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Objective: There have been inconsistencies in the evidence for a role of dietary patterns in the development of breast cancer. In this study, we used a large-scale cohort [Korean Cancer Prevention Study-II (KCPS-II)] to examine the association between dietary patterns and breast cancer risk in Korean women. Materials and Methods: The dietary patterns of 14,807 women from the KCPS-II were derived by factor analysis and 135 cases of breast cancer were diagnosed during the follow-up period. Cox proportional models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of breast cancer. Results: The following three major dietary patterns were identified: “Korean dietary pattern” (high intake of Kimchi, vegetables, and rice); “sweet dietary pattern” (high intake of soda and sugar); and “new (Western-like) dietary pattern” (high intake of dairy products, eggs, oil, fruits, and bread). After adjusting for potential confounders, neither the Korean (HR for the highest compared with the lowest tertile, 1.04; 95% CI 0.53−2.06) nor the sweet dietary patterns were associated with the risk of breast cancer. In contrast, the new (Western-like) dietary pattern was found to be significantly associated with an increased risk of breast cancer with an HR (95% CI) of 1.01 (0.65−1.60) for the second tertile and 1.61 (1.04−2.50) for the third tertile as compared with the lowest tertile. After stratifying by menopausal status, these effects were only statistically significant among premenopausal women for the third tertile, compared with those in the bottom tertile (HR 1.69; 95% CI 1.06−2.68; p = 0.028). No significant association was observed between the Korean or sweet dietary pattern and breast cancer among either pre- or postmenopausal women. Conclusion: Our findings revealed that a greater consumption of a new (Western-like) diet was associated with an increased breast cancer risk and consequently offer a potential prevention strategy for Korean women.

Abstract The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient’s primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1–5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value

Chikungunya fever, a viral illness transmitted to humans through the bites of infected mosquitoes, presents with symptoms such as high fever, severe myalgia, headache, arthralgia, rash, and vomiting. This disease predominantly manifests in Southeast Asia, Africa, and Central and South America, with a limited occurrence in Northeast Asia. To date, no such a documented case has been reported in South Korea. Herein, we present the first adolescent case of chikungunya fever in South Korea following a travel to Bali, Indonesia.

Abstract The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p

The potential anti-obesity effects of sea cucumber extract have been reported. However, the individual saponins responsible for these effects are yet to be isolated and characterized. This study aimed to identify the most effective sea cucumber body part for inhibiting lipid accumulation in adipocytes and to elucidate the compounds responsible for this effect using nuclear magnetic resonance (NMR) techniques. Sea cucumber ovary 80 % ethanol extract (SCOE) demonstrated remarkable efficacy in inhibiting adipocyte differentiation compared to other sea cucumber body parts with 50 % or 80 % ethanol extracts. SCOE anti-obesity effect was evaluated in C57BL/6 mice fed a high-fat diet, which revealed significant reductions in body weight, serum lipids, adipose tissue, and liver weight. Using column chromatography, eight saponins were isolated from the SCOE, four of which exhibited potent inhibitory effects on adipocyte differentiation. Of these, three active saponins, holotoxins A, B, and D1, were newly identified. These findings highlight the potential of SCOE and its saponins as effective anti-obesity agents.

We previously demonstrated that consumption of U.S.-grown sugar kelp (Saccharina latissima) prohibits inflammation and fibrosis in the liver and white adipose tissue in male diet-induced obesity (DIO) mice. This study investigated whether sugar kelp can elicit similar benefits in female DIO mice. Male and female C57BL/6J mice were fed a low-fat (LF) control, a high-fat/high-sucrose/high-cholesterol (HF) control, or HF containing 6% sugar kelp (HF-Kelp) for 16 weeks. Body weight gain, serum triglyceride and total lipids, and glucose intolerance were decreased in male HF-Kelp compared with HF control. Furthermore, sugar kelp decreased gonadal white adipose tissue (gWAT) weight with smaller adipocytes and total body fat in males. In gWAT, male HF-Kelp exhibited less inflammation and fibrosis than the HF control, confirmed by histological analysis. Moreover, HF-Kelp increased physical activity only in males. Gut microbiome analysis showed sugar kelp elevated observed species and altered beta diversity in both males and females, suggesting changes in the gut microbiome may contribute to the effects of sugar kelp on gWAT inflammation and fibrosis. Therefore, our results demonstrate that sugar kelp consumption prevents obesity-induced inflammation and fibrosis in WAT in male mice, which is attributed, at least in part, to modest increases in metabolic rates, energy expenditure, and physical activity, and also modulating the gut microbiota.

The consumption of seaweed products has gained the public's attention due to various bioactive compounds therein, which are known to have health benefits in obesity-associated metabolic disturbances, cardiovascular diseases, hyperglycemia, and insulin resistance. This review discusses the biological functions of bioactive compounds, such as peptides, polyphenols (phlorotannins and bromophenols), polysaccharides (alginate, fucoidans, laminarin), carotenoids (fucoxanthin), and phytosterols, abundant in Undaria pinnatifida (Sea Mustard, Miyeok, Wakame), Saccharina japonica (formerly Laminaria japonica; Kelp, Dasima, Kombu), and Saccharina latissima (Sugar kelp). Although seaweed products show promising preventive and therapeutic effects of seaweed products, it is crucial to consider potential health risks. Therefore, this review addresses health concerns related to heavy metal contamination and high iodine contents, particularly associated with the consumption of brown seaweed.

Abstract Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.

Abstract Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against l-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpD A162D in C. glutamicum TP851 strain with two copies of trpD A162D in the genome led to the production of 3.1 g/L l-tryptophan in flask culture. Subsequent step for l-tryptophan chlorination into 7-chloro-l-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-l-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-l-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the l-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.

Histone deacetylase 4 (HDAC4), a class IIa HDAC, has gained attention as a potential therapeutic target in treating inflammatory and metabolic processes based on its essential role in various biological pathways by deacetylating non-histone proteins, including transcription factors. The activity of HDAC4 is regulated at the transcriptional, post-transcriptional, and post-translational levels. The functions of HDAC4 are tissue-dependent in response to endogenous and exogenous factors and their substrates. In particular, the association of HDAC4 with non-histone targets, including transcription factors, such as myocyte enhancer factor 2, hypoxia-inducible factor, signal transducer and activator of transcription 1, and forkhead box proteins, play a crucial role in regulating inflammatory and metabolic processes. This review summarizes the regulatory modes of HDAC4 activity and its functions in inflammation, insulin signaling and glucose metabolism, and cardiac muscle development.

The genus Parens comprises small moths, with a wingspan of 9–13 mm, belonging to the family Erebidae. Until now, only four species have been described worldwide. In Korea, only one species, P. occi (Fibiger & Kononenko, 2008) has been known to date. In this study, a new species from Korea, P. fibigerina Lee & Byun, sp. nov., is described. As a result, two Parens species are now known from Korea. Figures of adults, male and female genitalia, and a key to the species of Parens in Korea are provided.

Liocrobyla Meyrick, 1916 is a relatively small genus within the family Gracillariidae, consisting of nine species worldwide, including five species in Korea.In this study, we recognise five species belonging to the genus Liocrobyla Meyrick, 1916 from Korea. Amongst them, one species, L. indigofera Liu, Wang & Wang, 2018, is reported for the first time in Korea. Figures of adults, male and female genitalia, along with a key to the species of Liocrobyla in Korea, are provided.

Abstract Background Bladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker. Methods We designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35–69 were randomly selected and divided into two sets by recruitment organizations [set 1, BLCA (n = 35) vs. control (n = 35); set 2, BLCA (n = 31) vs. control (n = 31)]. Baseline serum samples were analyzed by non-targeted metabolomics profiling, and OPLS-DA and network analysis were performed. Calculated genetic risk score (GRS) for BLCA from all KCPS participants was utilized for interpreting metabolomics data. Results Critical metabolic signatures shown in the BLCA group were dysregulation of lysine metabolism and tryptophan-indole metabolism. Furthermore, the prediction model consisting of metabolites (lysine, tryptophan, indole, indoleacrylic acid, and indoleacetaldehyde) reflecting these metabolic signatures showed mighty BLCA predictive power (AUC: 0.959 [0.929–0.989]). The results of metabolic differences between GRS-high and GRS-low groups in BLCA indicated that the pathogenesis of BLCA is associated with a genetic predisposition. Besides, the predictive ability for BLCA on the model using GRS and five significant metabolites was powerful (AUC: 0.990 [0.980–1.000]). Conclusion Metabolic signatures shown in the present research may be closely associated with BLCA pathogenesis. Metabolites involved in these could be predictive biomarkers for BLCA. It could be utilized for early diagnosis, prognostic diagnosis, and therapeutic targets for BLCA.

Background: The objective of this study was to evaluate how effectively the bioelectric toothbrush can alleviate dentin hypersensitivity (DHS) by using electrostatic forces to remove biofilm from the tooth surface. Methods: This study divided inpatients of a preventative dental clinic between March and October 2023 into the following two groups: a bioelectric toothbrush group (BET, n = 25) and a non-bioelectric toothbrush group (NBET, n = 18) as a control group. This was a randomized double-blind, placebo-controlled trial study. A survey, the number of hypersensitive teeth, the O’Leary index, the visual analogue scale (VAS), and the Schiff Cold Air Sensitivity Scale (SCASS) were also investigated. Results: When fluoride toothpaste was applied with a bioelectric toothbrush, the subjects’ VAS and SCASS scores reflecting symptoms of hyperesthesia significantly decreased over time, as did the number of hypersensitive teeth and the O’Leary index. Moreover, the bioelectric toothbrush was confirmed to be effective in removing dental plaque. Conclusions: Dental clinics must actively promote bioelectric toothbrushes and fluoride toothpaste for patients suffering from hyperesthesia and pain. Furthermore, these items can be suggested as preventative oral care products to patients with potential hyperesthesia.

PURPOSE This study aimed to compare body composition, physical fitness, maximum muscle strength, and blood lactate concentration according to the level of aerobic capacity in Keirin cyclists. METHODS Forty-four Keirin cyclists participated in this study and were divided into three groups: the top 20% VO2max group (TG, n=9), the middle 20% VO2max group (MG, n=9), and the low 20% VO2max group (LG, n=9). The study measured body composition, physical fitness, maximum muscle strength, and blood lactate concentration in Keirin cyclists. Differences between groups were determined using one-way ANOVA analysis. RESULTS Body weight, percentage of body fat, and body mass index were significantly higher in the LG than in the TG and MG. The vertical jump and maximum muscle strength were significantly higher in the TG and MG than in the LG. Additionally, blood lactate concentrations immediately after exhaustive exercise and during the 5-minute recovery periods were higher in the LG than in the TG and MG. Moreover, the time to exhaustion, HRmax and maximum power were the highest in the TG. CONCLUSIONS Our findings suggest new information that levels of aerobic capacity in male Keirin cyclists might be a crucial predictor of cycling performance and recovery ability.

PURPOSE This study aimed to investigate whether endurance and resistance training sequences and circadian rhythms affect muscle hypertrophy and mitochondrial biogenesis-related molecules in obese rats. METHODS Rats were randomly divided into five groups: the obesity control group (OCG), aerobic-resistance exercise in the morning group (ARMG), resistance-aerobic exercise in the morning group (RAMG), aerobic resistance exercise in the evening group (AREG), and resistance-aerobic exercise in the evening group (RAEG). The exercise groups performed endurance and resistance exercises for 8 weeks according to their circadian rhythms and exercise sequences. RESULTS We evaluated specific muscle hypertrophy and mitochondrial biogenesis markers in the flexor pollicis longus and soleus muscles using western blot and immunofluorescence techniques. The body weight was significantly decreased in the ARMG, RAMG, AREG, RAEG compared to the OCG after intervention. The soleus muscle fiber cross-sectional area and muscle hypertrophy markers p-Akt and p-mTOR were significantly increased in the AREG group compared with those in the OCG, ARMG, RAMG, and RAEG groups after exercise intervention. Most mitochondrial biogenesis-related markers were significantly increased in the RAMG group than in the other groups after exercise intervention. CONCLUSION Our findings provide new evidence that muscle hypertrophy might be upregulated by resistance exercise after evening endurance exercise. In addition, morning resistance exercise followed by aerobic exercise, might promote mitochondrial biogenesis.

Abstract In grafted apple, rootstock-derived signals influence scion cold tolerance by initiating physiological changes to survive over the winter. To understand the underlying molecular interactions between scion and rootstock responsive to cold, we developed transcriptomics and metabolomics data in the stems of two scion/rootstock combinations, ‘Gala’/‘G202’ (cold resistant rootstock) and ‘Gala’/‘M9’ (cold susceptible rootstock). Outer layers of scion and rootstock stem, including vascular tissues, were collected from the field-grown grafted apple during the winter. The clustering of differentially expressed genes (DEGs) and gene ontology enrichment indicated distinct expression dynamics in the two graft combinations, which supports the dependency of scion cold tolerance on the rootstock genotypes. We identified 544 potentially mobile mRNAs of DEGs showing highly-correlated seasonal dynamics between scion and rootstock. The mobility of a subset of 544 mRNAs was validated by translocated genome-wide variants and the measurements of selected RNA mobility in tobacco and Arabidopsis. We detected orthologous genes of potentially mobile mRNAs in Arabidopsis thaliana, which belong to cold regulatory networks with RNA mobility. Together, our study provides a comprehensive insight into gene interactions and signal exchange between scion and rootstock responsive to cold. This will serve for future research to enhance cold tolerance of grafted tree crops.

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds.

ObjectiveTo investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo.MethodsCaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot.ResultsENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined.ConclusionThe combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

As a carotenoid originally used as a pigment in the aquaculture industry, astaxanthin is gaining interest in food, nutritional, and biopharmaceutical sciences in recent years due to its great antioxidant and anti-inflammatory properties, as well as its health effects on diabetes, cardiovascular diseases, cancer, and so on. However, the poor chemical stability and water solubility make practical applications of astaxanthin on human health become challenging. Nanoencapsulation of astaxanthin is considered a possible solution to tackle such challenges by improving chemical stability, and providing controlled release, thus enhancing its bioaccessibility and bioavailability. In this article, an updated overview of the chemistry, sources, and extraction methods of astaxanthin is provided. Moreover, recent studies on the health effects of astaxanthin were introduced and then the recent progress on the preparation of various nanoparticles for the encapsulation of astaxanthin are highlighted. This perspective article aims to provide guidance on potential structural designs of nanoparticles for the encapsulation of astaxanthin and the effects of nanoencapsulation on its functionality.

ABSTRACTThe prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.

Abstract Background In the US, stimulant use is associated with a 3–6 times greater rate of HIV seroconversion in sexual minority men (SMM) than in those who do not use stimulants. Annually, 1 in 3 SMM who HIV seroconvert will be persistent methamphetamine (meth) users. The primary objective of this qualitative study was to explore experiences of stimulant use in SMM living in South Florida, a high priority region for the Ending the HIV Epidemic initiative. Methods The sample included 25 SMM who use stimulants, recruited via targeted ads on social networking apps. Participants completed one-on-one semi-structured qualitative interviews, conducted from July 2019 through February 2020. A general inductive approach was used to identify themes relating to experiences, motivations, and overall relationship with stimulant use. Results Mean age of participants was 38.8, ranging from 20 to 61 years old. Participants were 44% White, 36% Latino, 16% Black and 4% Asian. Most participants were born in the US, self-identified as gay, and preferred meth as their stimulant of choice. Themes included: (1) stimulants as cognitive enhancements for focus or task completion, including transitioning to meth after first using prescription psychostimulants; (2) unique South Florida environment where participants could be open regarding their sexual minority status while also being influential on their stimulant use; (3) stimulant use as both stigmatizing and a coping mechanism for stigma. Participants anticipated stigma by family and potential sexual partners due to their stimulant use. They also reported using stimulants to cope with feelings of stigma due to their minoritized identities. Conclusion This study is among the first to characterize motivations for stimulant use in SMM living in South Florida. Results highlight both the risk and protective factors of the South Florida environment, psychostimulant misuse as a risk for meth initiation, and the role of anticipated stigma on stimulant use in SMM. Understanding stimulant use motivations can help to shape intervention development. This includes developing interventions that address individual, interpersonal, and cultural factors that drive stimulant use and increase risk of HIV acquisition. Trial registration NCT04205487.

Abstract Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR‐derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host–microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein‐coupled receptors (GPCRs). NanoLC‐MS/MS analysis and thin‐layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent‐binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics‐aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro‐waste into renewable resources as health‐promoting BPs.

The demand for electric bikes has been increasing in recent years, and so has their drive, which requires a high power-to-weight ratio or a high power density. An axial-flux permanent magnet motor with a Halbach-array is an excellent choice for electric bike drives thanks to its known characteristics of high power density, reliability, and efficiency. However, because an axial-flux machine topology is not common, the manufacturing process can be challenging, especially in the stator core. A good solution to this problem is to remove the stator tooth tips, as this simplifies the stator core shape and makes manufacturing easier. The proposed electric bike has limited housing dimension constraints; thus magnet sensors were implemented to support the Hall sensors in detecting the rotor position. The designed models were analyzed using the 3D finite element method (FEM) to determine their electromagnetic and thermal characteristics. A prototype was manufactured based on the final design and tested under rated conditions to validate the analysis results.

This paper presents a noise reduction technique using common-mode feedback in active CMOS mixers. The proposed technique decreases the common-mode noise, thus reducing the common-to-differential conversion noise arising from mismatch and process variations. In addition, the proposed technique reduces sensitivity to process, voltage, and temperature (PVT) variations due to negative feedback. A negative feedback theory is adopted to analyze the low-noise performance of the proposed technique. The theoretical analysis is validated by simulations and measurements. The conventional and proposed mixers are fabricated in a 65-nm CMOS process. Measurement results of the proposed mixer operating at an RF of 2.1 GHz show a conversion gain of 21.5 dB, the input-referred third-order intercept point (IIP3) of -16.2 dBm, and a flicker noise figure of 8.7 dB at 10 kHz while it dissipates 3.45 mW from a 1.5 V supply voltage. Measurements also show common-mode noise reduction of 10.1 dB at 10 kHz, without degradation of other characteristics. It is demonstrated that the proposed mixer can be applied to decrease phase noise of a self-oscillating mixer (SOM) due to the low common-mode flicker noise mixer.

Automatic analysis of colocalizing biological structures in multi-channel fluorescence microscopy images is an important task to quantify and understand biological processes at high spatial-temporal resolution. Here, we introduce a software suite for colocalization analysis of spot-like objects in multi-channel fluorescence microscopy images. The software suite consists of ColocQuant and ColocJ, and is easy to use for biologists. ColocQuant is a Python-based software with graphical user interface to quantify colocalization of particles in two or three channels. Object-based colocalization is performed by an efficient multi-dimensional graph-based $k$ -d-tree approach, which determines nearest neighbors involved in double or triple colocalization. ColocJ enables efficient and intuitive visualization of the color composition of colocalizations by a Maxwell color triangle and a color ribbon. Colocalization information can be visualized for an entire image or a selected region-of-interest. In addition, global statistics of the particle intensity, particle size, and the number of colocalizations over time are provided. The colocalization analysis results can be exported and used in other software. We illustrate the application of our software suite for multi-channel live cell fluorescence microscopy image sequences of viral proteins in hepatitis C virus infected cells. We performed two-channel and three-channel colocalization analysis.

The Hypenodinae are distributed only in the old world, including the temperate zone of eastern Asia. This study was conducted to review the subfamily Hypenodinae, in which the members have been placed under the different higher taxa. A total of 13 species including one new subspecies under 7 genera of two tribes are recognized from Korea in this study. Among them, one new subspecies, Micreremites pyraloides pyraloides ssp. n., is described as new to science and one species Hypenodes turfosalis Wocke, 1850 was treated to synonymize H. humidalis. Also, all available information, including distribution, images of adults, and genitalic structures, were provided.

In this study, four species of the genus Gracillaria Haworth, 1828 (Lepidoptera: Gracillariidae), are recognized from Korea. Among them, two species, G. albicapitata Issiki, 1930 and G. arsenievi (Ermolaev, 1977), are reported for the first time from Korea. All the known species are enumerated with their available information. Adults and genitalia of all species are redescribed and illustrated.

BackgroundPatients with chronic obstructive pulmonary disease (COPD) have an increased risk of developing lung cancer. Some studies have also suggested that diabetes mellitus (DM) may increase the risk of developing lung cancer. This study aimed to investigate whether type 2 DM (T2DM) is associated with an increased risk of lung cancer in patients with COPD.Materials and methodsWe conducted a retrospective analysis on two cohorts: the National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea and the Common Data Model (CDM) database of a university hospital. Among patients newly diagnosed with COPD in each cohort, those with a lung cancer diagnosis were included, and a control group was selected through propensity score matching. We used the Kaplan–Meier analysis and Cox proportional hazard models to compare lung cancer incidence between patients with COPD and T2DM and those without T2DM.ResultsIn the NHIS-NSC and CDM cohorts, we enrolled 3,474 and 858 patients with COPD, respectively. In both cohorts, T2DM was associated with an increased risk of lung cancer [NHIS-NSC: adjusted hazard ratio (aHR), 1.20; 95% confidence interval (CI), 1.02–1.41; and CDM: aHR, 1.45; 95% CI, 1.02–2.07). Furthermore, in the NHIS-NSC, among patients with COPD and T2DM, the risk of lung cancer was higher in current smokers than in never-smokers (aHR, 1.45; 95% CI, 1.09–1.91); in smokers with ≥30 pack-years than in never-smokers (aHR, 1.82; 95% CI, 1.49–2.25); and in rural residents than in metropolitan residents (aHR, 1.33; 95% CI, 1.06–1.68).ConclusionOur findings suggest that patients with COPD and T2DM may have an increased risk of developing lung cancer compared to those without T2DM.

Background/Aims Germline mutations of the rearranged during transfection (RET) gene cause multiple endocrine neoplasia type 2 (MEN2). About 85% of RET mutations in MEN2 occur in codon Cys634. The RET D631Y mutation has recently been discovered, and we have studied its molecular expression and clinical consequences. Methods We analyzed the clinical characteristics of a total of 34 D631Y variant MEN2 individuals from seven families. We also constructed wild-type and mutant C630Y, D631Y, and C634R/W expression vectors and investigated their effects on signaling pathways and ability to correct the phenotypes of RET mutant cells. Results The median ages at diagnosis of pheochromocytoma and medullary thyroid carcinoma (MTC) were higher in patients with RET D631Y variant MEN2 than in those with the C634R/W variant (49:53.5 years vs. 33.5:27 years, respectively), and the penetration of the D631Y mutation with respect to MTC was lower than that of the C634R/W mutation (32.3% vs. 90%). The effects of the mutant vectors on phosphorylation of RET signaling molecules and focus formation were significantly different from those of wild type, but there were no significant differences between the mutants. D631Y scored significantly higher for chemotaxis and wound healing than C630Y, but lower than C634R and C634W. Conclusions We suggest that the tumorigenic potential conferred by the D631Y mutation is lower than that conferred by the C634R/W mutation, but higher than that conferred by C630Y. Thus, the risk level of the RET D631Y variant appears to be higher than that of C630Y and lower than that of C634R/W.

Neufeldt et al. evaluate transcriptional and cytokine secretion profiles of cells and patient sera following SARS-CoV-2 infection and detect distinct upregulation of inflammatory cytokines. They also demonstrate that this upregulation is mediated by cGAS-STING and NF-κB signalling, which could provide a potential avenue for the development of future therapies against SARS-CoV-2.

Double membrane vesicles (DMV) are used as replication organelles by several RNA viruses. Applying proteomics and lipidomics, Tabata and Prasad et al. find that two cellular acyltransferases (AGPAT1/2), responsible for synthesis of phosphatidic acid, play a role in the DMV-biogenesis of HCV and SARS-CoV-2, highlighting a common biogenesis mechanism for evolutionary distant positive-strand RNA viruses.

Abstract Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

Hepatitis C virus (HCV) is highly diverse and grouped into eight genotypes (gts). Infectious cell culture models are limited to a few subtypes and isolates, hampering the development of prophylactic vaccines. A consensus gt1b genome (termed GLT1) was generated from an HCV infected liver-transplanted patient. GLT1 replicated to an outstanding efficiency in Huh7 cells upon SEC14L2 expression, by use of replication enhancing mutations or with a previously developed inhibitor-based regimen. RNA replication levels almost reached JFH-1, but full-length genomes failed to produce detectable amounts of infectious virus. Long-term passaging led to the adaptation of a genome carrying 21 mutations and concomitant production of high levels of transmissible infectivity (GLT1cc). During the adaptation, GLT1 spread in the culture even in absence of detectable amounts of free virus, likely due to cell-to-cell transmission, which appeared to substantially contribute to spreading of other isolates as well. Mechanistically, genome replication and particle production efficiency were enhanced by adaptation, while cell entry competence of HCV pseudoparticles was not affected. Furthermore, GLT1cc retained the ability to replicate in human liver chimeric mice, which was critically dependent on a mutation in domain 3 of nonstructural protein NS5A. Over the course of infection, only one mutation in the surface glycoprotein E2 consistently reverted to wildtype, facilitating assembly in cell culture but potentially affecting CD81 interaction in vivo. Overall, GLT1cc is an efficient gt1b infectious cell culture model, paving the road to a rationale-based establishment of new infectious HCV isolates and represents an important novel tool for the development of prophylactic HCV vaccines.

Background: Tumor heterogeneity and vascularity can be noninvasively quantified using histogram and perfusion analyses on computed tomography (CT) and magnetic resonance imaging (MRI). We compared the association of histogram and perfusion features with histological prognostic factors and progression-free survival (PFS) in breast cancer patients on low-dose CT and MRI. Methods: This prospective study enrolled 147 women diagnosed with invasive breast cancer who simultaneously underwent contrast-enhanced MRI and CT before treatment. We extracted histogram and perfusion parameters from each tumor on MRI and CT, assessed associations between imaging features and histological biomarkers, and estimated PFS using the Kaplan–Meier analysis. Results: Out of 54 histogram and perfusion parameters, entropy on T2- and postcontrast T1-weighted MRI and postcontrast CT, and perfusion (blood flow) on CT were significantly associated with the status of subtypes, hormone receptors, and human epidermal growth factor receptor 2 (p < 0.05). Patients with high entropy on postcontrast CT showed worse PFS than patients with low entropy (p = 0.053) and high entropy on postcontrast CT negatively affected PFS in the Ki67-positive group (p = 0.046). Conclusions: Low-dose CT histogram and perfusion analysis were comparable to MRI, and the entropy of postcontrast CT could be a feasible parameter to predict PFS in breast cancer patients.

This study aimed to investigate the feasibility of blood-based biomarkers, including blood tumor mutation burden (bTMB), to predict atezolizumab efficacy in relapsed and advanced non-small cell lung cancer (NSCLC). Stage IV NSCLC patients who had previously received platinum-doublet chemotherapy were recruited and received 1200 mg of atezolizumab every three weeks. Blood was collected to obtain plasma cell-free DNA (cfDNA) before the first cycle (C0) and at the fourth cycle (C4). bTMB was measured by CT-ULTRA in patients with cfDNA over 10 ng. The objective response rate (ORR) of the enrolled 100 patients was 10%, and there was no difference in ORR according to bTMB (cutoff: 11.5 muts/Mb) at C0 (high bTMB: 8.1% vs. low bTMB: 11.1%). However, the C4/C0 bTMB ratio was significantly lower in the durable clinical benefit (DCB) patients. The cfDNA concentration at C0, the C4/C0 ratio of the cfDNA concentration, the highest variant allele frequency (hVAF), and the VAF standard deviation (VAFSD) were significantly lower in the DCB patients. In the multivariate analysis, a high cfDNA concentration at C0 (cutoff: 8.6 ng/mL) and a C4/C0 bTMB ratio greater than 1 were significantly associated with progression-free survival. These results suggest that baseline levels and dynamic changes of blood-based biomarkers (bTMB, cfDNA concentration, and VAFSD) could predict atezolizumab efficacy in previously treated NSCLC patients.

Here, we introduce the SMEP (Science Museum Exhibition Platform) system, which is aimed to construct a platform for sharing and exchanging the science museum exhibits and information for museum staff, focusing on natural history collections. The SMEP system currently provides a total of 3030 data of museum exhibits for 11 museums currently, including all the exhibit types of science museum with 6971 images for them. Among them, the natural history collections are a total of 1152 data for eight museums. The loan system of SMEP enables to exchange the collections between museums. A prototype data portal of the SMEP system is operated and will be opened after the further functional review process in later. It is expected that this platform would improve the level of collections in the science museum and create new value by allowing interchange and exchange of collections in science museum.

Oral and gut Bacteroidetes produce unique classes of serine-glycine lipodipeptides and glycine aminolipids that signal through host Toll-like receptor 2. These glycine lipids have also been detected in human arteries, but their effects on atherosclerosis are unknown. Here, we sought to investigate the bioactivity of bacterial glycine lipids in mouse models of atherosclerosis. Lipid 654 (L654), a serine-glycine lipodipeptide species, was first tested in a high-fat diet (HFD)-fed Ldlr−/− model of atherosclerosis. Intraperitoneal administration of L654 over 7 weeks to HFD-fed Ldlr−/− mice resulted in hypocholesterolemic effects and significantly attenuated the progression of atherosclerosis. We found that L654 also reduced liver inflammatory and extracellular matrix gene expression, which may be related to inhibition of macrophage activation as demonstrated in vivo by lower major histocompatibility complex class II gene expression and confirmed in cell experiments. In addition, L654 and other bacterial glycine lipids in feces, liver, and serum were markedly reduced alongside changes in Bacteroidetes relative abundance in HFD-fed mice. Finally, we tested the bioactivities of L654 and related lipid 567 in chow-fed Apoe−/− mice, which displayed much higher fecal glycine lipids relative to HFD-fed Ldlr−/− mice. Administration of L654 or lipid 567 for 7 weeks to these mice reduced the liver injury marker alanine aminotransferase, but other effects seen in Ldlr−/− were not observed. Therefore, we conclude that conditions in which gut microbiome-derived glycine lipids are lost, such as HFD, may exacerbate the development of atherosclerosis and liver injury, whereas correction of such depletion may protect from these disorders.

Salmonella is one of the main foodborne pathogens that affect humans and farm animals. The Salmonella genus comprises a group of food-transmitted pathogens that cause highly prevalent foodborne diseases throughout the world. The aim of this study was to appraise the viability of Salmonella Typhimurium biofilm under water treatment at room temperature on different surfaces, specifically stainless steel (SS), plastic (PLA), rubber (RB), and eggshell (ES). After 35 D, the reduction of biofilm on SS, PLA, RB, and ES was 3.35, 3.57, 3.22, and 2.55 log CFU/coupon without water treatment and 4.31, 4.49, 3.50, and 1.49 log CFU/coupon with water treatment, respectively. The dR value (time required to reduce bacterial biofilm by 99% via Weibull modeling) of S. Typhimurium without and with water treatment was the lowest on PLA (176.86 and 112.17 h, respectively) and the highest on ES (485.37 and 2,436.52 h, respectively). The viability of the S. Typhimurium on ES and the 3 food-contact surfaces was monitored for 5 wk (35 D). The results of this study provide valuable information for the control of S. Typhimurium on different surfaces in the food industry, which could reduce the risk to consumers.

As a member of the class IIa histone deacetylases (HDACs), HDAC9 catalyzes the deacetylation of histones and transcription factors, commonly leading to the suppression of gene transcription. The activity of HDAC9 is regulated transcriptionally and post-translationally. HDAC9 is known to play an essential role in regulating myocyte and adipocyte differentiation and cardiac muscle development. Also, recent studies have suggested that HDAC9 is involved in the pathogenesis of chronic diseases, including cardiovascular diseases, osteoporosis, autoimmune disease, cancer, obesity, insulin resistance, and liver fibrosis. HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases by altering chromatin structure in their promotor region or reducing the transcriptional activity of their respective transcription factors. This review summarizes the current knowledge of the regulation of HDAC9 expression and activity. Also, the roles of HDAC9 in the pathogenesis of chronic diseases are discussed, along with potential underlying mechanisms.

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to the lesional hemisphere requires prudence in selecting the appropriate stimulation spot. Functional near-IR spectroscopy (fNIRS) can be used in both selecting the stimulation spot and assessing the changes of the brain network. This study aimed to evaluate the effect of HF-rTMS on the most activated spot identified with fNIRS and assess the changes of brain functional network in the patients with poststroke aphasia.MethodsA total of five patients received HF-rTMS to the most activated area on the lesional hemisphere, followed by 30 min of speech therapy for 10 days. The Korean version of the Western aphasia battery (K-WAB) and fNIRS evaluation were done 1 day before the treatment, 1 day and 1 month after the last treatment session. Changes of K-WAB and paired cortical interaction and brain network analysis using graph theory were assessed.ResultsAphasia quotient in K-WAB significantly increased after the treatment (P = 0.043). The correlation analysis of cortical interactions showed increased connectivity between language production and processing areas. Clustering coefficients of the left hemisphere were increased over a sparsity range between 0.45 and 0.58 (0.015 < p < 0.031), whereas the clustering coefficients of the right hemisphere, decreased over a sparsity range 0.15–0.87 (0.063 < p < 0.095). The global efficiency became lower over a network sparsity range between 0.47 and 0.75 (0.015 < p < 0.063).ConclusionImprovement of language function and changes of corticocortical interaction between language-related cortical areas were observed after HF-rTMS on the most activated area identified by fNIRS with combined speech therapy in the patients with poststroke aphasia.

Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1–20 μM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 μM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.

We previously reported an anti-fibrogenic effects of fucoxanthin in hepatic stellate cells (HSCs). However, it is unknown whether the primary metabolites of fucoxanthin, such as fucoxanthinol (FCN) and amarouciaxanthin A (ACXA), exert similar functions in fibrogenesis pathways. In this study, we investigated the role of FCN and ACXA in the regulation of transforming growth factor β1 (TGFβ1)-induced pro-fibrogenic gene expression and oxidative stress in LX-2 cells, a human HSC cell line. TGFβ1 increased mRNA expression of pro-fibrogenic genes, such as α smooth muscle actin, procollagen type I α1 (COL1A1), COL3A1, and COL6A1, which FCN and ACXA significantly suppressed. Also, an increase in the protein level of COL1A1 by TGFβ1 was markedly decreased by ACXA. Furthermore, FCN and ACXA significantly inhibited TGFβ1-induced reactive oxygen species (ROS) accumulation with concomitantly decreasing antioxidant gene expression. Mechanistically, FCN and ACXA markedly increased TGFβ1-induced nuclear translocation of nuclear E2-related factor 2 (NRF2); however, they significantly attenuated TGFβ1-induced NFE2L2 and its target gene heme oxygenase-1 expression. The results suggest that FCN and ACXA exert anti-fibrogenic and antioxidant properties by inhibiting TGFβ1-induced pro-fibrogenic gene expression and ROS accumulation in LX-2 cells.

In this study, 29 species of Caloptilia Hübner, 1825, belonging to the family Gracillariidae, were recognized in Korea. Among these, three species, i.e., C. purpureus sp. nov., C. koreana sp. nov., and C. xanthos sp. nov., are described as new to science. In addition, seven species of this genus are reported for the first time in Korea. All known species were enumerated, based on their available information. Adult specimens and genitalia of the new and newly recorded species were examined and described using all available information.

A new lightweight vertical bar plate was developed by inserting individual bars into the plate base rather than the typical sand casting method. The lightweight vertical bar plate has a very sharp bar edge because vertical bars are inserted instead of trapezoidal bars. The refining effects of the mixed stock with softwood bleached kraft pulp (Sw-BKP) and hardwood bleached kraft pulp (Hw-BKP) were compared using two types of lightweight vertical bar plates with cutting edge lengths of 55 km/s (PA55) and 97 km/s (PB97). The fine bar plate (PB97) with large CEL (PB97) was very effective in reducing the refining energy required to reach the final freeness regardless of the mixing ratios of Sw-BKP and Hw-BKP compared to the plate with a small CEL (PA55). PB97 also consumed less refining energy than PA55 until proper sheet strength was achieved. In particular, irrespective of the mixing ratios of Sw-BKP and Hw-BKP, the tensile strength of sheets at the final freeness was greater in PB97 than in PA55. For stock throughput during refining, PA55 with the wide groove was almost similar to PB97 with the narrow groove.

Stress is an organism’s response to a biological or psychological stressor, a method of responding to threats. The autonomic nervous system and hypothalamic–pituitary–adrenal axis (HPA axis) regulate adaptation to acute stress and secrete hormones and excitatory amino acids. This process can induce excessive inflammatory reactions to the central nervous system (CNS) by HPA axis, glutamate, renin-angiotensin system (RAS) etc., under persistent stress conditions, resulting in neuroinflammation. Therefore, in order to treat stress-related neuroinflammation, the improvement effects of several mechanisms of receptor antagonist and pharmacological anti-inflammation treatment were studied. The N-methyl-D-aspartate (NMDA) receptor antagonist, peroxisome proliferator-activated receptor agonist, angiotensin-converting enzyme inhibitor etc., effectively improved neuroinflammation. The interesting fact is that not only can direct anti-inflammation treatment improve neuroinflammation, but so can stress reduction or pharmacological antidepressants. The antidepressant treatments, including selective serotonin reuptake inhibitors (SSRI), also helped improve stress-related neuroinflammation. It presents the direction of future development of stress-related neuroinflammation drugs. Therefore, in this review, the mechanism of stress-related neuroinflammation and pharmacological treatment candidates for it were reviewed. In addition, treatment candidates that have not yet been verified but indicate possibilities were also reviewed.

Studies on natural products that can alleviate the inflammatory response of macrophages caused by endotoxin (lipopolysaccharide) continue. This study investigated the anti-inflammatory activity of baicalin related to macrophage activation caused by lipopolysaccharide (LPS). Baicalin is a flavone glycoside found in plants such as Scutellaria baicalensis and Scutellaria lateriflora belonging to the genus Scutellaria. The multiplex cytokine assay (MCA), Griess reagent assay, fluo-4 calcium assay, dihydrorhodamine 123 (DHR123) assay, quantitative RT-PCR, and flow cytometry were performed using RAW 264.7 mouse macrophages. The MCA revealed that baicalin significantly decreased the production of interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, and RANTES in LPS-stimulated RAW 264.7 macrophages at concentrations of 10, 25, and 50 μM. The DHR123 assay showed that baicalin significantly inhibited reactive oxygen species generation in LPS-stimulated RAW 264.7 macrophages. Flow cytometry revealed that baicalin significantly reduced the levels of phosphorylated p38 MAPK and Fas in LPS-stimulated RAW 264.7 macrophages. Baicalin also inhibited the mRNA expression levels of inflammatory genes such as Chop, Fas, Nos2, Ptgs2, Stat1, c-Jun, c-Fos, and At1a. The IC50 values of baicalin for IL-6, TNF-α, G-CSF, VEGF, interferon gamma-induced protein 10 (IP-10), leukemia inhibitory factor (LIF), lipopolysaccharide-induced CXC chemokine (LIX), MIP-1α, MIP-1β, MIP-2, RANTES, nitric oxide, intracellular calcium, and hydrogen peroxide were 591.3, 450, 1719, 27.68, 369.4, 256.6, 230.7, 856.9, 1326, 1524, 378.1, 26.76, 345.1, and 32.95 μM, respectively. Baicalin modulated the inflammatory response of macrophages activated by LPS via the calcium-CHOP pathway.

Chylomicron metabolism is critical for determining plasma levels of triacylglycerols (TAGs) and cholesterol, both of which are risk factors for CVD. The rates of chylomicron secretion and remnant clearance are controlled by intracellular and extracellular factors, including apoC-III. We have previously shown that human apoC-III overexpression in mice (apoC-IIITg mice) decreases the rate of chylomicron secretion into lymph, as well as the TAG composition in chylomicrons. We now find that this decrease in chylomicron secretion is not due to the intracellular effects of apoC-III, but instead that primary murine enteroids are capable of taking up TAG from TAG-rich lipoproteins (TRLs) on their basolateral surface; and via Seahorse analyses, we find that mitochondrial respiration is induced by basolateral TRLs. Furthermore, TAG uptake into the enterocyte is inhibited when excess apoC-III is present on TRLs. In vivo, we find that dietary TAG is diverted from the cytosolic lipid droplets and driven toward mitochondrial FA oxidation when plasma apoC-III is high (or when basolateral substrates are absent). We propose that this pathway of basolateral lipid substrate transport (BLST) plays a physiologically relevant role in the maintenance of dietary lipid absorption and chylomicron secretion. Further, when apoC-III is in excess, it inhibits BLST and chylomicron secretion.

Phthalate esters (PEs) are the most commonly used plasticizers and one of the endocrine disrupting chemicals (EDCs) which are extensively present in various environment. Therefore, it is important to examine the levels and distribution of phthalates in multimedia environment. This study investigated the seasonal and spatial variation of 14 PEs in air, water, sediments, and fish in the Asan Lake. Asan Lake is one of the largest artificial lakes in Korea, and is surrounded by industrial complex and farmlands. The PEs were found to be present throughout the study area. The mean concentration of total PEs (∑14 PEs) was 3.92–33.09 ng/m3 in air, not detected (n.d.)-2.29 μg/L in water, 3.6–8973 μg/kg dry weight (dw) in sediment, and n.d.-1081 μg/kg dw in fish, respectively. The most frequently detected phthalate in the samples was di(2-ethylhexyl) phthalate (DEHP), and followed by di-n-butyl phthalate (DBP). The concentrations of PEs in water and sediment samples tended to decrease moving downstream of Asan Lake. Bioaccumulation of PEs showed that benthic feeding fish such as crucian carp or skygager contained higher levels of DEHP. Partitioning of DEHP and DBP between water and sediment was calculated using paired sediment/water samples and fugacity fraction (ff). High ff value (ff = 0.89 ± 0.1) of DBP and low ff value of DEHP (ff = 0.24 ± 0.1) confirmed that DEHP is the most abundant PEs in the sediment, and DBP is the second most abundant PEs except DEHP in water. Our results can provide important information of the distribution and behavior of PEs in the lake environment. Keywords: Phthalate esters, DEHP (di(2-ethylhexyl) phthalate), DBP (di-n-butyl phthalate), Sediment-water partitioning, Bioaccumulation, Fugacity fraction

Abstract In this research, we developed electrochemical biosensor which was composed of hemoglobin (Hb)-DNA conjugate on nanoporous gold thin film (NPGF) for hydrogen peroxide (H2O2) detection. For the first time, Hb and DNA was conjugated as a sensing platform for uniform orientation of Hb on electrode. The newly developed Hb-DNA conjugate was designed to prevent Hb from aggregation on electrode. DNA hybridization of Hb-DNA conjugate and complementary DNA (cDNA) on NPGF electrode induced uniformly assembled biosensor. Furthermore, NPGF electrode fabrication method was introduced to the increment of the surface area. To confirm the conjugation of Hb-DNA conjugate, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ultraviolet–visible spectroscopy (UV–VIS) were used. Formation of the NPGF electrode was verified by scanning electron microscope (SEM). Atomic force microscopy (AFM) was operated for the confirmation of Hb-DNA immobilization on electrode. The electrochemical property of fabricated electrode was investigated by cyclic voltammetry (CV). Also, H2O2 sensing performance of fabricated electrode was investigated by amperometric i-t curve technique. This sensor showed a wide linear range from 0.00025 to 5.00 mM and a correlation coefficient of R2 = 0.9986. The detection limit was 250 nM. Proposed biosensor can be utilized as a sensing platform for development of biosensor.