The effects of M8I on reactive oxygen species (ROS) generation and phase II antioxidant enzyme expression were examined by the DCF-DA assay, RT-PCR, and Western blot analysis. The detailed molecular mechanisms underlying the anti-inflammatory and antioxidant effects of M8I were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, Western blot, and RT-PCR analysis. Results Treatment with LTA, a major cell wall component of Gram-positive bacteria, led to astrocyte activation and induced the expression of inflammatory molecules such as iNOS, COX-2, and pro-inflammatory cytokines. In addition, LTA induced the expression of MMPs such as MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 in rat primary astrocytes. Based on previous reports showing that MMP-8 plays a role as a proinflammatory mediator in microglia, we investigated whether MMP-8 is also involved in inflammatory reactions of reactive astrocytes. We found that treatment of astrocytes with M8I significantly inhibited LTA-induced expression of iNOS, TNF-α, IL-1β, IL-6, and TLR-2. In addition, M8I inhibited LTA-induced NF-κB, MAP kinase, and Akt activities, while it increased the anti-inflammatory PPAR-γ activities. Moreover, M8I showed antioxidant effects by suppressing ROS production in LTA- or H2O2-stimulated astrocytes. Interestingly, M8I increased the expression of phase II antioxidant enzymes such as hemeoxygenase-1, NQO1, catalase, and MnSOD by modulating the Nrf2/ARE signaling pathway. Conclusions The data collectively suggest the therapeutic potential of an MMP-8 inhibitor in neuroinflammatory disorders that are associated with astrocyte reactivity.

Summary: Loss of a cell's ability to terminally differentiate because of mutations is a selected genetic event in tumorigenesis. Genomic analyses of low-grade glioma have reported recurrent mutations of far upstream element-binding protein 1 (FUBP1). Here, we show that FUBP1 expression is dynamically regulated during neurogenesis and that its downregulation in neural progenitors impairs terminal differentiation and promotes tumorigenesis collaboratively with expression of IDH1R132H. Mechanistically, collaborative action between SRRM4 and FUBP1 is necessary for mini-exon splicing of the neurospecific LSD1+8a isoform. LSD1+8a was downregulated upon loss of FUBP1 in neural progenitors, thereby impairing terminal neuronal differentiation and maturation. Reinforcing LSD1+8a expression in FUBP1-downregulated neural progenitors restored terminal differentiation and suppressed tumorigenesis; hence, LSD1+8a is an obligatory effector of FUBP1-dependent neuronal differentiation. These findings establish a direct role for FUBP1 in neuronal differentiation and also explain its tumor-suppressor function in the nervous system. : In this article, Paik and colleagues demonstrate that FUBP1 plays an indispensable role in promoting terminal differentiation of neurons and that lack of FUBP1 interferes with early-born neuronal cells exiting the cell cycle and predisposes these cells for transformation. These findings explain how FUBP1 serves uniquely as a tumor suppressor in the CNS. Keywords: neural stem cell, FUBP1, LSD1, splicing, differentiation, glioma, oligodendroglioma

PURPOSE This study aims to carry out a comparative analysis of measuring methods to predict a critical power in rowers. METHODS Three types of tests were performed for seven male university rowers: 1) a critical power determination test, 2) a 3‐ and 6‐minute all‐out rowing test, 3) a 2,000 m simulated rowing test. The CP and W ́ were determined from the regression between work and time to exhaustion, derived from two exhaustive trials at 60, 70% of the maximal power, and 3‐, 6‐minute all‐out rowing test to estimate the EP and WEP. The test data were analyzed by paired t‐test, one‐way ANOVA, and Pearson correlation. RESULTS Comparing the differences between the 3‐ and 6‐minute all‐out tests, EP (p< .001) showed that the 6‐minute test was lower than the 3‐minute test and WEP (p

Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma.

Abstract Background Black ginseng (Panax ginseng C. A. Meyer), three to nine times-steamed and dried ginseng, has biological and pharmacological activities. In this study, the anti-diabetic effects of the black ginseng ethanol extract (GBG05-FF) in typical type 2 diabetic model db/db mice were investigated. Methods The effect of GBG05-FF in Type 2 diabetic mice was investigated by their blood analysis, biological mechanism analysis, and histological analysis. Results The mice group treated with GBG05-FF showed decreased fasting blood glucose and glucose tolerance compared to that of the nontreated GBG05-FF group. In the blood analysis, GBG05-FF decreased main plasma parameter such as HbA1c, triglyceride, and total-cholesterol levels related to diabetes and improved the expression of genes and protein related to glucose homeostasis and glucose uptake in the liver and muscle. The histological analysis result shows that GBG05-FF decreased lipid accumulation in the liver and damage in the muscle. Moreover, GBG05-FF increased the phosphorylation of the AMPK in the liver and upregulated the expression of GLUT2 in liver and GLUT4 in muscle. Therefore, the mechanisms of GBG05-FF may be related to suppressing gluconeogenesis by activating AMPK in the liver and affecting glucose uptake in surrounding tissues via the upregulation of GLUT2 and GLUT4 expression. Conclusion These findings provided a new insight into the anti-diabetic clinical applications of GBG05-FF and it might play an important role in the development of promising functional foods and drugs from the viewpoint of the chemical composition and biological activities.

Nuclear criticality safety analyses (NCSAs) considering burnup credit were performed for the GBC-32 cask. The used nuclear fuel assemblies (UNFAs) discharged from Hanbit Nuclear Power Plant Unit 3 Cycle 6 were loaded into the cask. Their axial burnup distributions and average discharge burnups were evaluated using the DeCART and Multi-purpose Analyzer for Static and Transient Effects of Reactors (MASTER) codes, and NCSAs were performed using SCALE 6.1/STandardized Analysis of Reactivity for Burnup Credit using SCALE (STARBUCS) and Monte Carlo N-Particle transport code, version 6 (MCNP 6). The axial burnup distributions were determined for 20 UNFAs with various initial enrichments and burnups, which were applied to the criticality analysis for the cask system. The UNFAs for 20- and 30-year cooling times were assumed to be stored in the cask. The criticality analyses indicated that keff values for UNFAs with nonuniform axial burnup distributions were larger than those with a uniform distribution, that is, the end effects were positive but much smaller than those with the reference distribution. The axial burnup distributions for 20 UNFAs had shapes that were more symmetrical with a less steep gradient in the upper region than the reference ones of the United States Department of Energy. These differences in the axial burnup distributions resulted in a significant reduction in end effects compared with the reference.

Polymers are the most commonly used material for three-dimensional (3D) printing in dentistry; however, the high porosity and water absorptiveness of the material adversely influence biofilm formation on the surface of the 3D-printed dental prostheses. This study evaluated the effects of a newly developed chlorhexidine (CHX)-loaded polydimethylsiloxane (PDMS)-based coating material on the surface microstructure, surface wettability and antibacterial activity of 3D-printing dental polymer. First, mesoporous silica nanoparticles (MSN) were used to encapsulate CHX, and the combination was added to PDMS to synthesize the antibacterial agent-releasing coating substance. Then, a thin coating film was formed on the 3D-printing polymer specimens using oxygen plasma and thermal treatment. The results show that using the coating substance significantly reduced the surface irregularity and increased the hydrophobicity of the specimens. Remarkably, the culture media containing coated specimens had a significantly lower number of bacterial colony formation units than the noncoated specimens, thereby indicating the effective antibacterial activity of the coating.

Glioblastoma (GBM) is aggressive malignant tumor residing within the central nervous system. Although the standard treatment options, consisting of surgical resection followed by combined radiochemotherapy, have long been established for patients with GBM, the prognosis is still poor. Despite recent advances in diagnosis, surgical techniques, and therapeutic approaches, the increased patient survival after such interventions is still sub-optimal. The unique characteristics of GBM, including highly infiltrative nature, hard-to-access location (mainly due to the existence of the blood brain barrier), frequent and rapid recurrence, and multiple drug resistance mechanisms, pose challenges to the development of an effective treatment. To overcome current limitations on GBM therapy and devise ideal therapeutic strategies, efforts should focus on an improved molecular understanding of GBM pathogenesis. In this review, we summarize the molecular basis for the development and progression of GBM as well as some emerging therapeutic approaches.

The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named “double-agent” genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 “double-agent” genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.

In this study, we have developed an effective amino passivation process for quantum dots (QDs) at room temperature and have investigated a passivation mechanism using a photo-assisted chemical method. As a result of the reverse reaction of the H2O molecules, the etching kinetics of the photo-assisted chemical method increased upon increasing the 3-amino-1-propanol (APOL)/H2O ratio of the etching solution. Photon-excited electron-hole pairs lead to strong bonding between the organic and surface atoms of the QDs, and results in an increase of the quantum yield (QY%). This passivation method is also applicable to CdSe/ZnSe core/shell structures of QDs, due to the passivation of mid-gap defects states at the interface. The QY% of the as-synthesized CdSe QDs is dramatically enhanced by the amino passivation from 37% to 75% and the QY% of the CdSe/ZnSe core/shell QDs is also improved by ∼28%.

In this paper, we describe a computer program, iBEST (inverse Burnup ESTimator), that we developed to accurately estimate the burnup histories of spent nuclear fuels based on sample measurement data. The burnup history parameters include initial uranium enrichment, burnup, cooling time after discharge from reactor, and reactor type. The program uses algebraic equations derived using the simplified burnup chains of major actinides for initial estimations of burnup and uranium enrichment, and it uses the ORIGEN-S code to correct its initial estimations for improved accuracy. In addition, we newly developed a stable bisection method coupled with ORIGEN-S to correct burnup and enrichment values and implemented it in iBEST in order to fully take advantage of the new capabilities of ORIGEN-S for improving accuracy. The iBEST program was tested using several problems for verification and well-known realistic problems with measurement data from spent fuel samples from the Mihama-3 reactor for validation. The test results show that iBEST accurately estimates the burnup history parameters for the test problems and gives an acceptable level of accuracy for the realistic Mihama-3 problems.

Antioxidants are used to prevent the oxidation of foods. When used for food additive purposes, the dosage should be regulated and the functionality evaluated to ensure stability. In this study, we performed a method validation for the quantitative analysis of rosemary extract residues and evaluated the antioxidant activity of rosemary extract in food matrices. The validated method was able to determine rosemary extract under the optimized high-performance liquid chromatography-photodiode array (HPLC-PDA) conditions. Furthermore, the antioxidant activity was evaluated by peroxide value, acid value, and in terms of the residual antioxidant levels in lard oil. For HPLC-PDA analysis, the limit of detection and quantification of rosemary extracts was ranged from 0.22 to 1.73 μg/mL, 0.66 to 5.23 μg/mL and the recoveries of the rosemary extracts ranged from 70.6 to 114.0%, with relative standard deviations of between 0.2% and 3.8%. In terms of antioxidant activity, carnosic acid performed better than carnosol. Furthermore, by evaluation of the residual antioxidant level using HPLC, we found that carnosic acid is more stable in lard oil than carnosol. These results indicate that rosemary extract can be used as an antioxidant and that the analytical method is suitable for the determination of rosemary extract in various food samples.

Precise regulation of gene expression is especially important for circadian timekeeping which is maintained by the proper oscillation of the mRNA and protein of clock genes and clock-controlled genes. As a main component of the core negative arm feedback loops in the circadian clock, the Cry1 gene contributes to the maintenance of behavioral and molecular rhythmicity. Despite the central role of Cry1, the molecular mechanisms regulating expression levels of Cry1 mRNA and protein are not well defined. In particular, the post-transcriptional regulation of Cry1 mRNA fate decisions is unclear. Here, we demonstrate that hnRNP Q binds to mCry1 mRNA via the 5'UTR. Furthermore, hnRNP Q inhibits the translation of mCry1 mRNA, leading to altered rhythmicity in the mCRY1 protein profile.

The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES) in the 5' untranslated region (UTR). Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5'UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes.