Eye-movement reveals word order effects on comparative sentences in older adults using a verb-final language.

Objectives: This study aimed to examine age-related differences in the comprehension of Korean comparative sentences with varying word orders by employing both offline and online measures, and to investigate how variations in word order affect sentence processing across different age groups. Methods: A total of 52 monolingual native Korean speakers, 26 young adults, and 26 older adults, completed a sentence-picture-matching task under two word order conditions: comparative-first and nominative-first. Offline measures included accuracy and response time, while an online method involved eye-tracking within the Visual World Paradigm. Data analyses were performed using linear and generalized linear mixed-effects models. Results: Older adults demonstrated lower accuracy and longer response times compared to younger individuals. Distinctive fixation patterns were observed, particularly in the sentential-final phrase, across different age groups. Specifically, nominative-first sentences elicited greater target advantage scores among younger adults, whereas older adults showed higher scores in comparative-first sentences. Conclusion: The study highlights the potential of comparative sentences in elucidating age-related changes in sentence comprehension. These differences were evident not only in offline tasks but also in real-time processing, as evidenced by eye-tracking data. The findings suggest distinct processing strategies employed by young and older adults and underscore the importance of considering both syntactic and semantic cues in sentence comprehension.

Microphysiological Blood-Brain Barrier Systems for Disease Modeling and Drug Development.

The blood-brain barrier (BBB) is a highly controlled microenvironment that regulates the interactions between cerebral blood and brain tissue. Due to its selectivity, many therapeutics targeting various neurological disorders are not able to penetrate into brain tissue. Pre-clinical studies using animals and other in vitro platforms have not shown the ability to fully replicate the human BBB leading to the failure of a majority of therapeutics in clinical trials. However, recent innovations in vitro and ex vivo modeling called organs-on-chips have shown the potential to create more accurate disease models for improved drug development. These microfluidic platforms induce physiological stressors on cultured cells and are able to generate more physiologically accurate BBBs compared to previous in vitro models. In this review, different approaches to create BBBs-on-chips are explored alongside their application in modeling various neurological disorders and potential therapeutic efficacy. Additionally, organs-on-chips use in BBB drug delivery studies is discussed, and advances in linking brain organs-on-chips onto multiorgan platforms to mimic organ crosstalk are reviewed.

Preliminary investigation of a combined herbal extract of Aruncus dioicus, Cirsium nipponicum, and Ocimum basilicum for halitosis.

BACKGROUND: Halitosis, the unpleasant odor in the oral cavity, has garnered increased attention and concern due to the growing significance of social interaction. SGE-107, a blend of 3 botanical drugs-Korean goat's beard, Cirsium tanakae, and Basil-with caffeic acid as its indicator component. This study aims to investigate the efficacy of SGE-107 in treating halitosis in patients with mild gastrointestinal symptoms. METHODS: We enrolled 25 participants with oral malodor and dyspeptic symptoms. We assessed the severity of halitosis using the visual analog scale. Throughout a 4-week period of administering SGE-107, we evaluated both objective and subjective parameters, including the halitosis-associated life-quality test, the Korean gastrointestinal symptom rating scale, levels of volatile sulfur compounds, salivary flow rate, oral moisture, tongue index, Winkel tongue coating index, and tongue temperature. RESULTS: After the intervention period, both the visual analog scale (5.88 ±â€…1.03 vs 2.38 ±â€…0.93, P < .001) and the scores of the halitosis-associated life-quality test (31.21 ±â€…11.78 vs 13.83 ±â€…6.38, P < .001) showed significant reductions. The proportion of participants with abnormal levels of methyl mercaptan (a volatile sulfur compound) also significantly decreased (17, 70.8% vs 9, 37.5%, P = .039). Furthermore, there were significant improvements in reflux, constipation, diarrhea, and the total scores on the Korean gastrointestinal symptom rating scale. Throughout the study period, only 2 participants experienced mild adverse events. CONCLUSION: SGE-107 appears to be a safe and effective treatment for halitosis-associated with gastrointestinal symptoms; nevertheless, the limited sample size necessitates further large-scale randomized, controlled studies to confirm our findings.

Microneedle patch-based enzyme-linked immunosorbent assay to quantify protein biomarkers of tuberculosis.

There is a clinical need for differential diagnosis of the latent versus active stages of tuberculosis (TB) disease by a simple-to-administer test. Alpha-crystallin (Acr) and early secretory antigenic target-6 (ESAT-6) are protein biomarkers associated with the latent and active stages of TB, respectively, and could be used for differential diagnosis. We therefore developed a microneedle patch (MNP) designed for application to the skin to quantify Acr and ESAT-6 in dermal interstitial fluid by enzyme-linked immunosorbent assay (ELISA). We fabricated mechanically strong microneedles made of polystyrene and coated them with capture antibodies against Acr and ESAT-6. We then optimized assay sensitivity to achieve a limit of detection of 750 pg/ml and 3,020 pg/ml for Acr and ESAT-6, respectively. This study demonstrates the feasibility of an MNP-based ELISA for differential diagnosis of latent TB disease.

Immobilized Candida antarctica lipase B as an sn-1,3 regiospecific biocatalyst for the interesterification of triacylglycerols with fatty acid ethyl esters.

Candida antarctica lipase B (CALB) is regarded as non-regiospecific. This study aimed to investigate the regiospecificity of CALB in the solvent-free interesterification of high-oleic sunflower oil with stearic acid ethyl ester for 1,3-distearoyl-2-oleoylglycerol (SOS)-rich fat preparation using a packed bed reactor. The content ratio of 1,2-distearoyl-3-oleoylglycerol (SSO) to SOS (denoted by SSO/SOS content) obtained using Lipozyme 435 (a commercially immobilized CALB; 0-4.1%), at residence times (1-32 min) was similar to that obtained using Lipozyme RM IM (0-3.0%), but lower than that obtained using Lipozyme TL IM (6.0-39.4%). When immobilized on Lewatit VP OC 1600, Lipozyme CALB had an SSO/SOS content of 0-10.4%, which was greater than that of Palatase 20,000 L (0-1.1%) but was lower than that of Lipozyme TL 100 L (8.8-97.7%). Our findings suggest that immobilized CALB shows distinct sn-1,3 regiospecificity in the interesterification of triacylglycerol with fatty acid ethyl esters.

The Relative Contribution of Facial and Body Information to the Perception of Cuteness.

Faces and bodies both provide cues to age and cuteness, but little work has explored their interaction in cuteness perception. This study examines the interplay of facial and bodily cues in the perception of cuteness, particularly when these cues convey conflicting age information. Participants rated the cuteness of face-body composites that combined either a child or adult face with an age-congruent or incongruent body alongside manipulations of the head-to-body height ratio (HBR). The findings from two experiments indicated that child-like facial features enhanced the perceived cuteness of adult bodies, while child-like bodily features generally had negative impacts. Furthermore, the results showed that an increased head size significantly boosted the perceived cuteness for child faces more than for adult faces. Lastly, the influence of the HBR was more pronounced when the outline of a body's silhouette was the only available information compared to when detailed facial and bodily features were presented. This study suggests that body proportion information, derived from the body's outline, and facial and bodily features, derived from the interior surface, are integrated to form a unitary representation of a whole person in cuteness perception. Our findings highlight the dominance of facial features over bodily information in cuteness perception, with facial attributes serving as key references for evaluating face-body relationships and body proportions. This research offers significant insights into social cognition and character design, particularly in how people perceive entities with mixed features of different social categories, underlining the importance of congruency in perceptual elements.

Lipase-catalyzed preparation of deacidified Buah Merah (Pandanus conoideus) oil.

Buah Merah oil (BMO) is unrefined edible oil containing a high level of free fatty acids (FFA; ∼30% w/w). This study was aimed at preparing deacidified BMO from BMO via lipase-catalyzed esterification of FFA in BMO with added glycerol, using Duolite A568-immobilized Eversa Transform 2.0 (Thermomyces lanuginosus lipase) as biocatalyst. BMO containing 2.4% w/w FFA and 94.6% w/w triacylglycerol was obtained under optimal reaction conditions (temperature, 70°C; FFA-to-glycerol molar ratio, 3:1; enzyme loading based on the protein quantity, 3.75 mg/g BMO, and reaction time, 48 h). No significant difference was found in the contents of ß-carotene, tocopherols, and phytosterols between raw and deacidified BMO. The induction period of oxidation was significantly longer in deacidified BMO (16.37 h) than in raw BMO (0.03 h). These results suggest that deacidified BMO could be enzymatically prepared without the loss of health-beneficial minor components while enhancing the oxidative stability. PRACTICAL APPLICATION: Although BMO has recently received much attention for its potential biological activities, the commercial use of BMO as a healthy oil has been limited due to its high FFA content. Unlike conventional alkali and steam refining, enzymatic deacidification of BMO employed in this study might help the commercialization of BMO, because this procedure enables the improvement of oil yield and the retaining of health-beneficial minor components.

Long-Term Survival Analysis of 5619 Total Ankle Arthroplasty and Patient Risk Factors for Failure.

BACKGROUND: Total ankle arthroplasty (TAA) has higher complication and failure rates compared to other surgical joint replacement procedures despite technological advances. This study aimed to find the long-term survivability of the TAA procedure and identify the patient risk factors for failure with one of the largest cohorts of patients in the literature. METHODS: This retrospective cohort study involving cases between 2007 and 2018 analyzed patients who received an index primary TAA procedure in Korea. A total of 5619 cases were included in the final analysis. The TAA failure was defined as either a case with revision arthroplasty or a case with TAA implant removal and arthrodesis performed after primary TAA. RESULTS: During the study period, the 5-year survival rate was 95.4% (95% CI, 94.7-96.1%), and the 10-year survival rate was 91.1% (95% CI, 89.1-93.1%). A younger age (<55 years, adjusted hazard ratio [AHR], 1.725; 55-64 years, AHR, 1.812; p < 0.001 for both), chronic pulmonary disease (AHR, 1.476; p = 0.013), diabetes (AHR, 1.443; p = 0.014), and alcohol abuse (AHR, 1.524; p = 0.032) showed a significantly high odds ratio for primary TAA failure in Cox regression analysis. CONCLUSION: The 10-year TAA survivorship rate was 91.1%. A younger age, chronic pulmonary disease, diabetes, and heavy alcohol consumption are risk factors for TAA.

Phosphorylation of XPD drives its mitotic role independently of its DNA repair and transcription functions.

The helicase XPD is known as a key subunit of the DNA repair/transcription factor TFIIH. However, here, we report that XPD, independently to other TFIIH subunits, can localize with the motor kinesin Eg5 to mitotic spindles and the midbodies of human cells. The XPD/Eg5 partnership is promoted upon phosphorylation of Eg5/T926 by the kinase CDK1, and conversely, it is reduced once Eg5/S1033 is phosphorylated by NEK6, a mitotic kinase that also targets XPD at T425. The phosphorylation of XPD does not affect its DNA repair and transcription functions, but it is required for Eg5 localization, checkpoint activation, and chromosome segregation in mitosis. In XPD-mutated cells derived from a patient with xeroderma pigmentosum, the phosphomimetic form XPD/T425D or even the nonphosphorylatable form Eg5/S1033A specifically restores mitotic chromosome segregation errors. These results thus highlight the phospho-dependent mitotic function of XPD and reveal how mitotic defects might contribute to XPD-related disorders.

Hypermethylation of PDX1, EN2, and MSX1 predicts the prognosis of colorectal cancer.

Despite numerous observations regarding the relationship between DNA methylation changes and cancer progression, only a few genes have been verified as diagnostic biomarkers of colorectal cancer (CRC). To more practically detect methylation changes, we performed targeted bisulfite sequencing. Through co-analysis of RNA-seq, we identified cohort-specific DNA methylation markers: CpG islands of the intragenic regions of PDX1, EN2, and MSX1. We validated that these genes have oncogenic features in CRC and that their expression levels are increased in correlation with the hypermethylation of intragenic regions. The reliable depth of the targeted bisulfite sequencing data enabled us to design highly optimized quantitative methylation-specific PCR primer sets that can successfully detect subtle changes in the methylation levels of candidate regions. Furthermore, these methylation levels can divide CRC patients into two groups denoting good and poor prognoses. In this study, we present a streamlined workflow for screening clinically significant differentially methylated regions. Our discovery of methylation markers in the PDX1, EN2, and MSX1 genes suggests their promising performance as prognostic markers and their clinical application in CRC patients.

Combined analysis of inorganic elements and sugars for the identification of red pepper powder containing undeclared ingredients.

This study sought to identify adulterated red pepper powder (RPP) containing undeclared ingredients, such as salts, glucose, Monascus red pigments, and other plant ingredients (e.g., wheat flour, garlic powder, onion powder) using element and sugar analysis methods. Analytical data were obtained for 66 samples of authentic RPP and 12 samples of adulterated RPP. The variables selected to identify the authenticity of RPP include Na, Cl, K, maltohexaose, and maltoheptaose, which partly or totally originate from RPP, salts, or Monascus red pigments. All the 12 samples of commercial seasoned RPP used as models of adulterated RPP and all the 20 blind samples containing ≥10% (w/w) of commercial seasoned RPP were correctly identified by applying the range of the five variables found for the authentic RPP samples. Our findings suggest that combined analyses of the above five constituents could be used to identify adulterated RPP containing undeclared ingredients. PRACTICAL APPLICATION: Adulteration of high-priced spice products, including red pepper powder (RPP), has increasingly become a public concern worldwide as it endangers consumer health and represents economic fraud. This study provides analytical methods that can accurately determine the authenticity of RPP. They would become effective means for protecting producers and suppliers against unfair competition and consumers against health threats.

ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma.

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSCmarkers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogenederived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis. [BMB Reports 2022; 55(6): 281-286].

Inhibition of the bromodomain and extra-terminal family of epigenetic regulators as a promising therapeutic approach for gastric cancer.

PURPOSE: Epigenetic dysregulation is a common characteristic of cancers, including gastric cancer (GC), and contributes to cancer development and progression. Although the efficacy of BET (an epigenetic regulator) inhibition has been demonstrated in various cancer types, predictive genetic markers of its efficacy in GC are currently lacking. Therefore, we aimed to identify markers that predict the response of BET inhibition in GC and, suggest an effective treatment regimen through combined therapy. METHODS: The effect of BET inhibition was evaluated using iBET-151, a small-molecule inhibitor of BET proteins, in a large panel (n = 49) of GC cell lines and xenograft mouse models. Comprehensive genetic information was used to identify cell lines sensitive to iBET-151. Flow cytometry, Western blotting, and colony-formation and migration assays were used to evaluate the effects of iBET-151 and/or paclitaxel. The synergistic effect of iBET-151 and paclitaxel was evaluated using an organoid model. RESULTS: We found that iBET-151 showed a modest growth-inhibitory effect in GC cells (73%, 36/49). iBET-151 inhibited tumorigenicity in vitro and significantly promoted cell cycle arrest and apoptosis. Based on comprehensive genetic information analysis in relation to BET family expression, we found that BRD4 was highly expressed in the iBET-151-sensitive cell lines. We also identified WNT5B and IRS2 as potential biomarkers that are predictive for sensitivity to iBET-151. In GC xenograft model mice, iBET-151 significantly decreased tumor volumes and Ki-67 and BRD4 expression. Combination treatment showed that iBET-151 increased the sensitivity of GC cells to paclitaxel in approximately 70% of the cell lines (34/49) tested. iBET-151 plus paclitaxel significantly promoted cell cycle arrest and apoptosis and suppressed c-Myc, Bcl-2 and Bcl-xL expression. In GC organoids, iBET-151 and paclitaxel showed a synergistic effect. CONCLUSIONS: Collectively, our data suggest that iBET-151 is a potential therapeutic agent for GC, especially in combination with paclitaxel, and that WNT5B and IRS2 may predict iBET-151 sensitivity.

Effect of processed aloe vera gel on immunogenicity in inactivated quadrivalent influenza vaccine and upper respiratory tract infection in healthy adults: A randomized double-blind placebo-controlled trial.

BACKGROUND: Aloe vera is a functional food with various pharmacological functions, including an immune-modulating effect. Until now, A. vera has never been studied as an adjuvant in influenza vaccine, and its effects on upper respiratory tract infection (URI) are unknown. PURPOSE: The objective of our study was to investigate the effect of processed A. vera gel (PAG) on immunogenicity of quadrivalent inactivated influenza vaccine and URI in healthy adults. STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial was performed. METHODS: This study was conducted in 100 healthy adults at a single center from September 2017 to May 2018. Subjects were randomly divided into a PAG group (n = 50) and a placebo group (n = 50). The enrolled subjects were instructed to ingest the study drug for 8 weeks. The participants received a single dose of quadrivalent inactivated influenza vaccine after taking the study drug for the first 4 weeks of the study. The primary endpoint was seroprotection rate against at least one viral strain at 4 weeks post-vaccination. Other outcomes were seroprotection rate at 24 weeks post-vaccination, seroconversion rate, geometric mean fold increase (GMFI) at 4 and 24 weeks post-vaccination, seroprotection rate ratio and geometric mean titer ratio (GMTR) at 4 weeks post-vaccination between PAG and placebo groups, and incidence, severity, and duration of URI. RESULTS: The European Committee for proprietary medicinal products (CPMP) evaluation criteria were met at least one in the PAG and placebo groups for all strains. However, there was no significant difference in the seroprotection rate at 4 weeks post-vaccination against all strains in both PAG and placebo groups. Among secondary endpoints, the GMFI at 4 weeks post-vaccination for the A/H3N2 was significantly higher in the PAG than in placebo group. The GMTR as adjuvant effect was 1.382 (95% CI, 1.014-1.1883). Kaplan-Meier curve analysis showed a reduction in incidence of URI (p = 0.035), and a generalized estimating equation model identified a decrease in repeated URI events (odds ratio 0.57; 95% CI, 0.39-0.83; p = 0.003) in the PAG group. CONCLUSIONS: Oral intake of PAG did not show a significant increase in seroprotection rate from an immunogenicity perspective. However, it reduced the number of URI episodes. A well-designed further study is needed on the effect of PAG's antibody response against A/H3N2 in the future.

PLEKHA8P1 Promotes Tumor Progression and Indicates Poor Prognosis of Liver Cancer.

Hepatocellular carcinoma (HCC) records the second-lowest 5-year survival rate despite the avalanche of research into diagnosis and therapy. One of the major obstacles in treatment is chemoresistance to drugs such as 5-fluorouracil (5-FU), making identification and elucidation of chemoresistance regulators highly valuable. As the regulatory landscape grows to encompass non-coding genes such as long non-coding RNAs (lncRNAs), a relatively new class of lncRNA has emerged in the form of pseudogene-derived lncRNAs. Through bioinformatics analyses of the TCGA LIHC dataset, we have systematically identified pseudogenes of prognostic value. Initial experimental validation of selected pseudogene-derived lncRNA (PLEKHA8P1) and its parental gene (PLEKHA8), a well-studied transport protein in Golgi complex recently implicated as an oncogene in both colorectal and liver cancer, indicates that the pseudogene/parental gene pair promotes tumor progression and that their dysregulated expression levels affect 5-FU-induced chemoresistance in human HCC cell line FT3-7. Our study has thus confirmed cancer-related functions of PLEKHA8, and laid the groundwork for identification and validation of oncogenic pseudogene-derived lncRNA that shows potential as a novel therapeutic target in circumventing chemoresistance induced by 5-FU.

Preparation of Low-Diacylglycerol Cocoa Butter Equivalents by Hexane Fractionation of Palm Stearin and Shea Butter.

Herein, we prepared 1,3-dipalmitoyl-2-oleoyl glycerol (POP)-rich fats with reduced levels of diacylglycerols (DAGs), adversely affecting the tempering of chocolate, via two-step hexane fractionation of palm stearin. DAG content in the as-prepared fats was lower than that in POP-rich fats obtained by previously reported conventional two-step acetone fractionation. Cocoa butter equivalents (CBEs) were fabricated by blending the as-prepared fats with 1,3-distearoyl-2-oleoyl glycerol (SOS)-rich fats obtained by hexane fractionation of degummed shea butter. POP-rich fats achieved under the best conditions for the fractionation of palm stearin had a significantly lower DAG content (1.6 w/w%) than that in the counterpart (4.6 w/w%) prepared by the previously reported method. The CBEs fabricated by blending the POP- and SOS-rich fats in a weight ratio of 40:60 contained 63.7 w/w% total symmetric monounsaturated triacylglycerols, including 22.0 w/w% POP, 8.6 w/w% palmitoyl-2-oleoyl-3-stearoyl-rac-glycerol, 33.1 w/w% SOS, and 1.3 w/w% DAGs, which was not substantially different from the DAG content in cocoa butter (1.1 w/w%). Based on the solid-fat content results, it was concluded that, when these CBEs were used for chocolate manufacture, they blended with cocoa butter at levels up to 40 w/w%, without distinctively altering the hardness and melting behavior of cocoa butter.

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human.

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

8-Epi-xanthatin induces the apoptosis of DU145 prostate carcinoma cells through signal transducer and activator of transcription 3 inhibition and reactive oxygen species generation.

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in many human cancers. We tried to find STAT3 inhibitors from natural sources and found that Xanthium fruit extracts decreased phosphorylation of STAT3-Y705. 8-Epi-xanthatin (EXT) was isolated from the extracts. When DU145 cancer cells were treated with EXT, p-STAT3-Y705 was decreased with an IC50 of 3.2 µM. EXT decreased the expression of STAT3 target genes, such as cyclin A, cyclin D1, and BCL-2, and induced PARP cleavage, indicating apoptotic cell death. Downregulation of EXT-induced p-STAT3-Y705 was rescued by pretreating DU145 cells with antioxidants, such as N-acetyl-L-cysteine (NAC), indicating that reactive oxygen species (ROS) were involved in the EXT-induced inhibition of STAT3 activation. Furthermore, we proved the association of EXT with STAT3 protein by using a drug affinity responsive target stability (DARTS) assay and a cellular thermal shift assay (CETSA). EXT inhibited proliferation of DU145 cells with a GI50 of 6 µM and reduced tumor growth in mice xenografted with DU145 cells. Immunoblotting showed that phosphorylation of STAT3-Y705 was lower in EXT-treated tumor tissue than in control tissues. Collectively, we found that EXT binds to, and inhibits, STAT3 activation and could be a lead compound for anticancer therapy.

NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells.

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATACseq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation.

Immobilized Phospholipase A1-Catalyzed Preparation of l-α-Glycerylphosphorylcholine from Phosphatidylcholine.

This study sought to prepare a cognitive enhancer l-α-glycerylphosphorylcholine (l-α-GPC) using an immobilized Lecitase Ultra (LU, phospholipase A1) to catalyze the hydrolysis of soy phosphatidylcholine (PC). Immobilization of LU on Lewatit VP OC 1600 provided the highest fixation level (83.1 g/100 g) and greatest catalytic activity achieving 100 g/100 g l-α-GPC within 20 h and was therefore selected as the optimal system for biocatalysis. Immobilization of LU increased its positional specificity compared to free LU, as shown by a decrease in the production of the phosphocholine byproduct. Under the optimal conditions determined by response surface methodology, PC was completely hydrolyzed to l-α-GPC and required a simple purification via phase separation of the biphasic media to obtain a yield of ∼26.4 g l-α-GPC from 100 g PC, with a purity of 98.5 g/100 g. Our findings suggest a possibility of using the immobilized LU as a new biocatalyst for the l-α-GPC production.