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The skin is the most voluminous organ of the human body and is exposed to the outer environment. Such exposed skin suffers from the effects of various intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, and skin pigmentation. Skin pigmentation occurs in skin aging and is caused by hyper-melanogenesis and oxidative stress. Protocatechuic acid (PCA) is a natural secondary metabolite from a plant-based source widely used as a cosmetic ingredient. We chemically designed and synthesized PCA derivatives conjugated with alkyl esters to develop effective chemicals that have skin-whitening and antioxidant effects and enhance the pharmacological activities of PCA. We identified that melanin biosynthesis in B16 melanoma cells treated with alpha-melanocyte-stimulating hormone (α-MSH) is decreased by PCA derivatives. We also found that PCA derivatives effectively have antioxidant effects in HS68 fibroblast cells. In this study, we suggest that our PCA derivatives are potent ingredients for developing cosmetics with skin-whitening and antioxidant effects.

Iron homeostasis is considered a key factor in human metabolism, and abrogation in the system could create adverse effects, including cancer. Moreover, 6-gingerol is a widely used bioactive phenolic compound with anticancer activity, and studies on its exact mechanisms on non-small cell lung cancer (NSCLC) cells are still undergoing. This study aimed to find the mechanism of cell death induction by 6-gingerol in NSCLC cells. Western blotting, real-time polymerase chain reaction, and flow cytometry were used for molecular signaling studies, and invasion and tumorsphere formation assay were also used with comet assay for cellular processes. Our results show that 6-gingerol inhibited cancer cell proliferation and induced DNA damage response, cell cycle arrest, and apoptosis in NSCLC cells, and cell death induction was found to be the mitochondrial-dependent intrinsic apoptosis pathway. The role of iron homeostasis in the cell death induction of 6-gingerol was also investigated, and iron metabolism played a vital role in the anticancer ability of 6-gingerol by downregulating EGFR/JAK2/STAT5b signaling or upregulating p53 and downregulating PD-L1 expression. Also, 6-gingerol induced miR-34a and miR-200c expression, which may indicate regulation of PD-L1 expression by 6-gingerol. These results suggest that 6-gingerol could be a candidate drug against NSCLC cells and that 6-gingerol could play a vital role in cancer immunotherapy.

Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease in salmonids and rainbow trout fry syndrome. This pathogen has attained a global presence and can spread both horizontally and vertically. However, it was not documented in Korea before September 2018. In this study, the objectives were to characterize Flavobacterium psychrophilum strain FPRT1, isolated from diseased rainbow trout genotypically and phenotypically. We also conducted various investigations to better understand its impact and assess potential control measures. We acquired fifty rainbow trout (approximately 70 g in weight) and transferred them to a laboratory aquarium. During the initial acclimation period, we observed mortality and examined affected fish for clinical signs. We isolated the bacterium from the spleen of infected rainbow trout using tryptone yeast extract salts agar supplemented with glucose, naming this FPRT1. Antibiotic susceptibility testing was carried out, and from the result, we selected enrofloxacin to administer to the trout orally to reduce mortality. To evaluate pathogenicity, we exposed the trout to FPRT1 at different water temperatures (8, 15, and 22 °C). Genomic analysis was conducted to identify the serotype and relatedness of FPRT1 to European strains. Affected fish displayed clinical signs, such as ulcerative lesions in the mandible, anemia with pale gills, exophthalmia, and increased mucus secretion. Internal symptoms included pale liver and enlarged spleen. FPRT1 was susceptible to erythromycin, enrofloxacin, florfenicol, oxytetracycline, and gentamicin, but resistant to oxolinic acid and sulfamethoxazole/trimethoprim. Oral administration of enrofloxacin resulted in a decrease in mortality from 28% to 6%. Pathogenicity tests revealed varying mortality rates due to FPRT1 at different temperatures. The highest rates were observed at 8 °C (ranging from 43% to 100%) for both intraperitoneal and intramuscular injections, and lower rates occurred at 22 °C (ranging from 0% to 30%), with intramuscular injections displaying higher susceptibility. Genomic analysis identified FPRT1 as serotype 2 and indicated its close genetic relationship with European strains based on the core genome and dispensable genome. The substantial genomic similarity between our strain and European strains suggests the possibility of bacterial spread through the importation of fertilized eggs from Europe. In conclusion, this study highlights the introduction of the previously undocumented pathogen (F. psychrophilum) into Korean rainbow trout populations. The detection of this pathogen and its pathogenicity assessment is not only important for understanding its impact on local aquaculture but also for establishing surveillance and control measures to prevent further transmission and outbreaks in the region.

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Global ship analysis is conducted using a finite element model (FE model) for ship design and construction, which involves structural, motion, and vibration analyses. It is crucial to examine the structural safety of the hull and motion response. In the ship FE model used in global ship analysis, weight distribution is employed to adjust the light weight and center of gravity (COG), which are required to perform the analysis. Further, the FE model needs to satisfy the required longitudinal shear force (SF) and bending moment (BM) under the loading conditions of the ship. Moreover, the SF and BM in the ship Trim and Stability data are utilized to perform shear force tuning (SFT) and bending moment tuning (BMT) for the ship FE model. This ensures the ship model exhibits curves of the SF and BM that coincide with those of the ship. The SFT and BMT for the ship FE model are time-consuming and costly. Thus, to address these limitations, we propose an effective and accurate algorithm and program for SFT and BMT. Accordingly, we developed a C#-based algorithm to tune the weight, SF, BM, and COG of the ship FE model to the required target value. Finally, the accuracy of the newly developed algorithm was analyzed and compared by applying it to the shuttle tanker FE model under the ballast and full load conditions. Accuracy was within tolerance in both loading conditions. The average errors of SF and BM were smaller in the ballast condition than in the full load condition, and the errors were smaller at the bow than at the stern.

The toxic element arsenic (As) has become the major focus of global research owing to its harmful effects on human health, resulting in the establishment of several guidelines to prevent As contamination. The widespread industrial use of As has led to its accumulation in the environment, increasing the necessity to develop effective remediation technologies. Among various treatments, such as chemical, physical, and biological treatments, used to remediate As-contaminated environments, biological methods are the most economical and eco-friendly. Microbial oxidation of arsenite (As(III)) to arsenate (As(V)) is a primary detoxification strategy for As remediation as it reduces As toxicity and alters its mobility in the environment. Here, we evaluated the self-detoxification potential of microcosms isolated from Nakdong River water by investigating the autotrophic and heterotrophic oxidation of As(III) to As(V). Experimental data revealed that As(III) was oxidized to As(V) during the autotrophic and heterotrophic growth of river water microcosms. However, the rate of oxidation was significantly higher under heterotrophic conditions because of the higher cell growth and density in an organic-matter-rich environment compared to that under autotrophic conditions without the addition of external organic matter. At an As(III) concentration > 5 mM, autotrophic As(III) oxidation remained incomplete, even after an extended incubation time. This inhibition can be attributed to the toxic effect of the high contaminant concentration on bacterial growth and the acidification of the growth medium with the oxidation of As(III) to As(V). Furthermore, we isolated representative pure cultures from both heterotrophic- and autotrophic-enriched cultures. The new isolates revealed new members of As(III)-oxidizing bacteria in the diversified bacterial community. This study highlights the natural process of As attenuation within river systems, showing that microcosms in river water can detoxify As under both organic-matter-rich and -deficient conditions. Additionally, we isolated the bacterial strains HTAs10 and ATAs5 from the microcosm which can be further investigated for potential use in As remediation systems. Our findings provide insights into the microbial ecology of As(III) oxidation in river ecosystems and provide a foundation for further investigations into the application of these bacteria for bioremediation.

With the rapid growth of aging populations in South Korea, it is important to assess spatial accessibility to healthcare resources as older adults may need frequent visits to hospitals. Healthcare spatial accessibility is measured based on available resources (e.g., physicians, beds, services), demands (e.g., population), and travel costs (e.g., distance or time). In this study, we employed an Enhanced Two-Step Floating Catchment Area (E2SFCA) method to measure the spatial accessibility to primary care for older populations (i.e., aged 65 and older) in major cities in South Korea, including Seoul, Busan, Daegu, Incheon, Gwangju, Daejeon, and Ulsan. We found that the aging population in Seoul, the capital and biggest city in South Korea, has relatively better accessibility than those living in other cities. We also discovered a negative relationship between accessibility to primary care and the aging index (i.e., population over 65 years old/population less than 15 years old); the regions with a higher ratio of older populations have lower accessibility to primary care. The results suggested that more primary care services (perhaps via mobile vans) are needed in regions predominantly with older people to improve their healthcare access.

Overall, 836 Escherichia coli isolates (695 isolates from dogs and 141 from cats) were recovered from the diarrhea, skin/ear, urine, and genitals of dogs and cats between 2018 and 2019. Cefovecin and enrofloxacin resistance were noted in 17.1% and 21.2% of E. coli isolates, respectively. The cefovecin and enrofloxacin resistance rates were higher in dog isolates (18.1% and 22.9%) compared with the rates in cat isolates (12.1%, 12.8%). Interestingly, resistance to both antimicrobials was noted in 10.8% (90/836) of the isolates, predominantly in isolates from dogs. blaCTX-M-14, blaCTX-M-15, and blaCMY-2 were the most frequent extended-spectrum β-lactamase/plasmid-mediated AmpC β-lactamase (ESBL/AmpC)- gene types. The co-existence of blaCTX-M andblaCMY-2 was noted in six E. coli isolates from dogs. Sequencing analysis demonstrated that S83L and D87N in gyrA and S80I in parC were the most frequent point mutations in the quinolone resistance-determining regions of the cefovecin and enrofloxacin-resistant isolates. A total of 11 isolates from dogs carried the plasmid-mediated quinolone resistance genes (six aac(6’)-Ib-cr, four qnrS, and one qnrB), while only two cat isolates carried the qnrS gene. Multilocus sequence typing of the cefovecin and enrofloxacin-resistant isolates revealed that sequence type (ST)131 E. coli carrying blaCTX-M-14 and blaCTX-M-15 genes and ST405 E. coli carrying blaCMY-2 gene were predominant among the isolated E. coli strains. The majority of the ESBL/AmpC-producing isolates displayed diverse pulsed-field gel electrophoresis profiles. This study demonstrated that third-generation cephalosporin- and fluoroquinolone-resistant E. coli were widely distributed in companion animals. The detection of the pandemic ST131 clone carrying blaCTX-M-14/15 in companion animals presented a public health threat.

Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers patients’ quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients’ quality of life. Further research will help understand the mechanisms and develop new strategies in the future.

The primary purpose of this study is to develop a method that can assist in exploring infrastructure-related multidimensional data. The spatial distribution of social infrastructure, including housing and service facilities, is usually uneven across a nation. The underlying reasons behind the spatial configuration of infrastructure vary, and its comprehensive examination is crucial to understanding the true implications of their skewed distribution. However, simultaneous examination of all social infrastructure is not always straightforward due to the volume of data. The presence of strong correlations between the facilities may further impede the finding of meaningful patterns. To this end, we present an extension of PCA that constructs sparse principal components for local subsets of the data. To demonstrate its strengths and limitations, we apply it to a dataset on housing and service facilities in Korea. The results exhibit clear geographic patterns and offer valuable insights into the spatial patterns of social infrastructure, which the standard PCA only partly addressed. It provides empirical evidence that the proposed method can be an effective alternative to the traditional dimension reduction techniques for exploring spatial heterogeneity in massive multidimensional data.

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to ‘hematological system development and function’ and ‘hematological disease.’ Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract.

To understand the microphysical characteristics of rainfall in four different climatological regions (called BOS, BUS, CPO, and JIN) in South Korea, DSDs and their variables, including the mass-weighted mean diameter (Dm) and normalized number concentration (logNw), were examined. To examine the characteristics of DSDs at four sites with different climatology and topography, data measured from Parsivel disdrometer and wind direction from Automatic Weather System (AWS) during rainy seasons from June to August for three years (2018 to 2020) were analyzed. The DSDs variables were calculated using Gamma distribution model. In the coastal area, larger raindrops with a lower number concentration occurred, whereas smaller raindrops with a higher number concentration dominated in the middle land and mountain region. The mountain area of CPO and middle land area of JIN had a larger contribution to the rain rate than that of the coastal area of BOS and JIN in the range of the smallest diameter. The contribution of the drop size to the total number concentration at the CPO and JIN sites was larger (smaller) than that at BOS and BUS in the smallest (larger) diameter. The average shape and slope parameter of gamma model were higher values at the mountain area than at other sites for both rain types, Z-R relation and polarimetric variables were also shown different values at the four studied sites. The intercept coefficient of Z-R relation showed higher values in the mountain area and middle land area than the coastal area. The slope values of Z-R relation were the smallest in the mountain area. The polarimetric variables of ZH and ZDR were shown highest (lowest) value at the coastal region of BOS (mountain area of CPO) site for both rain types. The Dm-rose, which shows the Dm distributions with the wind direction, was used in this study. In the coastal area (mountain and middle land area), the dominant wind was east–southeast (east) direction. The ratio of the smaller diameter to the middle size at BOS was much smaller than that at CPO. In the analysis of the hourly distribution of the Dm and logNw, there were two and four peaks of Dm at BUS and BOS, respectively. There was one peak of the Dm at the CPO and JIN sites. The time variation of the Dm was much higher than that of the logNw.

Fibroblast growth factor receptor-2 (FGFR2) gene alterations have been identified in solid tumors. FGFR2 amplification is found in 2–9% of gastric carcinomas. We hypothesized that FGFR2 could be associated with peritoneal seeding and studied 360 advanced gastric carcinoma patients; 222 (61.7%) were male, 246 (73.7%) had poorly differentiated histology, and 175 (48.6%) presented with peritoneal seeding. High tumor mutation burden (TMB) was observed in 44 (12.2%) patients, high microsatellite instability (MSI) was observed in 12 (3.33%) patients, ERBB2 amplification was observed in 44 (12.2%) patients, EBV positivity was observed in 10 (10/278; 3.6%) patients, and PD-L1 positivity was observed in 186 (186/264; 70.5%) cases. We found FGFR2 amplification in 26 (7.2%) patients, of which 12 (46.2%) were female and 22 (84.6%) had poorly differentiated histology. In these 26 cases, the copy number of FGFR2 amplification ranged from 3.7 to 274. Eighteen of them showed seeding, and this association was statistically significant (18/26, 69.2%; 157/334, 47%; p = 0.023). In addition, high TMB was significantly associated with seeding (p = 0.028; OR = 1.83). Poorly differentiated histology was significantly associated with seeding (p = 0.04) but not with FGFR2 amplification (p > 0.1). Seeding was frequent in gastric carcinoma patients with FGFR2 amplification, in patients with high TMB, or in those who were female. The subgroup of patients with FGFR2 amplification could be potential candidates for targeted therapeutic agents.

Detecting microsatellite instability (MSI) in advanced cancers is crucial for clinical decision-making, as it helps in identifying patients with differential treatment responses and prognoses. BAT26 is a highly sensitive MSI marker that defines the mismatch repair (MMR) status with high sensitivity and specificity. However, isolated BAT26-only instability is rare and has not been previously reported. Of the 6476 cases tested using pentaplex MSI polymerase chain reaction, we identified two BAT26-only instability cases (0.03%) in this study. The case #1 patient was diagnosed with endometrial adenocarcinoma without MMR germline mutations. The endometrial tumor showed BAT26-only instability, partial loss of MLH1/PMS2 protein expression, and a high programmed cell death ligand 1 (PD-L1) combined positive score (CPS = 8). The tumor exhibited a somatic phosphatase and tensin homolog (PTEN) R303P missense mutation and loss of the PTEN protein. On a comprehensive cancer panel sequencing with ≥500 genes, the tumor showed an MSI score of 11.38% and high tumor mutation burden (TMB) (19.5 mt/mb). The case #2 patient was diagnosed with colorectal carcinoma with proficient MMR and PTEN protein loss without PTEN alteration, as well as a high PD-L1 CPS (CPS = 10). A pathogenic KRAS A146T mutation was detected with an MSI score of 3.36% and high TMB (13 mt/mb). In conclusion, BAT26-only instability is very rare and associated with PTEN protein loss, high TMB, and a high PD-L1 score. Our results suggest that patients with BAT26-only instability may show good responses to immunotherapy.

Inertial sensors are widely used for classifying the motions of daily activities. Although hierarchical classification algorithms were commonly used for defined motions, deep-learning models have been used recently to classify a greater diversity of motions. In addition, ongoing studies are actively investigating algorithm efficiency (e.g., training time and accuracy). Thus, a deep-learning model was constructed in this study for the classification of a given motion based on the raw data of inertial sensors. Furthermore, the number of epochs (150, 300, 500, 750, and 900) and hidden units (100, 150, and 200) were varied in the model to determine its efficiency based on training time and accuracy, and the optimum accuracy and training time was determined. Using a basic long short-term memory (LSTM), which is a neural network known to be suitable for sequential data, the data classification training was conducted on a common desktop PC with typical specifications. The results show that the accuracy was the highest (99.82%) with 150 hidden units and 300 epochs, while the training time was also relatively short (78.15 min). In addition, the model accuracy did not always increase even when the model complexity was increased (by increasing the number of epochs and hidden units) and the training time increased as a consequence. Hence, through suitable combinations of the two factors that constitute deep-learning models according to the data, the potential development and use of efficient models have been verified. From the perspective of training optimization, this study is significant in having determined the importance of the conditions for hidden units and epochs that are suitable for the given data and the adverse effects of overtraining.

Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often present on the scalp, forehead, chest, back, upper arms, elbows, groin, and behind the ears, predominantly in seborrheic areas. A 48-year-old male patient presented skin lesions with pruritus on the trunk and both upper and lower extremities. He first noticed the lesion 15 years before. On physical examination, there were multiple erythematous papules with crust on the trunk and red-brown colored keratotic plaque on both extremities. The suspected histopathological diagnosis was psoriasis vulgaris. The patient’s skin lesions and pruritus were significantly improved after the psoriasis treatment. While continuing psoriasis treatment, the patient showed sudden worsening of the skin lesions on the scalp, abdomen, and fingernails (V-shaped nicks) with pruritus. Punch biopsy was performed on the abdominal lesion again and the final diagnosis was Darier disease. The patient was then treated using alitretinoin while maintaining the use of guselkumab for psoriasis. There are only a few cases that we found in which patients with Darier disease also had psoriasis. We report this rare case of Darier disease with psoriasis and propose that an additional biopsy might be necessary for accurate diagnosis and proper treatment.

As interest in skin increases, the cosmetic market is also growing. It is difficult to choose between the numerous types of basic cosmetics on the market. This article aims to provide advice and guidance on which products to recommend according to a patient’s skin condition. Appropriate application of a moisturizer attempts not only to improve the dryness, but also improve the skin’s natural barrier function to protect the skin from internal and external irritants to keep the skin healthy. Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants, lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to provide readers with the background they need to choose the right moisturizer for themselves. As moisturizers play an important role as adjuvant in the treatment of common skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be recommended in consideration of the ingredients, effectiveness and safety of each product, and the skin condition of each patient.

18F-florbetaben (FBB) positron emission tomography is a representative imaging test that observes amyloid deposition in the brain. Compared to delay-phase FBB (dFBB), early-phase FBB shows patterns related to glucose metabolism in 18F-fluorodeoxyglucose perfusion images. The purpose of this study is to prove that classification accuracy is higher when using dual-phase FBB (dual FBB) versus dFBB quantitative analysis by using machine learning and to find an optimal machine learning model suitable for dual FBB quantitative analysis data. The key features of our method are (1) a feature ranking method for each phase of FBB with a cross-validated F1 score and (2) a quantitative diagnostic model based on machine learning methods. We compared four classification models: support vector machine, naïve Bayes, logistic regression, and random forest (RF). In composite standardized uptake value ratio, RF achieved the best performance (F1: 78.06%) with dual FBB, which was 4.83% higher than the result with dFBB. In conclusion, regardless of the two quantitative analysis methods, using the dual FBB has a higher classification accuracy than using the dFBB. The RF model is the machine learning model that best classifies a dual FBB. The regions that have the greatest influence on the classification of dual FBB are the frontal and temporal lobes.

Oil-contaminated soil is a major societal problem for humans and the environment. In this study, the pyrolysis method was applied to oil-contaminated soil used as a landfill and gas station site in Korea. The removal efficiency of the main components of oil-contaminated soils, such as total petroleum hydrocarbons (TPH), polyaromatic hydrocarbons (PAHs), unresolved complex mixture (UCM), and alkylated PAHs (Alk-PAHs) were measured, and the effect of temperature, treatment time, and moisture content on pyrolysis efficiency was studied. In order to evaluate the risk of soil from which pollutants were removed through pyrolysis, integrated ecotoxicity was evaluated using Daphnia magna and Allivibrio fischeri. The chemical and biological measurements in this study include contaminants of emerging concerns (CECs). Results showed that the pyrolysis was more efficient with higher treatment temperatures, moisture content, and treatment times. In addition, toxicity was reduced by 99% after pyrolysis, and the degree of toxicity was evaluated more sensitively in Allivibrio fischeri than in Daphnia magna. This study shows that weathered oil-contaminated soil can be effectively treated in a relatively short time through pyrolysis, as well as provides information on efficient conditions and the assessment of ecotoxicity.

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, is important for xenobiotic metabolism and binds to various endogenous and exogenous ligands present in the skin. AhR is known to be associated with diseases in various organs; however, its functions in chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis (PS), have recently been elucidated. Here, we discuss the molecular mechanisms of AhR related to chronic inflammatory skin diseases, such as AD and PS, and the mechanisms of action of AhR on the skin immune system. The importance of AhR molecular biological pathways, clinical features in animal models, and AhR ligands in skin diseases need to be investigated. In conclusion, the therapeutic effects of AhR ligands are demonstrated based on the relationship between AhR and skin diseases. Nevertheless, further studies are required to elucidate the detailed roles of AhR in chronic inflammatory skin diseases.

Gastric cancer (GC) remains one of the most common deadly malignancies worldwide. Recently, several targeted therapeutics for treating unresectable or metastatic GC have been developed. Comprehensive characterization of the molecular profile and of the tumor immune microenvironment of GC has allowed researchers to explore promising biomarkers for GC treatment and has enabled a new paradigm in precision-targeted immunotherapy. In this article, we review established and promising new biomarkers relevant in GC, with a focus on their clinical implications, diagnostic methods, and the efficacy of targeted agents.

Antimicrobial-resistant bacteria in food animals pose a major public health threat worldwide. In this study, we aimed to assess the antimicrobial resistance profiles and resistance trends of commensal Escherichia coli isolated from the feces of healthy cattle, pigs, and chickens in South Korea during 2010 and 2020. A total of 7237 E. coli isolates (2733 cattle, 2542 pig, and 1962 chicken isolates) were tested for susceptibility towards 12 antimicrobials. About 48%, 90%, and 97% of cattle, pig, and chicken isolates, respectively, were resistant to one or more antimicrobial agents. Cattle isolates presented low resistance (45%) resistance rate to ampicillin, chloramphenicol, streptomycin, and tetracycline. We observed high ciprofloxacin and nalidixic acid resistance rates in chicken (76.1% and 88.6%, respectively), isolates in pig (12.7% and 26.7%, respectively) and cattle (2.7% and 8.2%, respectively) isolates. Notably, a very small proportion of isolates (E. coli isolated from major food animals in Korea to commonly used antimicrobials including critically important antimicrobials. These bacteria could not only be a resistance reservoir but also could have potential to spread this resistance through gene transfer to pathogenic bacteria. Thus, the high prevalence of antimicrobial resistance in food animals highlights the urgent need for measures to restrict and ensure the prudent use of antimicrobials in Korea.

Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overexpression of CUG2 on microRNA levels using a microRNA microarray. Levels of miR-3656 were decreased when CUG2 was overexpressed; on the basis of this result, we further examined the target proteins of this microRNA. We focused on Jumonji C domain-containing protein 5 (JMJD5), as it has not been previously reported to be targeted by miR-3656. When CUG2 was overexpressed, JMJD5 expression was upregulated compared to that in control cells. A 3′ untranslated region (UTR) assay revealed that an miR-3656 mimic targeted the JMJD5 3′UTR, but the miR-3656 mimic failed to target a mutant JMJD5 3′UTR, indicating that miR-3656 targets the JMJD5 transcript. Administration of the miR-3656 mimic decreased the protein levels of JMD5 according to Western blotting. Additionally, the miR-3656 mimic decreased CUG2-induced cell migration, evasion, and sphere formation and sensitized the cells to doxorubicin. Suppression of JMJD5, with its small interfering RNA, impeded CUG2-induced cancer stem cell-like phenotypes. Thus, overexpression of CUG2 decreases miR-3656 levels, leading to upregulation of JMJD5, eventually contributing to cancer stem cell-like phenotypes.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95–500 μg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part’s antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box–Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case–control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20–0.57; enterolactone, OR = 0.32, 95%CI 0.18–0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26–0.96; OR = 0.38, 95%CI 0.19–0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22–0.81; OR = 0.28, 95%CI 0.14–0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Silicon is an attractive anode material for lithium-ion batteries (LIBs) because of its natural abundance and excellent theoretical energy density. However, Si-based electrodes are difficult to commercialize because of their significant volume changes during lithiation that can result in mechanical damage. To overcome this limitation, we synthesized an eco-friendly water-soluble polyimide (W-PI) precursor, poly(amic acid) salt (W-PAmAS), as a binder for Si anodes via a simple one-step process using water as a solvent. Using the W-PAmAS binder, a composite Si electrode was achieved by low-temperature processing at 150 °C. The adhesion between the electrode components was further enhanced by introducing 3,5-diaminobenzoic acid, which contains free carboxylic acid (–COOH) groups in the W-PAmAS backbone. The –COOH of the W-PI binder chemically interacts with the surface of Si nanoparticles (SiNPs) by forming ester bonds, which efficiently bond the SiNPs, even during severe volume changes. The Si anode with W-PI binder showed improved electrochemical performance with a high capacity of 2061 mAh g−1 and excellent cyclability of 1883 mAh g−1 after 200 cycles at 1200 mA g−1. Therefore, W-PI can be used as a highly effective polymeric binder in Si-based high-capacity LIBs.

Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSC using natural compounds is a good approach as it suppresses cancer recurrence with fewer adverse effects, and methylsulfonylmethane (MSM) is a sulfur-containing compound with well-known anticancer activities. This study determined the mechanistic aspects of the anticancer activity of MSM. We used Western blotting and real-time qPCR for molecular signaling studies and conducted flow cytometry for analyzing the processes in cells. Our results suggested an inhibition in the expression of CSC markers and Wnt/β-catenin signaling. MSM induced TRAIL-mediated extrinsic apoptosis in NCCIT and NTERA-2 cells rather than an intrinsic pathway. Inhibition of iron metabolism-dependent reactive oxygen species (ROS) generation takes part in TRAIL-mediated apoptosis induction by MSM. Suppressing iron metabolism by MSM also regulated p38/p53/ERK signaling and microRNA expressions, such as upregulating miR-130a and downregulating miR-221 and miR-222, which resulted in TRAIL induction and thereby extrinsic pathway of apoptosis. Hence, MSM could be a good candidate for neoadjuvant therapy by targeting CSCs by inhibiting iron metabolism.

We investigated the association between dietary habits, evaluated using the modified Mini Dietary Assessment Index for Koreans (MDA), and lipid control among patients aged ≥20 years who had used pravastatin for dyslipidemia for 6 months. Participants were administered questionnaires regarding sociodemographic characteristics and lifestyle factors. Odds ratios and 95% confidence intervals for the control of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at 6 months for each category of the modified MDA items were calculated through multivariate logistic regression analysis. The odds for controlled LDL-C was higher among those who consumed cholesterol-rich foods

(1) Background: The stochastic nature of agent-based models (ABMs) may be responsible for the variability of simulated outputs. Multiple simulation runs (i.e., replicates) need to be performed to have enough sample size for hypothesis testing and validating simulations. The simulation outputs in the early-stage of simulations from non-terminating ABMs may be underestimated (or overestimated). To avoid this initialization bias, the simulations need to be run for a burn-in period. This study proposes to use multiple scale space-time patterns to determine the number of required replicates and burn-in periods in spatially explicit ABMs, and develop an indicator for these purposes. (2) Methods: ABMs of vector-borne disease transmission were used as the case study. Particularly, we developed an index, D, which enables to take into consideration a successive coefficient of variance (CV) over replicates and simulation years. The comparison between the number of replicates and the burn-in periods determined by D and those chosen by CV was performed. (3) Results: When only a single pattern was used to determine the number of replicates and the burn-in periods, the results varied depending on the pattern. (4) Conclusions: As multiple scale space-time patterns were used for the purposes, the simulated outputs after the burn-in periods with a proper number of replicates would well reproduce multiple patterns of phenomena. The outputs may also be more useful for hypothesis testing and validation.

Tumor immune escape is a common process in the tumorigenesis of non-small cell lung cancer (NSCLC) cells where programmed death ligand-1 (PD-L1) expression, playing a vital role in immunosuppression activity. Additionally, epidermal growth factor receptor (EGFR) phosphorylation activates Janus kinase-2 (JAK2) and signal transduction, thus activating transcription 3 (STAT3) to results in the regulation of PD-L1 expression. Chemotherapy with commercially available drugs against NSCLC has struggled in the prospect of adverse effects. Nobiletin is a natural flavonoid isolated from the citrus peel that exhibits anti-cancer activity. Here, we demonstrated the role of nobiletin in evasion of immunosuppression in NSCLC cells by Western blotting and real-time polymerase chain reaction methods for molecular signaling analysis supported by gene silencing and specific inhibitors. From the results, we found that nobiletin inhibited PD-L1 expression through EGFR/JAK2/STAT3 signaling. We also demonstrated that nobiletin exhibited p53-independent PD-L1 suppression, and that miR-197 regulates the expression of STAT3 and PD-L1, thereby enhancing anti-tumor immunity. Further, we evaluated the combination ability of nobiletin with an anti-PD-1 monoclonal antibody in NSCLC co-culture with peripheral blood mononuclear cells. Similarly, we found that nobiletin assisted the induction of PD-1/PD-L1 blockade, which is a key factor for the immune escape mechanism. Altogether, we propose nobiletin as a modulator of tumor microenvironment for cancer immunotherapy.

Treatment of infectious diseases caused by carbapenem-resistant Pseudomonas aeruginosa is becoming a greater challenge. This study aimed to identify the imipenem resistance mechanism in P. aeruginosa isolated from a dog. Minimum Inhibitory Concentration (MIC) was determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute recommendations. We performed polymerase chain reaction and whole-genome sequencing to detect carbapenem resistance genes. Genomic DNA of P. aeruginosa K19PSE24 was sequenced via the combined analysis of 20-kb PacBio SMRTbell and PacBio RS II. Peptide-Peptide Nucleic Acid conjugates (P-PNAs) targeting the translation initiation region of blaOXA-913 were synthesized. The isolate (K19PSE24) was resistant to imipenem and piperacillin/tazobactam yet was susceptible to most of the tested antimicrobials. Whole-genome sequencing revealed that the K19PSE24 genome comprised a single contig amounting to 6,815,777 base pairs, with 65 tRNA and 12 rRNA genes. K19PSE24 belonged to sequence type 313 and carried the genes aph(3)-IIb, fosA, catB7, crpP, and blaOXA-913 (an allele deposited in GenBank but not described in the literature). K19PSE24 also carried genes encoding for virulence factors (exoenzyme T, exotoxin A, and elastase B) that are associated with adhesion, invasion, and tissue lysis. Nevertheless, we did not detect any of the previously reported carbapenem resistance genes. This is the first report of the blaOXA-913 gene in imipenem-resistant P. aeruginosa in the literature. Notably, no viable colonies were found after co-treatment with imipenem (2 µg/mL) and either of the P-PNAs (12.5 µM or 25 µM). The imipenem resistance in K19PSE24 was primarily due to blaOXA-913 gene carriage.

Iron metabolism and heme biosynthesis are essential processes in cells during the energy cycle. Alteration in these processes could create an inflammatory condition, which results in tumorigenesis. Studies are conducted on the exact role of iron/heme metabolism in induced inflammatory conditions. This study used lipopolysaccharide (LPS)- or high-glucose-induced inflammation conditions in THP-1 cells to study how iron/heme metabolism participates in inflammatory responses. Here, we used iron and heme assays for measuring total iron and heme. We also used flow cytometry and Western blotting to analyze molecular responses. Our results demonstrated that adding LPS or high-glucose induced iron formation and heme synthesis and elevated the expression levels of proteins responsible for iron metabolism and heme synthesis. We then found that further addition of heme or 5-aminolevulinic acid (ALA) increased heme biosynthesis and promoted inflammatory responses by upregulating TLR4/NF-κB and inflammatory cytokine expressions. We also demonstrated the inhibition of heme synthesis using succinylacetone (SA). Moreover, N-MMP inhibited LPS- or high-glucose-induced inflammatory responses by inhibiting TLR4/NF-κB signaling. Hence, iron/heme metabolism checkpoints could be considered a target for treating inflammatory conditions.

Sulfur is an essential nutrient—along with nitrogen, phosphorus, and potassium—for plant growth and development. Sulfur is mostly supplied to crops through soil fertilizers. However, chemical fertilizers are overused to increase crop yields despite environmental threats. The proper use of chemical fertilizers positively affects crop growth and yield increase. Regardless, residues from misuse threaten not only the soil ecosystem, but also the marine ecosystem. Therefore, the need to minimize chemical fertilizer abuse is imperative. This article reports that sulfur can be applied to crop leaves as nontoxic sulfur (NTS) in trace amounts to positively affect plant hormones, chloroplast content, and ROS scavenging system, thereby promoting growth, and increasing crop yields. Furthermore, NTS and microelements, the micronutrients calcium and magnesium, produced a synergistic effect when applied together, and NTS enhanced the expression of auxin and gibberellin-related genes. Additionally, chlorophyll content was increased, and ROS scavenging ability was greatly improved. Therefore, NTS can effectively deliver potent growth-promoting functions of plants faster and safer than did soil fertilizers and consequently increase crop yield. This finding is a new strategy to replace soil chemical fertilizers in supplying sulfur. It is potentially valuable for increasing crop yields and can be applied to other crops.

Psoriasis is a chronic inflammatory systemic disease primarily affecting the skin, but which often involves considerable comorbidities as well. One-third of psoriasis cases start during childhood. In pediatric psoriasis, an association with several medical comorbidities is also indicated. Furthermore, because of its chronic nature and frequent relapses, psoriatic patients tend to require long-term treatment and experience negative impacts on their quality of life. Considering the different clinical characteristics of pediatric psoriasis, it has recently been presented that the pathogenesis of pediatric psoriasis is distinct from adult psoriasis. Treatment for pediatric psoriasis usually involves the same methods as for adults. However, most treatments in pediatric psoriasis are used off-label and research in this regard is still lacking. Targeted therapies involving newly developed biologics are also increasingly being applied to psoriasis in children. This review summarizes the clinical characteristics of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and treatments in pediatric psoriasis. This was undertaken to widen the understanding of these relevant aspects and to provide better management of pediatric psoriasis by clinicians.

Along with the fourth industrial revolution, research in the biomedical engineering field is being actively conducted. Among these research fields, the brain–computer interface (BCI) research, which studies the direct interaction between the brain and external devices, is in the spotlight. However, in the case of electroencephalograph (EEG) data measured through BCI, there are a huge number of features, which can lead to many difficulties in analysis because of complex relationships between features. For this reason, research on BCIs using EEG data is often insufficient. Therefore, in this study, we develop the methodology for selecting features for a specific type of BCI that predicts whether a person correctly detects facial expression changes or not by classifying EEG-based features. We also investigate whether specific EEG features affect expression change detection. Various feature selection methods were used to check the influence of each feature on expression change detection, and the best combination was selected using several machine learning classification techniques. As a best result of the classification accuracy, 71% of accuracy was obtained with XGBoost using 52 features. EEG topography was confirmed using the selected major features, showing that the detection of changes in facial expression largely engages brain activity in the frontal regions.

Menopause is a matter of concern for women’s health due to a deficiency of female hormones; additionally, reactive oxygen species and aging can cause osteoporosis. Food becomes increasingly interesting as a menopausal woman’s alternative to hormone therapy. The effects of ethanol extracts from dark purple Superjami rice bran on bone metabolism and antioxidant defense systems in menopause-induced animal models were evaluated. Female rats underwent sham surgery or were ovariectomized to induce a menopause-like state. Rats were divided into a sham control group (SHAM), an ovariectomized control group (OVX), and an ovariectomized grou supplemented with Superjami rice bran extract group (OVX-S) and fed for 8 weeks. The OVX groups exhibited significantly more weight gain, amounts of bone turnover biochemical markers (alkaline phosphatase, osteocalcin, and C-terminal telopeptide), bone loss, lipid-peroxidation and oxidative stress than the SHAM group. However, Superjami bran extract added to the diet resulted in a significant reduction in body weight and lipid peroxidation, as well as enhanced bone metabolism and antioxidant enzyme activities, in ovariectomized rats. These results propound that extracts from Superjami rice bran have therapeutic potentiality against bone loss and oxidative stress in menopause-induced states and will be useful in preventing postmenopausal osteoporosis and oxidative damage.

The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are poorly understood. In this study, RNA sequencing (RNA-seq) data showed that the expression levels of metallothionein-1 (MT1) isoforms, including MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X, were increased in human pulmonary alveolar epithelial cells (HPAEpiCs) that were treated with PHMG but not in those treated with CMIT. Moreover, upregulation of MT1B, MT1F, MT1G, and MT1H was observed only in PHMG-treated HPAEpiCs. The protein expression level of metal regulatory transcription factor 1 (MTF1), which binds to the promoters of MT1 isoforms, was increased in PHMG-treated HPAEpiCs but not in CMIT-treated HPAEpiCs. However, the expression of early growth response 1 (EGR1) and nuclear receptor superfamily 3, group C, member 1 (NR3C1), other transcriptional regulators involved in MT1 isomers, were increased regardless of treatment with PHMG or CMIT. These results suggest that MTF1 is an essential transcription factor for the induction of MT1B, MT1F, MT1G, and MT1H by PHMG but not by CMIT.

The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands.

Itching is prevalent in children with skin disorders and associated with effects on their mood, quality of life, and social functioning. Surprisingly, there are no data on childhood prevalence of pruritus in the general population. The aim of this article is to explore the epidemiology, clinical manifestation, and treatment for itch (pruritus) in the pediatric population (from infancy to adolescence), and to be helpful to primary care physicians who assess and diagnose pediatric patients with itching. In this study, we searched for specific keywords using PubMed and MEDLINE (Ovid) and, then, refined the retrieved searches for each cause and treatment. As a result of reviewing the literature, atopic dermatitis was shown to be the most common cause of itching, especially during infancy and through preschool. Not only skin disorders but also systemic diseases, drugs, and postburn states can predispose an individual to itching in childhood. There are traditional and newly developed treatment modalities for itching in pediatric patients. However, because the pharmacokinetics and pharmacodynamics of childhood are different from those of adults, the medications for itching have to be applied carefully for these age groups. There are many areas to be elucidated regarding the prevalence and objective assessment of pruritus in pediatric patients. Moreover, the safety profiles of medications in the pediatric population need to be better understood. Further studies to investigate itching in childhood are warranted.

The purpose of this study is to investigate the effect of the fabrication method of dental prosthesis on the mechanical properties. Casting was produced using the lost wax casting method, and milling was designed using a CAD/CAM program. The 3D printing method used the SLS technique to create a three-dimensional structure by sintering metal powder with a laser. When making the specimen, the specimen was oriented at 0, 30, 60, and 90 degrees. All test specimens complied with the requirements of the international standard ISO 22674 for dental alloys. Tensile strength was measured for yield strength, modulus of elasticity and elongation by applying a load until fracture of the specimen at a crosshead speed of 1.5 ± 0.5 mm/min (n = 6, modulus of elasticity n = 3). After the tensile test, the cross section of the fractured specimen was observed with a scanning electron microscope, and the statistics of the data were analyzed with a statistical program SPSS (IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY, USA: IBM Corp.) and using Anova and multiple comparison post-tests (scheffe method). The yield strength was the highest at 1042 MPa at an angle of 0 degrees in the specimen produced by 3D printing method, and the elongation was the highest at 14% at an angle of 90 degrees in the specimen produced by 3D printing method. The modulus of elasticity was the highest at 235 GPa in the milled specimen. In particular, the 3D printing group showed a difference in yield strength and elongation according to the build direction. The introduction of various advanced technologies and digital equipment is expected to bring high prospects for the growth of the dental market.

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.

We identified 1218 Campylobacter coli isolates from fecal and carcass samples of pigs (n = 643) and chickens (n = 575) between 2010 and 2018. About 99% of the isolates were resistant to at least one antimicrobial agent. The isolates exhibited high resistance rates (>75%) to ciprofloxacin, nalidixic acid, and tetracycline. Azithromycin and erythromycin resistance rates were the highest in isolates from pigs (39.7% and 39.2%, respectively) compared to those of chickens (15.8% and 16.3%, respectively). Additionally, a low-to-moderate proportion of the isolates were resistant to florfenicol, gentamicin, clindamycin, and telithromycin. Multidrug resistance (MDR) was found in 83.1% of the isolates, and profiles of MDR usually included ciprofloxacin, nalidixic acid, and tetracycline. We found point mutation (A2075G) in domain V of the 23S rRNA gene in the majority of erythromycin-resistant isolates. Multilocus sequence typing of 137 erythromycin-resistant C. coli isolates revealed 37 previously reported sequence types (STs) and 8 novel STs. M192I, A103VI, and G74A substitutions were frequently noted in the ribosomal proteins L4 or L22. Further, we identified a considerable proportion (>90%) of erythromycin-resistant isolates carrying virulence factor genes: flaA, cadF, ceuE, and VirB. The prudent use of antimicrobials and regular microbiological investigation in food animals will be vital in limiting the public health hazards of C. coli in Korea.

Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ1–42 and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ1–42 leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ1–42 -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ1–42 injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ1–42 injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and “immunohistochemical staining”, mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ1–42-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ1–42 -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ1–42 -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.

Recently, the mTOR signaling has emerged as an important player in the pathogenesis of psoriasis. We previously found that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced psoriatic skin inflammation was related to the inhibition of autophagy in keratinocytes. However, the effects and detailed molecular mechanisms of the mTOR inhibitor rapamycin and TCDD on psoriasis in vivo remain to be elucidated. In this study, we aimed to evaluate the effects of rapamycin and TCDD on skin lesions in imiquimod (IMQ)-induced psoriasis using a mouse model. TCDD aggravated skin inflammation in an IMQ-induced psoriatic mouse model. Furthermore, TCDD increased the expression of aryl hydrocarbon receptor (AHR), CYP1A1, proinflammatory cytokines, oxidative stress markers (NADPH oxidase (Nox) 2, Nox4), and phosphorylated P65NF-ĸB, whereas the expression of autophagy-related factors and the antioxidant marker nuclear factor-erythroid 2-related factor 2 (NRF2) decreased. Rapamycin reduced the aggravated skin inflammation induced by TCDD and restored TCDD-induced autophagy suppression and the increase of AHR expression, oxidative stress, and inflammatory response in the skin lesions of a psoriatic mouse model. In conclusion, we demonstrated that rapamycin alleviates TCDD-induced aggravated dermatitis in mice with imiquimod-induced psoriasis-like dermatitis through AHR and autophagy modulation.

Intestinal commensal bacteria are considered good indicators for monitoring antimicrobial resistance. We investigated the antimicrobial resistance profiles and resistance trends of Enterococcus faecium and Enterococcus faecalis isolated from food animals in Korea between 2010 and 2019. E. faecium and E. faecalis, isolated from chickens and pigs, respectively, presented a relatively high resistance rate to most of the tested antimicrobials. We observed high ciprofloxacin (67.9%), tetracycline (61.7%), erythromycin (59.5%), and tylosin (53.0%) resistance in E. faecium isolated from chickens. Similarly, more than half of the E. faecalis isolates from pigs and chickens were resistant to erythromycin, tetracycline and tylosin. Notably, we observed ampicillin, daptomycin, tigecycline and linezolid resistance in a relatively small proportion of enterococcal isolates. Additionally, the enterococcal strains exhibited an increasing but fluctuating resistance trend (p < 0.05) to some of the tested antimicrobials including daptomycin and/or linezolid. E. faecalis showed higher Multidrug resistance (MDR) rates than E. faecium in cattle (19.7% vs. 8.6%, respectively) and pigs (63.6% vs. 15.6%, respectively), whereas a comparable MDR rate (≈60.0%) was noted in E. faecium and E. faecalis isolated from chickens. Collectively, the presence of antimicrobial-resistant Enterococcus in food animals poses a potential risk to public health.

Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells.

In this study, the anomaly analysis of Alzheimer’s disease using positron emission tomography (PET) images using an unsupervised proposed adversarial model is investigated. The model consists of three parts: a parallel-network encoder, which is comprised of a convolutional pipeline and a dilated convolutional pipeline that extracts global and local features and concatenates them, a decoder that reconstructs the input image from the obtained feature vector, and a discriminator that distinguishes if the input image image is real or fake. The hypothesis is that if the proposed model is trained with only normal brain images, the corresponding construction loss for normal images should be minimal. However, if the input image belongs to a class that is designated as an anomaly that which the model is not trained with, then the construction loss will be high. This will reflect during the anomaly score comparison between the normal and the anomalous image. A multi-case analysis is performed for three major classes using the Alzheimer’s Disease Neuroimaging Initiative dataset, Alzheimer’s disease, mild cognitive impairment, and normal control. The base parallel-encoder network shows better classification accuracy than the benchmark models, and the proposed model that is built on the parallel model outperforms the benchmark anomaly detection models. The proposed model gave out 96.03% and 75.21% in classification and area under the curve score, respectively. Additionally, a qualitative evaluation done by using Fréchet inception distance gave a better score than the state-of-the-art by three points.

When analyzing ship accidents, there may be doubts whether appropriate countermeasures had been taken to prevent known types of accidents. This study aimed to suggest possible solutions by investigating the status and issues associated with the implementation of countermeasures using importance–performance analysis (IPA), Borich’s needs assessment, and locus for focus models based on previously identified causes of the ship accidents. As a result, firstly, we confirmed that there is a need to enhance education and training on specific knowledge, understanding, and proficiency (KUP) regarding ship stability, emergency response, and type specific training. Secondly, we confirmed that there is a need for a system of monitoring a seafarer’s KUP even while onboard a vessel—that is, after completion of identified training. Additionally, it is necessary to improve the seafarers’ working environment, which is subject to regulations. Thirdly, difficulties in solving wrong practice parts of safety and efficiency, such as the costs associated with implementation of safety regulations, were identified as the main reasons for the causes of the “not amended yet” sector after accidents. Lastly, the tools that were employed in this analysis can be used to confirm the implementation status of the actions to be taken after a ship accident.

Targeted therapy based on natural compounds is one of the best approaches against non-small cell lung cancer. Ursolic acid (UA), a pentacyclic triterpenoid derived from medicinal herbs, has anticancer activity. Studies on the molecular mechanism underlying UA’s anticancer activity are ongoing. Here, we demonstrated UA’s anticancer activity and the underlying signaling mechanisms. We used Western blotting and real-time quantitative polymerase chain reaction for molecular signaling analysis. We also used in vitro angiogenesis, wound healing, and invasion assays to study UA’s anticancer activity. In addition, we used tumorsphere formation and chromatin immunoprecipitation assays for binding studies. The results showed that UA inhibited the proliferation of A549 and H460 cells in a concentration-dependent manner. UA exerted anticancer effects by inducing G0/G1 cell cycle arrest and apoptosis. It also inhibited tumor angiogenesis, migration, invasion, and tumorsphere formation. The molecular mechanism underlying UA activity involves UA’s binding to epidermal growth factor receptor (EGFR), reducing the level of phospho-EGFR, and thus inhibiting the downstream JAK2/STAT3 pathway. Furthermore, UA reduced the expressions of vascular endothelial growth factor (VEGF), metalloproteinases (MMPs) and programmed death ligand-1 (PD-L1), as well as the formation of STAT3/MMP2 and STAT3/PD-L1 complexes. Altogether, UA exhibits anticancer activities by inhibiting MMP2 and PD-L1 expression through EGFR/JAK2/STAT3 signaling.

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.