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Abstract Conventional methods for assessing tongue bacterial biofilms have low inter-examiner reliability due to visualization challenges. This study aimed to develop and assess a novel Tongue Biofilm Fluorescence Index (TBFI) for the accurate detection and objective evaluation of the quantitative and qualitative characteristics of tongue biofilms at the chairside. Data were collected from 81 elderly individuals (n = 162 images). Qraycam captured white-light and fluorescence images of the dorsal tongue, and two examiners assessed tongue coating (TC) using the TBFI. The TBFI was calculated based on biofilm intensity and coverage (0–2 scale). Inter-examiner agreement (Kappa) was compared with the Winkel’s Tongue Coating Index (WTCI) and the Oho Index. Validity was evaluated through correlations with hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH) levels. TBFI demonstrated the highest inter-examiner reliability (TBFI, κ = 0.752; WTCI, κ = 0.317; Oho Index, κ = 0.496), particularly for thickness rating (agreement rate: TBFI, 96.3%; WTCI, 76.5%; Oho Index, 79.6%). H₂S and CH₃SH concentrations showed significant positive correlations with all three indices, with the highest correlation observed between H₂S and TBFI (TBFI, r = 0.369; WTCI, r = 0.304; Oho Index, r = 0.308; p

Abstract Background Toothbrushing is the most commonly used method to physically remove dental plaque. However, there are many areas of the mouth that are difficult to reach with a toothbrush. The type of toothbrush is a critical factor influencing the effectiveness of oral care. The purpose of the study was to evaluate a toothbrush with a thin head, slender-neck and super-tapered bristles to target hard-to-reach areas in the oral cavity for reducing dental plaque and gingivitis. Methods This crossover study included 58 adults aged 20 years and older. All participants were randomly assigned to use test and control toothbrushes (the latter had a normal head and round bristles) for two 4-week phases. Participants brushed their teeth twice daily in their habitual manner. At the start and end of each phase the Silness-Lӧe plaque index (PI), Lӧe -Silness gingival index (GI) and bleeding-on-probing index (BOP) were assessed and performed plaque fluorescence tests using quantitative light-induced fluorescence technology. Results After using the test toothbrush, PI, GI and BOP decreased by 25%, 30% and 48%, respectively (P

Abstract This study presents a novel in vitro bilayer 3D co‐culture platform designed to obtain cancer‐associated fibroblasts (CAFs)‐like cells. The platform consists of a bilayer hydrogel structure with a collagen/polyethylene glycol (PEG) hydrogel for fibroblasts as the upper layer and an alginate hydrogel for tumor cells as the lower layer. The platform enabled paracrine interactions between fibroblasts and cancer cells, which allowed for selective retrieval of activated fibroblasts through collagenase treatment for further study. Fibroblasts remained viable throughout the culture periods and showed enhanced proliferation when co‐cultured with cancer cells. Morphological changes in the co‐cultured fibroblasts resembling CAFs were observed, especially in the 3D microenvironment. The mRNA expression levels of CAF‐related markers were significantly upregulated in 3D, but not in 2D co‐culture. Proteomic analysis identified upregulated proteins associated with CAFs, further confirming the transformation of normal fibroblasts into CAF within the proposed 3D co‐culture platform. Moreover, co‐culture with CAF induced radio‐ and chemoresistance in pancreatic cancer cells (PANC‐1). Survival rate of cancer cells post‐irradiation and gemcitabine resistance increased significantly in the co‐culture setting, highlighting the role of CAFs in promoting cancer cell survival and therapeutic resistance. These findings would contribute to understanding molecular and phenotypic changes associated with CAF activation and provide insights into potential therapeutic strategies targeting the tumor microenvironment.

Background: No study has quantitatively assessed tooth wear using a clinical quantitative light-induced fluorescence (QLF) system. This study aimed to compare fluorescence parameters (ΔFwear) between the research QLF system (QLF-D) and clinical QLF system (Qraycam Pro) and evaluate the validity of both systems in detecting dentin exposure from tooth wear. Methods: Thirty-five human molars and premolars were collected. Two blinded examiners conducted evaluations. Images from QLF-D and Qraycam Pro were captured and analyzed by the first examiner to calculate ΔFwear, representing the maximum fluorescence intensity for occlusal wear. The stage of tooth wear was determined by the second examiner using the tooth wear index (TWI). The area of interest (AOI) was determined as the cusp without defects, such as caries or fractures. Only areas mutually agreed by both examiners were included in analysis. The Kruskal-Wallis test was conducted to assess differences in ΔFwear between two devices. ROC analysis evaluated the validity of both systems in determining dentin exposure using AUROC. Results: Thirty-eight AOIs were analyzed. ΔFwear significantly increased with higher TWI scores. Median ΔFwear for TWI scores (0, 1, and 2) were 6.9 %, 10.3 %, and 24.8 %, respectively, for QLF-D, and 5.7 %, 7.7 %, and 23.9 %, respectively, for Qraycam Pro. No significant differences in ΔFwear were observed between QLF-D and Qraycam Pro for any TWI score. The AUROC for both systems was 0.95. Conclusion: ΔFwear was comparable between QLF-D and Qraycam Pro and demonstrated high validity in detecting dentin exposure. These findings support the clinical application of the QLF for quantitative tooth wear assessment.

Abstract We aimed to investigate the chemical and physical properties of nano silver fluoride sustained release orthodontic elastomerics (NSF-RE) and determine their antimicrobial and antibiofilm formation activities against Streptococcus mutans. Orthodontic elastomerics were dip-coated with NSF solution in ethyl cellulose (EC) and polyethylene glycol 6000 (PEG). The studied groups included NSF (no EC/PEG), NSF-E (EC), NSF-EP1 (EC:PEG, 4:1), and NSF-EP2 (EC:PEG, 2:1). The cumulative release of silver nanoparticles (AgNPs) and fluoride, along with the compatibility of the tensile force with orthodontic brackets, was evaluated. The antimicrobial activity was evaluated using an agar diffusion test. The inhibition of biofilm formation was evaluated using colony-forming units (CFUs), biofilm thickness, and the live/dead cell ratio. NSF-RE containing EC sustained the release of AgNPs and fluoride for > 7 days. Tensile forces were not significantly different among the groups. The inhibition zone was 2.64- and 1.31-fold larger with NSF-EP2 than that with NSF and NSF-E, respectively. NSF-EP2 was the most effective in inhibiting biofilm formation with significant reductions in CFUs, biofilm thickness, and live/dead cell ratio by 57, 86, and 96%, respectively, as compared to those in the control group. Overall, sustained release of AgNPs and fluoride by NSF-RE provides antimicrobial and antibiofilm effects against S. mutans.

Background: The 1996 Goseong forest fire, the largest recorded, prompted a debate on the potential for natural forest recovery, leading to the designation of a natural restoration research area. This study mainly aimed to demonstrate the forest's natural regenerative ability in a prefire Pinus densiflora forest that had been affected by a stand-replacing fire. To achieve this, the study tracked the key aspects of the succession process, specifically the formation of vertical structure and changes in species composition. Results: The regenerating vegetation initially passed through stages dominated by herbaceous and shrub layers, then differentiated into the canopy layer, eventually forming the early-stage forest after 20 years. Site A had developed into a forest with an average canopy height of 13.3 m and 73% coverage, while Site B was restored with a canopy height of 10 m and 27% coverage. Tree species of the genus Quercus dominated the canopy layer, occupying 99% of the tree basal area (from 17% prefire). Consequently, the prefire pine forest shifted to a Quercus-dominated forest after secondary succession. Pinus densiflora (83% of the prefire basal area) occupied only 1% after 20 years. Oak species became dominant from the initial stages of regeneration, playing a key role in shaping the early-stage forest structure. The species composition of the regenerating stands was already determined in the initial stage and closely resembled that of 20 years later. Since most species regenerated through resprouting, the understory remained dominated by pine forest companion species. Oak-associated species tended to increase in later stages. No invasive species were observed, and annual plants had low abundance. Conclusions: The study demonstrated the natural regenerative power of the forest following the fire, revealing that it takes around 20 years for a prefire pine forest to be restored an early-stage oak-dominated forest. Quercus trees, particularly Quercus variabilis and Quercus mongolica, regenerated rapidly immediately after fire, contributing to the development of the early-stage forest. Although this study was small in scale, it is a rare study conducted at permanent plots over 20 years, revealing the secondary succession process.

Abstract This in vitro study aimed to evaluate the feasibility of quantitative light-induced fluorescence (QLF) technology for detecting the presence and severity of microleakage of pit and fissure sealants. The areas of interest (AOIs) were 160 pits and fissures of 40 extracted permanent teeth. Fluorescent images were acquired using a QLF device, and the maximum fluorescence loss ΔFmax of each AOI was analyzed. After staining and cross-sectioning of the teeth, histological dye penetration was scored on a scale of 0 to 3. The relationship between ΔFmax and microleakage depth was analyzed, and the areas under the curve (AUCs) were calculated. The │ΔFmax│ increased as microleakage depth increased. The ΔFmax values of microleakage areas showed a strong significant correlation with the histological scores of dye penetration (r = − 0.72, P = 0.001). AUC analysis showed a high diagnostic accuracy for microleakage depth (AUC = 0.83–0.91). The highest AUC of 0.91 was found when differentiating the outer half microleakage of the sealant (histological score 0 vs. 1–3). QLF technology is effective in assessing the presence and severity of microleakage, suggesting its potential for noninvasive detection and monitoring of sealant microleakage in clinical settings.

Background: Distinguishing between discoloration caused by caries and organic stains is challenging for dentists in clinical settings. Biofluorescence (BF)-bleaching assesses caries lesions by evaluating BF changes after removing organic stains through dental bleaching, leaving cariogenic discoloration. This study aimed to apply BF-bleaching to a simulation model mimicking cariogenic discoloration and compare the BF color changes between organic staining and cariogenic discoloration. Methods: Thirty artificial caries lesions in bovine incisors were equally divided into three groups: non-stained (NS), organic-stained (OS), and cariogenic-stained (CS) groups. The specimens were treated with bleaching agent, then BF color of each specimen was evaluated using red BF intensity (ΔR), BF hue angle (h°), and hyperspectral BF spectrum. Results: The ΔR of CS was approximately 2.74 and 1.73 times higher than that of OS, at baseline and after bleaching for 20 min, respectively. After 20 min of bleaching, the h° of CS increased by approximately 8.1° compared to the baseline, while maintaining the red BF hue range (345‒15°). In contrast, the BF hue of OS shifted from orange (15‒45°) to yellow (45‒75°) simultaneously, and the h° change was approximately 21.9°. Both CS and OS exhibited first emission peaks near 515 nm, and CS showed second peaks in the red range (620‒780 nm). After bleaching, the first peaks were restored to the sound enamel direction (peak at 486 nm), whereas the second peaks of red BF in CS were maintained. Conclusion: Applying BF-bleaching to discolored caries lesions allowed differentiation between cariogenic discoloration and organic staining based on BF color changes.

Abstract Background The recent rising health spending intrigued efficiency and cost-based performance measures. However, mortality risk adjustment methods are still under consideration in cost estimation, though methods specific to cost estimate have been developed. Therefore, we aimed to compare the performance of diagnosis-based risk adjustment methods based on the episode-based cost to utilize in efficiency measurement. Methods We used the Health Insurance Review and Assessment Service–National Patient Sample as the data source. A separate linear regression model was constructed within each Major Diagnostic Category (MDC). Individual models included explanatory (demographics, insurance type, institutional type, Adjacent Diagnosis Related Group [ADRG], diagnosis-based risk adjustment methods) and response variables (episode-based costs). The following risk adjustment methods were used: Refined Diagnosis Related Group (RDRG), Charlson Comorbidity Index (CCI), National Health Insurance Service Hierarchical Condition Categories (NHIS-HCC), and Department of Health and Human Service-HCC (HHS-HCC). The model accuracy was compared using R-squared (R2), mean absolute error, and predictive ratio. For external validity, we used the 2017 dataset. Results The model including RDRG improved the mean adjusted R2 from 40.8% to 45.8% compared to the adjacent DRG. RDRG was inferior to both HCCs (RDRG adjusted R2 45.8%, NHIS-HCC adjusted R2 46.3%, HHS-HCC adjusted R2 45.9%) but superior to CCI (adjusted R2 42.7%). Model performance varied depending on the MDC groups. While both HCCs had the highest explanatory power in 12 MDCs, including MDC P (Newborns), RDRG showed the highest adjusted R2 in 6 MDCs, such as MDC O (pregnancy, childbirth, and puerperium). The overall mean absolute errors were the lowest in the model with RDRG ($1,099). The predictive ratios showed similar patterns among the models regardless of the subgroups according to age, sex, insurance type, institutional type, and the upper and lower 10th percentiles of actual costs. External validity also showed a similar pattern in the model performance. Conclusions Our research showed that either NHIS-HCC or HHS-HCC can be useful in adjusting comorbidities for episode-based costs in the process of efficiency measurement.

Zabelia tyaihyonii has limited distribution in the middle of the Korean Peninsula. The distribution of Z. tyaihyonii with respect to its status of distribution, habitat types, vegetational environments, flowering characteristics and productivity of seed, and physical properties of soil was evaluated. Z. tyaihyonii was found to be distributed in the open grassland, shrubland with a low density, and in understory vegetation with a sparse crown density of the limestone area. The number of flowerings and seedlings of Z. tyaihyonii tended to increase towards an open space without an overstory, whereas the seed setting rate and weight were greater towards a space with a thinly closed overstory. Thus, the most stable performance was found in regions delicately covered with vegetation. Z. tyaihyonii showed a high rate of coverage under a shallow soil condition, according to natural layering. These findings collectively suggest that while Z. tyaihyonii shows a high performance in regions covered with a thinly closed overstory, populations across all habitats need conservation, including the one found in the grassland of the limestone area where re-establishment occurs. The re-establishment and extension of the distribution caused by seed dispersion from existing distribution areas suggest that maintaining a healthy ecosystem is critical for Z. tyaihyonii.

A solar-driven photoelectrochemical (PEC) cell is emerging as one of the promising clean hydrogen generation systems. Engineering of semiconductor heterojunctions and surface morphologies of photoelectrodes in a PEC cell has been a primitive approach to boost its performance. This study presents that a molybdenum disulfide (MoS2) nanoflakes photoanode on 3-dimensional (3D) porous carbon spun fabric (CSF) as a substrate effectively enhances hydrogen generations due to sufficiently enlarged surface area. MoS2 is grown on CSFs utilizing a hydrothermal method. Among three different MoS2 coating morphologies depending on the amount of MoS2 precursor and hydrothermal growth time, film shape MoS2 on CSFs had the largest surface area, exhibiting the highest photocurrent density of 26.48 mA/cm2 and the highest applied bias photon-to-current efficiency (ABPE) efficiency of 5.32% at 0.43 VRHE. Furthermore, with a two-step growth method of sputtering and a subsequent hydrothermal coating, continuous TiO2/MoS2 heterojunctions on a porous CSF further promoted the photoelectrochemical performances due to their optimized bandgap alignments. Enlarged surface area, enhanced charge transfer, and utilization of visible light enable a highly efficient MoS2/TiO2/CSF photoanode with a photocurrent density of 33.81 mA/cm2 and an ABPE of 6.97 % at 0.87 VRHE. The hydrogen generation amount of the PEC cell with MoS2/TiO2/CSF photoanode is 225.4 μmol/L after light irradiation of 60 s.

ABSTRACTThe charge trap property of solution-processed zirconium acetylacetonate (ZAA) for solution-processed nonvolatile charge-trap memory (CTM) transistors is demonstrated. Increasing the annealing temperature of the ZAA from room temperature (RT) to 300°C in ambient, the carbon double bonds within the ZAA decreases. The RT-dried ZAA for the p-type organic-based CTM shows the widest threshold voltage shift (∆VTH ≈ 80 V), four distinct VTHs for a multi-bit memory operation and retained memory currents for 103 s with high memory on- and off-current ratio (IM,ON/IM,OFF ≈ 5Ⅹ104). The n-type oxide-based CTM (Ox-CTM) also shows a ∆VTH of 14 V and retained memory currents for 103 s with IM,ON/IM,OFF ≈ 104. The inability of the Ox-CTM to be electrically erasable is well explained with simulated electrical potential contour maps. It is deduced that, irrespective of the varied solution-processed semiconductor used, the RT-dried organic ZAA as CTL shows the best memory functionality in the fabricated CTMs. This implies that the high carbon double bonds in the low-temperature processed ZAA CTL are very useful for low-cost multi-bit CTMs in flexible electronics.

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.

In order to examine the factors that contributed to the persistence of the population, we investigated the distribution of T. petaloideum in Korea. Vegetation environment, habitat type, phenology, self-compatibility and conservation status were evaluated in the limestone area with the most stable distribution of the population. The distribution of T. petaloideum was identified in the vegetation with low crown density, traditional Korean graveyards (TKG) and the edges of TKG. Among each type of the habitat, the population distributed at the edge of the TKG had the highest number of leaves, as well as had more seed per individual. The density of mature individuals was highest in the TKG, followed by the edge and limestone vegetation of the TKG. Therefore, it was evaluated that TKG functionate not only as a major habitat but also a site of seed source. After 40 days of flowering of T. petaloideum, the seeds matured, and the estivation started from the end of July. In the beginning of September, the second emergence of leaves started. The reason for T. petaloideum’s selecting TKG as the main habitat was presumed as a combined effect of annual growth patterns of the plant and Korean custom of managing graveyards.

Single-hinge cleaved antibodies (scIgGs) in tumors damped NK cell cytotoxic activities and resulted in more aggressive tumor progression, which can be rescued by targeting the neoepitope in scIgGs with an anti-hinge antibody.

Abstract We aimed to determine whether dye-enhanced quantitative light-induced fluorescence (DEQLF), wherein porous structure of caries lesions is stained with a fluorescent dye, could quantitatively distinguish between active and inactive caries. A total of 126 bovine specimens were prepared to artificially simulate caries activity. Active caries were demineralized with 1% carbopol solution for 3 (A3), 5 (A5), and 10 days (A10). For inactive caries, half specimens in each group were remineralized with 2% NaF and reallocated into three groups (I3, I5, and I10, respectively). Wet specimens were dried with compressed air for 10 s and then dyed with 100-µM sodium fluorescein for 10 s. Fluorescence images of speicmens were captured with a QLF-digital 2 + Biluminator. Fluorescence intensity (ΔG) was measured in fluorescence images of dyed specimens. ΔG between active and inactive groups was compared using independent t-test, and ΔG among active groups (or inactive groups) were compared using ANOVA (α = 0.05). ΔG in the active groups was 33.7–59.0 higher than that in the inactive groups (P

Adlay is an annual plant known for its abundant bioactive compounds and diverse pharmacological activities. Coixol, a key component found in various parts of adlay, significantly contributes to its biological activity. This study was conducted to extract adlay sprouts and seeds using different solvents (methanol and ethanol) and extraction methods (reflux and ultrasonic extraction). The extracts were then evaluated for their total polyphenol and flavonoid contents, as well as antioxidant ability (DPPH and ABTS+). Additionally, the coixol content of these extracts was analyzed using HPLC/DAD analysis. The results showed that the extraction methods and solvents used impacted the bioactive compounds and their activities in the samples. Adlay sprouts exhibited a higher compound content and stronger antioxidant capacity than adlay seeds. Moreover, a substantial amount of coixol was found in the sprouts, while it was not detected in the seeds. This study emphasizes the importance of selecting appropriate extraction methods to optimize the biological activities of adlay sprouts and seeds. Adlay sprouts, with their enriched phytochemical compounds and enhanced antioxidant ability, could serve as a valuable material for health product applications.

Abstract Miniature pigs are an ideal animal model for translational research to evaluate stem cell therapies and regenerative applications. While the derivation of induced pluripotent stem cells (iPSCs) from miniature pigs has been demonstrated, there is still a lack of a reliable method to generate and maintain miniature pig iPSCs. In this study, we derived iPSCs from fibroblasts of Wisconsin miniature swine (WMS), Yucatan miniature swine (YMS), and Göttingen minipigs (GM) using our culture medium. By comparing cells of the different pig breeds, we found that YMS fibroblasts were more efficiently reprogrammed into iPSCs, forming colonies with well-defined borders, than WMS and GM fibroblasts. We also demonstrated that YMS iPSC lines with a normal pig karyotype gave rise to cells of the three germ layers in vitro and in vivo. Mesenchymal stromal cells expressing phenotypic characteristics were derived from established iPSC lines as an example of potential applications. In addition, we found that the expression level of the switch/sucrose nonfermentable component BAF60A regulated by STAT3 signaling determined the efficiency of pig iPSC generation. The findings of this study provide insight into the underlying mechanism controlling the reprogramming efficiency of miniature pig cells to develop a viable strategy to enhance the generation of iPSCs for biomedical research.

Glioblastoma (GBM) is a representative malignant brain tumor characterized by a dismal prognosis, with survival rates of less than 2 years and high recurrence rates. Despite surgical resection and several alternative treatments, GBM remains a refractory disease due to its aggressive invasiveness and resistance to anticancer therapy. In this report, we explore the role of fibronectin type III domain containing 3B (FNDC3B) and its potential as a prognostic and therapeutic biomarker in GBM. GBM exhibited a significantly higher cancer-to-normal ratio compared to other organs, and patients with high FNDC3B expression had a poor prognosis (p < 0.01). In vitro studies revealed that silencing FNDC3B significantly reduced the expression of Survivin, an apoptosis inhibitor, and also reduced cell migration, invasion, extracellular matrix adhesion ability, and stem cell properties in GBM cells. Furthermore, we identified that FNDC3B regulates PTEN/PI3K/Akt signaling in GBM cells using MetaCore integrated pathway bioinformatics analysis and a proteome profiler phospho-kinase array with sequential western blot analysis. Collectively, our findings suggest FNDC3B as a potential biomarker for predicting GBM patient survival and for the development of treatment strategies for GBM.

Abstract Background 4-hexylresorcinol (4HR) has been shown to have anti-oxidant activity similar to that of resveratrol. As resveratrol increases sirtuin (SIRT) activity, 4HR might behave similarly to resveratrol. Method In this study, the expression levels of SIRT1, SIRT3, and SIRT6 were evaluated after 4HR administration (1–100 μM). As NAD+ is a substrate for SIRTs, its levels with SIRT activity were also studied. Results In the results, SIRT3 (100 μM at 24 h) and SIRT6 (1–100 μM at 24 h and 10 μM at 8 h) were shown to have significantly higher expression levels compared to untreated control (p < 0.05). Pan-SIRT activity and the NAD+ level was significantly increased compared to that of the untreated control (p < 0.05; 10 and 100 μM at 24 h). Conclusion 4HR administration increased SIRT activity and the NAD+ level in Saos-2 cells.

Abstract Although Krüppel-associated box domain-containing zinc-finger proteins (K-ZNFs) may be associated with sophisticated gene regulation in higher organisms, the physiological functions of most K-ZNFs remain unknown. The Zfp212 protein was highly conserved in mammals and abundant in the brain; it was mainly expressed in the cerebellum (Cb). Zfp212 (mouse homolog of human ZNF212) knockout (Zfp212-KO) mice showed a reduction in survival rate compared to wild-type mice after 20 months of age. GABAergic Purkinje cell degeneration in the Cb and aberrant locomotion were observed in adult Zfp212-KO mice. To identify genes related to the ataxia-like phenotype of Zfp212-KO mice, 39 ataxia-associated genes in the Cb were monitored. Substantial alterations in the expression of ataxin 10, protein phosphatase 2 regulatory subunit beta, protein kinase C gamma, and phospholipase D3 (Pld3) were observed. Among them, Pld3 alone was tightly regulated by Flag-tagged ZNF212 overexpression or Zfp212 knockdown in the HT22 cell line. The Cyclic Amplification and Selection of Targets assay identified the TATTTC sequence as a recognition motif of ZNF212, and these motifs occurred in both human and mouse PLD3 gene promoters. Adeno-associated virus-mediated introduction of human ZNF212 into the Cb of 3-week-old Zfp212-KO mice prevented Purkinje cell death and motor behavioral deficits. We confirmed the reduction of Zfp212 and Pld3 in the Cb of an alcohol-induced cerebellar degeneration mouse model, suggesting that the ZNF212–PLD3 relationship is important for Purkinje cell survival.

Recently, there has been a growing interest in the consumption of plant-based foods such as vegetables and grains for the purpose of disease prevention and treatment. Adlay seeds contain physiologically active substances, including coixol, coixenolide, and lactams. In this study, adlay sprouts were cultivated and harvested at various time points, specifically at 3, 5, 7, 9, and 11 days after sowing. The antioxidant activity of the extracts was evaluated using assays such as DPPH radical scavenging, ABTS radical scavenging, reducing power, and total polyphenol contents. The toxicity of the extracts was assessed using cell culture and the WST-1 assay. The aboveground components of the sprouts demonstrated a significant increase in length, ranging from 2.75 cm to 21.87 cm, weight, ranging from 0.05 g to 0.32 g, and biomass, ranging from 161.4 g to 1319.1 g, as the number of days after sowing advanced, reaching its peak coixol content of 39.38 mg/g on the third day after sowing. Notably, the antioxidant enzyme activity was highest between the third and fifth days after sowing. Regarding anti-inflammatory activity, the inhibition of cyclooxygenase 2 (COX-2) expression was most prominent in samples harvested from the ninth to eleventh days after sowing, corresponding to the later stage of growth. While the overall production mass increased with the number of days after sowing, considering factors such as yield increase index per unit area, turnover rate, and antioxidant activity, harvesting at the early growth stage, specifically between the fifth and seventh days after sowing, was found to be economically advantageous. Thus, the quality, antioxidant capacity, and anti-inflammatory activity of adlay sprouts varied depending on the harvest time, highlighting the importance of determining the appropriate harvest time based on the production objectives. This study demonstrates the changes in the growth and quality of adlay sprouts in relation to the harvest time, emphasizing the potential for developing a market for adlay sprouts as a new food product.

Abstract Background Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheet formation could improve differentiation efficiency and graft survival. Methods Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1, and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency was confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPC suspension was injected by portal vein (PV), and IPC sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation, and hepatotoxicity with IPC injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging. Results Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. Immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin at 1, 2, and 4 weeks after IPC transplantation. Conclusions In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

Abstract Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between (1) lean and obese ACs, (2) lean and obese preACs, (3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-α and IL-1β, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

Cancer treatment: turning the tide against colon cancer Drugs that target a specific subset of immune cells could render colorectal tumors more susceptible to immunological destruction by the host. The cellular composition of a tumor profoundly affects the odds of progression or survival, and some immune cell types can stall the antitumor response rather than strengthening it. Researchers led by Yong Beom Cho of Sungkyunkwan University, Seoul, South Korea, explored the impact of various subpopulations of macrophages, cells that help coordinate the immune counterattack against cancer. The researchers learned that the relative balance between M2 and M1 subtypes of macrophages correlates with colorectal cancer outcomes, patients with less M2 and more M1 activity generally faring better. They also uncovered a strategy for inhibiting M2 activity, which unleashes a more-aggressive response against the tumor and could thus offer a useful therapeutic approach.

Abstract Background The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined. Methods A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child–Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables. Results A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063). Conclusions MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.

As the semiconductor industry has grown tremendously over the last decades, its environmental impact has become a growing concern, including the withdrawal of fresh water and the generation of harmful wastewater. Tetramethylammonium hydroxide (TMAH), one of the toxic compounds inevitably found in semiconductor wastewater, should be removed before the wastewater is discharged. However, there are few affordable technologies available to remove TMAH from semiconductor wastewater. Therefore, the objective of this study was to compare different treatment options, such as Membrane Capacitive Deionization (MCDI), Reverse Osmosis (RO), and Nanofiltration (NF), for the treatment of semiconductor wastewater containing TMAH. A series of bench-scale experimental setups were conducted to investigate the removal efficiencies of TMAH, TDS, and TOC. The results confirmed that the MCDI process showed its great ability as well as RO to remove them, while the NF could not make a sufficient removal under identical recovery conditions. MCDI showed higher removals of monovalent ions, including TMA+, than divalent ions. Moreover, the removal of TMA+ by MCDI was higher under the basic solution than under both neutral and acidic conditions. These results were the first to demonstrate that MCDI has significant potential for treating semiconductor wastewater that contains TMAH.

There is increasing interest in membrane systems powered by renewable energy sources, including solar and wind, that are suitable for decentralized water supply in islands and remote regions. These membrane systems are often operated intermittently with extended shutdown periods to minimize the capacity of the energy storage devices. However, relatively little information is available on the effect of intermittent operation on membrane fouling. In this work, the fouling of pressurized membranes under intermittent operation was investigated using an approach based on optical coherence tomography (OCT), which allows non-destructive and non-invasive examination of membrane fouling. In reverse osmosis (RO), intermittently operated membranes were investigated by OCT-based characterization. Several model foulants such as NaCl and humic acids were used, as well as real seawater. The cross-sectional OCT images of the fouling were visualized as a three-dimensional volume using Image J. The OCT images were used to quantitatively measure the thickness of foulants on the membrane surfaces under different operating conditions. The results showed that intermittent operation retarded the flux decrease due to fouling compared to continuous operation. The OCT analysis showed that the foulant thickness was significantly reduced by the intermittent operation. The decrease in foulant layer thickness was found to occur when the RO process was restarted in intermittent operation.

Background: The efficacy of low-dose rate ionizing radiation (LDRIR) for antiinflammatory treatment has been confirmed in various clinical studies. However, the radiobiological mechanisms involved in the anti-inflammatory action of LDRIR have not been completely elucidated. Materials and Methods: This study investigated whether LDRIR at 0.5 or 1 Gy affected the regulation of cytokine messenger RNA expression and protein levels in inflamed synoviocytes and chondrocytes induced by lipopolysaccharide. Intercellular adhesion molecule-1, interleukin-6, interleukin-8, and growth-regulated alpha protein expression were analyzed in synoviocytes and chondrocytes at 24 h after lipopolysaccharide treatment using reverse transcription polymerase chain reaction, immunostaining, Western blotting, and enzyme-linked immunosorbent assays. Results: The messenger RNA expression levels of interleukin-6, interleukin-8, and growth-regulated alpha protein were lower in synoviocytes cotreated with lipopolysaccharide and 0.5 or 1 Gy radiation than in those treated with lipopolysaccharide alone. The immunostaining results showed that all target cytokines were downregulated after 0.5 and 1 Gy of radiation in inflamed synoviocytes and chondrocytes. In chondrocytes, all four cytokines were significantly downregulated at a dose rate of 0.053 Gy/min, and the extent of regulation was similar to that at 4.02 Gy/min. Conclusion: Our findings indicate that LDRIR may regulate pro-inflammatory cytokine expression in both synoviocytes and chondrocytes, regardless of the dose rate. Therefore, LDRIR can alleviate concerns of carcinogenesis and may be useful in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Some previous studies reported hearing ability can be reduced by impaired masticatory ability, but there has been little evidence reported of an association between hearing loss and unilateral mastication. Therefore, this study aimed to investigate the relationship between unilateral mastication (UM), estimated from individual functional tooth units (FTUs), and hearing loss in a representative sample of Korean adults. Methods: The analyzed data were obtained from 1,773 adults aged 40–89 years who participated in Korean national survey. Hearing loss was defined as a pure-tone average of >25 dB at frequencies of 0.5, 1, 2, and 4 kHz in either ear. In each subject, UM was calculated as the difference in the sums of the FTU scores, which is an index of posterior tooth occlusion, on the two sides of the oral cavity. The scores were used to classify the UM into low, moderate, and high. The adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated in multivariable logistic regression analyses. Results: When controlling for sociodemographic factors, the aOR for hearing loss was 3.12 (95% CI, 1.21–8.03) for high UM relative to low UM. This association remained in a fully-adjusted model containing factors related to noise exposure (aOR 2.88; 95% CI, 1.12–7.46). Conclusion: Adults with high UM as measured using FTUs showed a higher occurrence of hearing loss than those with low UM.

Abstract Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM‐induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow‐derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non‐T1DM donors and further identified a mechanism involving bone morphogenetic protein‐6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non‐T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin‐induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM‐assocaited bone loss. Stem Cells Translational Medicine 2019;8:522–534

Isolating a large quantity of high-quality human islets is a prerequisite for diabetes research. Human islets are typically isolated from the pancreases of brain-dead donors, making research difficult due to low availability. Pancreas tissue discarded after surgical resection may be a good alternative source of islet cells. To test this hypothesis, we isolated islets from discarded surgical specimens and evaluated the islet yield and quality as well as islet cell preparations. Eighty-two segmental pancreases were processed using the Ricordi automated method, and islet yield and quality were investigated. The mean age of patients was 54.6, and the cohort included 32 diabetes patients. After purification, partially resected pancreases yielded an average of 59,593 ± 56,651 islet equivalents (IEQs) and 2546 IEQ/g of digested pancreas, with 71.5 ± 21% purity. Multivariate analysis revealed that diabetes (p = 0.0046) and the lobe used (p = 0.0156) significantly altered islet yield. Islets transplanted into diabetic mice displayed good viability and in vitro glucose responses, DNA/RNA quality, mitochondrial function, and glucose control, even though these results were dependent on islet quality. Isolated cells also maintained high viability and function even after cryopreservation. Our findings indicate that pancreatic tissue discarded after surgery can be a valuable source of islets for diabetes research.

Human-induced pluripotent stem cell- (iPSC-) derived insulin-producing cells (IPCs) can be used for islet cell transplantation into type 1 diabetic patients and as patient-specific cells for the development of novel antidiabetic drugs. However, a method is needed to generate functional IPCs from iPSCs and simplify the protocol. We compared combinations of small molecules that could induce the differentiation of cells into a definitive endoderm and preferentially into islet precursor cells. When generated using an optimal combination of small molecules, IPCs secreted insulin in response to glucose stimulation. We constructed spheroid IPCs and optimized the culture and maturation conditions. Quantitative PCR revealed that the expression of definitive endoderm-specific markers differed depending on the combination of the small molecules. The small molecule, N-[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methylene]-4-(phenylmethyl)-1-piperazinamine, induced the differentiation of cells into functional IPCs by inhibiting Sonic hedgehog signaling. Images of the 2D culture showed that IPCs formed spheroids from day 5 and continuously secreted insulin. We developed a simple differentiation method using small molecules that produced functional IPCs that responded to glucose stimulation within a relatively short period. We posit that this method along with further refinement of the differentiation process can be applied to culture IPCs that can be used in clinical trials.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Introduction Obesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.Research design and methods We performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).Results Seven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.Conclusions Our finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.

Objective Esterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment.Research design and methods This study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. β-Cell mass and vascular densities were assessed by immunohistochemistry.Results The EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet.Conclusions The findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus.