Search

Abstract Background Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. Results CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. Conclusion The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.

Abstract Fatigue is one of the common symptoms in individuals with diseases or disorders, significantly affecting quality of life (QoL) and the prognosis of diseases. This study aimed to comprehensively compare the features of fatigue across a wide range of diseases. We systematically searched the PubMed and Cochrane Library databases from inception to March 31st, 2021, and conducted a meta-analysis to generate precise estimates. The analyses were stratified by classification of diseases, gender, and severity of fatigue (moderate and severe), and study quality was assessed using the Newcastle–Ottawa Scale (NOS). In total, 214 articles (233 prevalence data) met our eligibility criteria, covering 102,024 participants (mean 438 ± 1,421) across 88 diseases. Among these, seventy-eight data sets (52,082 participants) and thirty-nine data sets (10,389 participants) reported gender- and severity-related fatigue prevalence. The overall prevalence among subjects with 88 diseases was 49.4% [95% CI 46.9–52.1]. According to the International Classification of Diseases-10 (ICD-10) classification, the highest prevalence of fatigue (65.9% [95% CI 54.9–79.6]) was observed in patients with mental/behavioral diseases, whereas the lowest prevalence (34.7% [95% CI 24.5–49.2]) was found among those with circulatory system diseases. A slight female dominance (43.5% vs. 49.8%) was observed in the total data, with the most notable female predominance (1.8-fold) seen in patients with low back pain. The top disease groups with a moderate to severe level of fatigue included gastroparesis (92.3%), pulmonary hypertension (90.0%), chronic obstructive pulmonary disease (COPD, 83.2%), and multiple sclerosis (80.0%). These results are the first to comprehensively show the comparative features of fatigue prevalence among subjects across 88 diseases. Our findings provide valuable reference data for future research on fatigue and for the management of patients with fatigue. Prospero registration number: CRD42021270494

Background General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. Methods A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Results In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. Conclusions In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Abstract Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Abstract While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreER T2 ; Hif1a fl/fl ) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER T2 ; Hif1a fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

Background Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes. Methods We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin. Results Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. Conclusion We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Summary: Background: Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model. Methods: We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction. Findings: Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression. Interpretation: Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection. Funding: This research was funded by the National Research Foundation of Korea, the Korea Research Institute of Bioscience and Biotechnology, and the Korea National Institute of Health.

Background Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. Methods and Results Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all‐cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6–35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78–0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71–0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end‐systolic volume index, and lower biventricular global function index as independent predictors of death. A risk‐scoring algorithm dividing patients into low‐risk (score ≤4) versus high‐risk (score >4) groups was validated to effectively discriminate risk of death (15‐year survival of 95% versus 74%, respectively; P

Abstract Background Krüppel-like factor 10 (KLF10) is involved in a positive feedback loop that regulates transforming growth factor β (TGFβ) signaling, and TGFβ plays an important role in the pathogenesis of liver disease. Here, we investigated whether KLF10 deletion affects the development of liver fibrosis and hepatocellular carcinoma (HCC). Methods We induced KLF10 deletion in C57BL/6 mice. Liver fibrosis was induced by feeding a diet high in fat and sucrose (high-fat diet [HFD]), whereas HCC was produced by intraperitoneal administration of N-diethylnitrosamine (DEN). An in vitro experiment was performed to evaluate the role of KLF10 in the cancer microenvironment using Hep3B and LX2 cells. An immunohistochemical study of KLF10 expression was performed using human HCC samples from 60 patients who had undergone liver resection. Results KLF10 deletion resulted in an increased DEN-induced HCC burden with significant upregulation of SMAD2, although loss of KLF10 did not alter HFD-induced liver fibrosis. DEN-treated mice with KLF10 deletion exhibited increased levels of mesenchymal markers (N-cadherin and SNAI2) and tumor metastasis markers (matrix metalloproteinases 2 and 9). KLF10 depletion in Hep3B and LX2 cells using siRNA was associated with increased invasiveness. Compared with co-culture of KLF10-preserved Hep3B cells and KLF10-intact LX2 cells, co-culture of KLF10-preserved Hep3B cells and KLF10-depleted LX2 cells resulted in significantly enhanced invasion. Low KLF10 expression in resected human HCC specimens was associated with poor survival. Conclusion The results of this study suggest that loss of KLF10 facilitates liver cancer development with alteration in TGFβ signaling.

Abstract Complement-dependent cytotoxicity (CDC), which eliminates aberrant target cells through the assembly and complex formation of serum complement molecules, is one of the major effector functions of anticancer therapeutic antibodies. In this study, we discovered that breaking the symmetry of natural immunoglobulin G (IgG) antibodies significantly increased the CDC activity of anti-CD20 antibodies. In addition, the expression of CD55 (a checkpoint inhibitor in the CDC cascade) was significantly increased in a rituximab-resistant cell line generated in-house, suggesting that CD55 overexpression might be a mechanism by which cancer cells acquire rituximab resistance. Based on these findings, we developed an asymmetric bispecific antibody (SBU-CD55 × CD20) that simultaneously targets both CD55 and CD20 to effectively eliminate rituximab-resistant cancer cells. In various cancer cell lines, including rituximab-resistant lymphoma cells, the SBU-CD55 × CD20 antibody showed significantly higher CDC activity than either anti-CD20 IgG antibody alone or a combination of anti-CD20 IgG antibody and anti-CD55 IgG antibody. Furthermore, the asymmetric bispecific antibody (SBU-CD55 × CD20) exhibited significantly higher CDC activity against rituximab-resistant cancer cells compared to other bispecific antibodies with symmetric features. These results demonstrate that enhancing CDC with an asymmetric CD55-binding bispecific antibody could be a new strategy for developing therapeutics to treat patients with relapsed or refractory cancers.

Newborn incompetence of the sphincter of Oddi is rare. While there are many causes of reflux of air or ingested contrast material into the biliary tree in adults, in the newborn, it is usually due to incompetence of the sphincter of Oddi associated with partial or complete duodenal obstruction. This paper presents upper gastrointestinal series findings of incompetence of the sphincter of Oddi associated with duodenal stenosis in a 3-day-old newborn. If pneumobilia is identified in the newborn, although the possibility is low, clinicians should consider incompetence of the sphincter of Oddi with duodenal obstruction as well as portal vein gas.

PURPOSE This study aims to provide empirical foundational data for the development of a new profit model in Korean professional baseball. It does so by examining the influence of professional baseball NFT product attributes on customer perceptions of value, satisfaction, and purchase intention. METHODS Data were collected from consumers who have experience purchasing KBOLLECT. A total of 363 samples were collected for analysis. Surveys were utilized for data collection, encompassing 39 items that measured product characteristics, perceived value, satisfaction, purchase intention, and demographic information. Using the collected data, various statistical analyses were conducted including descriptive statistics, exploratory factor analysis, reliability analysis, correlation analysis and multiple regression using SPSS version 21. The ensuing results from the correlation analysis and multiple regression analysis are as follows. RESULTS Product features, including aesthetics, symbolism, and scarcity, had a positive impact on consumer’s perceived emotional value. Moreover, product features, encompassing aesthetics, symbolism, scarcity, and creativity played a significant role in enhancing consumer’s perceived economic value. Furthermore, product attributes such as aesthetics, symbolism, and creativity positively contributed to consumer’s perceived social value. Similarly, product features comprising aesthetics, scarcity, creativity, and symbolism positively affected consumer’s perceived intellectual value. Additionally, the research revealed that product features related to aesthetics, symbolism, creativity, and scarcity were instrumental in bolstering consumer. Importantly, these very attributes, including aesthetics, symbolism, scarcity, and creativity, exhibited a positive influence on consumers’ purchase intentions. CONCLUSIONS In conclusion, this study underscores the substantial impact of professional baseball NFT product characteristics on consumers’ perceptions, satisfaction, and purchase intentions. To maintain enduring relationships with consumers who engage with professional baseball NFT products, it is essential to fortify these product attributes and offer diverse services utilizing them.

The development of new functional foods that can potentially reduce the risk of diseases, such as osteoporosis, has received increasing attention in recent years. Here we demonstrated that silk sericin-based functional food (SSBF) exerted preventive and therapeutic effects against bone loss. Sericin isolated at 70 °C for 60 min from the cocoon of Bombyx mori stimulated osteoblast differentiation by increasing osteoblastic gene expression while inhibiting receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in vitro. Micro-computed tomography analysis revealed that pre- and post-oral administration of SSBF increased bone mass in ovariectomized mouse model in vivo. Furthermore, dynamic bone histomorphometry analysis revealed that SSBF enhanced osteoblast activity and suppressed bone resorption by reducing the number of osteoclasts. These findings indicated the potential role of SSBF in preventing and being a therapeutic candidate for osteoporosis.

Abstract The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1β and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1β, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1β signaling-induced inflammation and enhancing NK cell activity.

Abstract Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2–47.2) of fatigue prevalence. The total CRF prevalence including ‘mild’ level of fatigue was 70.7% (95% CI 60.6–83.3 from 37 data). The prevalence of ‘severe’ fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1–31.3) before treatment, 33.8% (95% CI 27.7–41.2) ongoing treatment, and 24.1% (95% CI 18.6–31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for ‘severe’ CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for ‘severe’ CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of ‘severe’ fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.

Objectives The Korea Disease Control and Prevention Agency promotes vaccination by regularly providing information on its benefits for reducing the severity of coronavirus disease 2019 (COVID-19). This study aimed to analyze the number of averted severe COVID-19 cases and COVID-19-related deaths by age group and quantify the impact of Republic of Korea’s nationwide vaccination campaign. Methods We analyzed an integrated database from the beginning of the vaccination campaign on February 26, 2021 to October 15, 2022. We estimated the cumulative number of severe cases and COVID-19-related deaths over time by comparing observed and estimated cases among unvaccinated and vaccinated groups using statistical modeling. We compared daily age-adjusted rates of severe cases and deaths in the unvaccinated group to those in the vaccinated group and calculated the susceptible population and proportion of vaccinated people by age. Results There were 23,793 severe cases and 25,441 deaths related to COVID-19. We estimated that 119,579 (95% confidence interval [CI], 118,901–120,257) severe COVID-19 cases and 137,636 (95% CI, 136,909–138,363) COVID-19-related deaths would have occurred if vaccination had not been performed. Therefore, 95,786 (95% CI, 94,659–96,913) severe cases and 112,195 (95% CI, 110,870–113,520) deaths were prevented as a result of the vaccination campaign. Conclusion We found that, if the nationwide COVID-19 vaccination campaign had not been implemented, the number of severe cases and deaths would have been at least 4 times higher. These findings suggest that Republic of Korea’s nationwide vaccination campaign reduced the number of severe cases and COVID-19 deaths.

The accessory tendon of the extensor hallucis longus is a common type of extensor hallucis longus variation. This is a case of a 38-year-old female patient who initially considered conservative treatment for a suspected partial rupture, but finally underwent surgery after being diagnosed with a complete rupture of the main tendon and accessory tendon medial to the main tendon on MRI scan.

Rice bodies are commonly detected in adults with rheumatoid arthritis and rarely occur in children. An 11-year-old female adolescent who visited our hospital for evaluation of knee pain underwent a MRI scan, which revealed an intra-articular mass. Arthroscopic examination of the mass confirmed conglomerated rice bodies. We report a case of rice bodies that clinically presented as intra-articular masses.

Abstract Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.

In general, neuroendocrine cancer develops in the digestive or respiratory tract, and when it is found in other organs, it is often due to metastasis. Primary neuroendocrine carcinoma of the breast occurs very rarely, and the exact clinical picture, radiological findings, treatment and prognosis are not well known. Furthermore, only a small number of literature reports have been published. Here, we report the imaging findings of primary neuroendocrine carcinoma in the breast of a 51-year-old female, along with a literature review.

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

PURPOSE The purpose of this study was to understand the current market trend for golf apparel rental services and to present basic data to revitalize the golf apparel rental service market and prepare continuous growth plans. METHODS The following keywords were selected for data collection: "golf wear + rental (렌탈)," "golf wear + rental (대여)," "golf apparel + rental (렌탈)," and "golf apparel + rental (대여).“ The analysis period was limited to two years and seven months from January 1, 2020 to July 31, 2022, when COVID-19 began. The analysis was focused on the top 60 keywords to simplify the network. RESULTS Various keywords were extracted through text mining, TF-IDF, connection centrality, emotional analysis, and semantic network analysis of big data analysis. These were then categorized into four factors: “golf apparel rental service,” “self-expression and authentication,” “sharing economy,” and “emotion.” CONCLUSIONS The results of this study show that young golfers are unreluctant and are generally positive in renting golf apparel. Therefore, if the growing paradigm of the consumption behavior of MZ-generation golfers is recognized and analyzed and the requirements are continuously satisfied through various strategies, there will be a higher possibility to help expand the golf apparel rental market.

Abstract Background Silk sericin is an active ingredient in bone grafts. However, the optimal scaffold for silk sericin has yet to be identified. Method A critical-sized bone defect model in rat calvaria was used to evaluate bone regeneration. Silk sericin from Yeonnokjam, Bombyx mori, was incorporated into gelatin (group G, n = 6) and collagen (group C, n = 6). Bone regeneration was evaluated using micro-computed tomography (mCT) and histology. Results Group C showed a larger bone volume than group G in the mCT analysis (P = 0.001). Histological analysis showed a larger area of bony defects in group G than in group C. The bone regeneration area in group C was significantly larger than that in group G (P = 0.003). Conclusion Compared with gelatin, collagen shows better bone regeneration in silk sericin-based bone grafts.

In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin–angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Metaplastic carcinoma of the breast is a heterogeneous group of neoplasms with mixed epithelial and mesenchymal differentiation. Metaplastic carcinoma of the breast is a rare and aggressive malignancy, with high recurrence and metastasis. Metaplastic carcinoma with chondroid differentiation is an uncommon subtype that tends to have a relatively good prognosis than that of other subtypes. We report the imaging features of three cases of pathologically proven metaplastic carcinoma with chondroid differentiation as follows: a high-density mass with amorphous or coarse heterogeneous calcifications on mammography; a microlobulated or partially indistinct, complex cystic, and solid mass on sonography; and a relatively circumscribed or partially indistinct, irregular mass with heterogeneous T2 high-signal intensity and heterogeneous or rim enhancement with initial fast enhancement and delayed washout on MRI.

Background/Aim Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis. Methods The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry. Results The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers. Conclusions The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis.

BackgroundFatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population.MethodsPubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (

Abstract The use of endobiliary radiofrequency ablation (RFA) to generate a benign biliary stricture (BBS) model has a significant reproducibility problem. The aims of this animal study were to create an optimal BBS model using endobiliary RFA and determine the best way to develop it. The first step was performed on the common bile duct (CBD) of 10 miniature pigs using endoscopic RFA with a target temperature-controlled mode (80 ℃, 7 W for 90 s). The second step was performed on the CBD of five miniature pigs to understand more about the time-dependent changes in BBS development and the causes of adverse events. Using the conditions and techniques identified in the previous steps, the third step was conducted to create an optimal BBS model in 12 miniature pigs. In the first trial, four out of 10 animals died (40%) after the procedure due to cholangitis-induced sepsis. Based on this, biliary obstruction was prevented in further steps by placing a biliary plastic stent after RFA application. Histologic examinations over time showed that a severe abscess developed at the RFA application site on the fifth day, followed by fibrosis on the tenth day, and completion on the twentieth day. In the third trial, 11 animals survived (91.7%), the average BBS fibrotic wall thickness was 1107.9 µm (763.1–1864.6 µm), and the degree of upstream biliary dilation was 14.4 mm (11.05–20.7 mm). In conclusion, endobiliary RFA combined with a biliary plastic stent resulted in a safe and reproducible BBS animal model.

Spinal epidermoid cysts are extremely rare benign tumors and can be congenital or acquired. Acquired spinal epidermoid cysts are found in the lumbosacral region. To our knowledge, no case of epidermoid cyst related to spinal cord stimulator insertion has yet been reported. We report the MRI findings of a rare case of thoracic intradural epidermoid cyst acquired after spinal cord stimulator insertion in a 50-year-old female.

We report a case of intra-abdominal seminoma in an undescended testis, focusing on the radiological clues for diagnosis on computed tomography. A 49-year-old man visited our hospital with a palpable abdominal mass and underwent abdominopelvic computed tomography. Computed tomography demonstrated an ovoid, mildly enhanced, well-defined mass measuring 21 × 16 × 9 cm in the small bowel mesentery mimicking a mass of mesenteric origin. However, a vascular structure was observed in the left posterior aspect of the mass. The vascular structure originated from the inferior posterior part of the mass and ran cranially. The artery subsequently united to the aorta, and the vein united to the left renal vein. We identified the artery and vein as the testicular artery and vein, respectively. We also noted the absence of a left spermatic cord in the left inguinal canal. Therefore, we concluded that the mass originated from the left undescended testis. The patient underwent surgery, and the mass was removed with the testicular vessels; the resected testicular vein was mostly filled with thrombus. On pathological examination, the mass was confirmed to be a seminoma in the undescended testis.

Abstract Treatment of benign biliary strictures (BBS) using fully covered self-expandable metal stents (FCSEMS) has a high success rate, but recurrence can occur. Corticosteroids may be useful based on their anti-fibrotic and anti-inflammatory effects. We investigated the safety and efficacy of corticosteroid-eluting FCSEMS in an animal model. BBSs were created by radiofrequency ablation in 12 mini-pigs. Four weeks later, FCSEMS coated with 0 mg (control), 15 mg (steroid 1 × group), or 30 mg (steroid 2 × group) triamcinolone were inserted endoscopically. The in vitro drug release assay revealed that the optimal stent had 15 mg of triamcinolone and a hydrophilic membrane. No transmural necrosis or perforation occurred in any animal. Fibrous wall thickness tended to decrease macroscopically and microscopically in a triamcinolone dose-dependent manner (control vs. steroid 2 × group: 773.1 vs. 468.5 µm, P = 0.037). Thickness also decreased over time in the steroid 2 × group (3 days vs. 4 weeks: 907.9 vs. 468.5 µm, P = 0.025). Blood parameters tended to improve after stent insertion. In a porcine BBS model, steroid-eluting FCSEMS showed potential as a safe and effective treatment modality to reduce fibrotic tissue. Studies are required to confirm their safety and efficacy in humans with refractory BBS.

PURPOSE This study aimed to identify the decision-making process for consumers participating in sports centers based on an extended goal-directed behavior model (EMGB), and to provide empirical data for establishing effective operation strategies for sports centers, including additional risk perception of consumers during pandemic. METHODS A total of 446 surveys were used as the final sample. For data analysis, SPSS 21.0 and AMOS 21.0 were used for frequency analysis, correlation analysis, confirmatory factor analysis, and structural equation model analysis. RESULTS Except for hypothesis 2 and 9, all of the hypothesis were chosen. CONCLUSIONS The findings suggested that extended goal-oriented behavior models can increase consumers' cognitive and emotional factors through emotional aspirations, suggesting that a lower risk perception of COVID19 increases their desire to participate in sports centers, and provides academic fundamental data on how to increase and activate sports centers.

Objectives Analysis of overseas cases, and evaluated feasibility of setting permissible discharge standards method in domestic integrated environmental permission system. Through the evaluation results, it is intended to improvement the method of setting permissible discharge standards. Methods The method of setting permissible discharge standards in the United states, Germany and United kingdom were compared, and evaluated feasibility of the method was conducted by applying nitrogen oxide actual emission data. In addition, analyzed problems derived from the case of integrated permits and suggested solutions. Results and Discussion It was confirmed that permissible discharge standards for pollutants were established by reflecting characteristics of country. As a result of evaluated feasibility of the permissible discharge standards setting method, when the criteria set by referring to overseas evaluation standards were applied rather than domestic evalution criteria, the number of stacks that required setting permissible discharge standard through discharge impact analysis tended to increase. Through this, it was confirmed that the method of setting permissible discharge standards in domestic system was not excessively strengthened. In standard modeling(AERMOD) of discharge impact anaysis, it was confirmed that topographical data and stack information had a great influence on calculation of process contribution. Conclusion In order to improve domestic integrated environmental permission system, it is necessary to consider reflecting effective stack height in AERMOD, setting the evaluation of ultrafine dust(PM-2.5) or Ozone(O3) with reference to the United States evaluation method or domestric environmental impact assessment evaluation method, applying a simplified analysis to company where the pollutants emitted have little effect on the air, applying ADJ_U * in order to prevent AERMOD pollutants from being overestimated at high concentrations when the atmosphere is stable and the wind speed is low.

Prunus Linnaeus 1753 species include many economically important fruit crops, of which plumcot is generated by inter-species crossing between Prunus salicina Lindley 1830 × Prunus armeniaca Linnaeus 1753. In this study, the complete chloroplast genome of Korean plumcot cultivar ‘Harmony’ was characterized through the de novo assembly of Nanopore and Illumina sequencing data. The chloroplast genome is a circular molecule of 157,916 bp length with 36.75% GC content and has a total of 113 genes including 79 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. Phylogenetic analysis with protein-coding sequences of chloroplast genome revealed that ‘Harmony’ showed closer to P. salicina than P. armeniaca.

Objectives The Environmental Pollution Facility Act was implemented to effectively reduce pollutants that could be generated in the business establishment, centering on emission facilities, from the Media Act, which had been managed in the aspect of follow-up management. Accordingly, the change in the generation of air pollutants after the integrated permit in coal-fired power plants was examined. Methods Air pollutant emission standards were analyzed for business establishment that use coal, a solid fuel, as fuel among power plants that have completed integrated permits. Results and Discussion The standards suggested by the Act on the Integrated Control of Pollutant-Discharging Facilities have numerically higher values than the existing Clean Air Conservation Act Standards, but there is a limit to evaluating only with simple standards because permit standards are given through emission impact analysis. As a result of a comparison through the emission impact analysis, it was found that 10 plants were given stricter permit standards for sulfur oxides and nitrogen oxides by 22% and for dust by 10% at 8 business establishment. Conclusion The level of pollution on the surrounding location status is evaluated, and permission standards are granted. It was confirmed that the emission impact analysis method under the Act On The Integrated Control of Pollutant-Discharging Facilities can be applied as a more strictly manageable means than the existing standards under the Clean Air Conservation Act.

Abstract Background Skeletal muscle atrophy is a severe condition that involves loss of muscle mass and quality. Drug intake can also cause muscle atrophy. Biguanide metformin is the first‐line and most widely prescribed anti‐diabetic drug for patients with type 2 diabetes. The molecular mechanism of metformin in muscle is unclear. Methods Myostatin expression was investigated at the protein and transcript levels after metformin administration. To investigate the pathways associated with myostatin signalling, we used real‐time polymerase chain reaction, immunoblotting, luciferase assay, chromatin immunoprecipitation assay, co‐immunoprecipitation, immunofluorescence, primary culture, and confocal microscopy. Serum analysis, physical performance, and immunohistochemistry were performed using our in vivo model. Results Metformin induced the expression of myostatin, a key molecule that regulates muscle volume and triggers the phosphorylation of AMPK. AMPK alpha2 knockdown in the background of metformin treatment reduced the myostatin expression of C2C12 myotubes (−49.86 ± 12.03%, P 3.12‐fold ± 0.13, P 3.3‐fold, P

Abstract This study investigated the correlation between pancreatic fibrosis (PF) and development of pancreoprivic diabetes after pancreaticoduodenectomy (PD). Ninety-five patients who underwent PD at Gangnam Severance Hospital between 2014 and 2017 were enrolled. PF grade was evaluated with alpha-smooth muscle actin (SMA) and Masson’s trichrome (TRC) staining. New-onset pancreoprivic diabetes and recurrence of disease were evaluated using fasting blood glucose measurement and radiography taken at 3-month intervals. Sixty-one patients did not have preoperative diabetes, however, 40 (65.6%) patients developed pancreoprivic diabetes after PD. High-grade PF was more common in the diabetes group than in the normal group (SMA, 42.5% vs. 28.6%, P = 0.747; TRC, 47.5% vs. 28.6%, P = 0.361). The 1-year cumulative incidence of hyperglycemia/pancreoprivic diabetes was higher with high-grade PF than low-grade PF (SMA, 94.4% vs. 73.0%, P = 0.027; TRC, 89.3% vs. 75.0%, P = 0.074). The SMA-TRC combined high-grade group had a higher proportion of primary pancreatic disease than the combined low-grade group (90.0% vs. 37.5%, P = 0.001). The 5-year disease-free survival of patients with pancreatic cancer was worse with high-grade PF than low-grade PF (SMA, 24.5% vs. 66.3%, P = 0.026; TRC, 23.6% vs. 58.4%, P = 0.047). In conclusion, patients with severe PF are more likely to develop pancreoprivic diabetes after PD and have worse disease-free survival.

Background. Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is aimed at updating the safety data of PCSK9 inhibitors. Methods. We assessed the relative risk for all treatment-related adverse events, serious adverse events, diabetes-related adverse events, and neurocognitive and neurologic adverse events with PCSK9 inhibitors compared to controls (placebo or ezetimibe). In addition, we conducted a meta-analysis to quantitatively integrate and estimate the adverse event rates in long-term studies. Results. There were no significant differences between PCSK9 inhibitors and controls in the relative risk analysis. In a subgroup analysis of each PCSK9 inhibitor, alirocumab treatment significantly reduced the risk of serious adverse events compared to control treatment (risk ratio RR=0.937; 95% confidence interval (CI), 0.896–0.980), but no significant difference was observed with evolocumab treatment (RR=1.003; 95% CI, 0.963–1.054). Moreover, alirocumab treatment afforded a significant reduction in the risk of diabetes-related adverse events compared to control treatment (RR=0.9137; 95% CI, 0.845–0.987). The overall incidence (event rate) of long-term adverse events was 75.1% (95% CI, 71.2%–78.7%), and the incidence of serious long-term event rate was 16.2% (95% CI, 11.6%–22.3%). Conclusions. We suggest that alirocumab and evolocumab are generally safe and well tolerated and that their addition to background lipid-lowering therapy is not associated with an increased risk of adverse events or toxicity.

Hepatocellular carcinoma (HCC) has heterogeneous molecular and pathological features and biological behavior. Large-scale genetic studies of HCC were accumulated, and a pathological-molecular classification of HCC was proposed. Approximately 35% of HCCs can be classified into distinct histopathological subtypes according to their molecular characteristics. Among recently identified subtypes, macrotrabecular massive HCC, neutrophil-rich HCC, vessels encapsulating tumor clusters HCC, and progenitor phenotype HCC (HCC with CK19 expression) are associated with a poor prognosis, whereas the lymphocyte-rich HCC subtype is related to a better prognosis. This review provides up-to-date knowledge on the pathological diagnosis of HCC according to the updated World Health Organization Classification of Digestive System Tumors 5th ed.

Purpose The purpose of this study was to find out what young amateur golfers consider the most when purchasing golf apparel and to find out the Importance-Performance attributes when choosing golf apparel. Methods Amateur golfers in their 20s through 40s who have purchased golf clothing directly were selected as the subject. A total of 350 questionnaires were distributed using the purposive sampling method, and 331 copies as a final validity sample. For data analysis exploratory factor analysis Cronbach’α, frequency analysis, and Importance-Performance analysis by using SPSS 21.0. Results First, except for ‘fancy design’, ‘water-proof function’, ‘elasticity comfort’, ‘brand name’ there were significant differences between importance and satisfaction of selection attribute. Second, ‘harmonic colors’, ‘has its own characteristics’, ‘expressing beauty’, ‘elasticity comfort’ were analyzed to be situated in quadrant Ⅰ. Third, ‘fancy design’, ‘water-proof function’, ‘temperature maintenance function’, ‘elasticity and durability’, ‘brand name’, ‘high-priced yet popular brand’, ‘popular brand’ were analyzed to be situated in quadrant Ⅱ. Fourth, ‘comfortable to wear’, ‘convenient for physical activity’ were analyzed to be situated in quadrant Ⅲ. Fifth, ‘can be also worn for outdoor wear’, ‘wear for gathering’, ‘wear as daily attire’ were analyzed to be situated in quadrant Ⅳ. Conclusions The results will be the basis for effective target marketing on young amateur golfers who are rapidly emerging and will be able to grasp the characteristics of golf apparel that they really want.

Ascariasis is an intestinal disease caused by Ascaris lumbricoides. Most patients with ascariasis are asymptomatic; however, the presence of many larvae in the bowel can cause gastrointestinal complications, such as intestinal obstruction, obstructive jaundice, cholangitis, cholecystitis, and pancreatitis. Herein, we report a case of ascariasis presenting as hematoma and active bleeding in the sigmoid mesocolon of a 74-year-old man on computed tomography (CT). Sigmoid colon perforation was also detected on follow-up CT. Laparoscopic low anterior resection was performed; there was a large hematoma in the sigmoid mesocolon. Roundworms were microscopically identified in the mesenteric adipose tissue. The clinical and CT findings of this unusual presentation of ascariasis revealed serial complications during parasite migration from the intestinal lumen to the peritoneal cavity.

Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis. We demonstrated that vimentin null (Vim–/–) mouse peritoneal macrophages take up less oxidized LDL (oxLDL) than vimentin wild type (Vim+/+) macrophages. Despite less uptake of oxLDL in Vim–/– macrophages, Vim+/+ and Vim–/– macrophages did not show difference in expression of CD36 known to mediate oxLDL uptake. However, CD36 localized in plasma membrane was 50% less in Vim–/– macrophages than in Vim+/+ macrophages. OxLDL/CD36 interaction induced protein kinase A (PKA)-mediated vimentin (Ser72) phosphorylation. Cd36–/– macrophages did not exhibit vimentin phosphorylation (Ser72) in response to oxLDL. Experiments using phospho-mimetic mutation of vimentin revealed that macrophages with aspartate-substituted vimentin (V72D) showed more oxLDL uptake and membrane CD36. LDL receptor null (Ldlr–/–) mice reconstituted with Vim–/– bone marrow fed a western diet for 15 weeks showed 43% less atherosclerotic lesion formation than Ldlr–/– mice with Vim+/+ bone marrow. In addition, Apoe–/–Vim–/– (double null) mice fed a western diet for 15 weeks also showed 57% less atherosclerotic lesion formation than Apoe–/– and Vim+/+mice. We concluded that oxLDL via CD36 induces PKA-mediated phosphorylation of vimentin (Ser72) and phosphorylated vimentin (Ser72) directs CD36 trafficking to plasma membrane in macrophages. This study reveals a function of vimentin in CD36 trafficking and macrophage foam cell formation and may guide to establish a new strategy for the treatment of atherosclerosis.

The potential use of wastewater sludge as a biosorbent for the removal of various metals and metalloids from aqueous solutions was investigated. The sludge was immobilized in a rod shape with chitosan to improve sorption capacity and solid–liquid separation ability. An optimal condition for the production of rod-shaped chitosan-immobilized sludge (RCS) was determined by considering the biosorbent production potential and As(V) removal efficiency. The optimal sludge and chitosan contents and RCS thickness were 6.0%, 4.0%, and 0.2–0.3 mm, respectively. The anion removal performance of RCS was investigated for As(V), Cr(VI), and Mn(VII), and the cation removal performance was investigated for Cd(II). Pseudo-first-order and pseudo-second-order models adequately explained the kinetic data for the RCS, while the Langmuir and Freundlich models explained the equilibrium data for the RCS. These results showed that RCS has a higher adsorption capacity for anions than for cations. The results also indicated that electrostatic attraction or ion exchange is the main mechanism for metal/metalloid removal by RCS, except for the case of Mn(VII) where an adsorption-coupled reduction mechanism may be suggested.

Hypothalamic Kiss1 neurons control gonadotropin-releasing hormone release through the secretion of kisspeptin. Kiss1 neurons serve as a nodal center that conveys essential regulatory cues for the attainment and maintenance of reproductive function. Despite this critical role, the mechanisms that control kisspeptin synthesis and release remain largely unknown. Using Drop-Seq data from the arcuate nucleus of adult mice and in situ hybridization, we identified Nescient Helix-Loop-Helix 2 (Nhlh2), a transcription factor of the basic helix-loop-helix family, to be enriched in Kiss1 neurons. JASPAR analysis revealed several binding sites for NHLH2 in the Kiss1 and Tac2 (neurokinin B) 5′ regulatory regions. In vitro luciferase assays evidenced a robust stimulatory action of NHLH2 on human KISS1 and TAC3 promoters. The recruitment of NHLH2 to the KISS1 and TAC3 promoters was further confirmed through chromatin immunoprecipitation. In vivo conditional ablation of Nhlh2 from Kiss1 neurons using Kiss1Cre:Nhlh2fl/fl mice induced a male-specific delay in puberty onset, in line with a decrease in arcuate Kiss1 expression. Females retained normal reproductive function albeit with irregular estrous cycles. Further analysis of male Kiss1Cre:Nhlh2fl/fl mice revealed higher susceptibility to metabolic challenges in the release of luteinizing hormone and impaired response to leptin. Overall, in Kiss1 neurons, Nhlh2 contributes to the metabolic regulation of kisspeptin and NKB synthesis and release, with implications for the timing of puberty onset and regulation of fertility in male mice.

The root of Smilax china L. is used in traditional Korean medicine. We found that the Smilax china L. root extract has strong antimicrobial activity against two Cutibacterium acnes strains (KCTC 3314 and KCTC 3320). The aim of this study was to identify the beneficial properties of Smilax china L. extracts for their potential use as active ingredients in cosmetics for the treatment of human skin acne. The high-performance liquid chromatography (HPLC) and liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC/QTOF/MS) methods were used to obtain the profile of secondary metabolites from the ethyl acetate-soluble fraction of the crude extract. Agar diffusion and resazurin-based broth microdilution assays were used to evaluate antimicrobial activity and minimum inhibitory concentrations (MIC), respectively. Among the 24 metabolites, quercetin, resveratrol, and oxyresveratrol were the most potent compounds against Cutibacterium acnes. Minimum inhibitory concentrations of quercetin, resveratrol, and oxyresveratrol were 31.25, 125, and 250 μg/mL, respectively.

Metaplasia is a well documented and deleterious effect of crude oil components on oysters. This reversible transformation of one cell type to another is a common response to petroleum-product exposure in molluscs. It has been shown experimentally in previous work that eastern oysters (Crassostrea virginica) exposed to petroleum products will exhibit metaplasia of digestive tissues. Here we document for the first time that wild adult oysters inhabiting coastal waters in the northern Gulf of Mexico during and in the aftermath of the Deepwater Horizon oil spill (2010) exhibited metaplasia in both ctenidial (respiratory and suspension feeding) and digestive tract tissues at significantly higher frequencies than geographic controls of C. virginica from Chesapeake Bay. Metaplasia included the loss of epithelial cilia, transformations of columnar epithelia, hyperplasia and reduction of ctenidial branches, and vacuolization of digestive tissues. Evidence for a reduction of metaplasia following the oil spill (2010-2013) is suggestive but equivocal.

With the continued development of artificial intelligence (AI) technology, research on interaction technology has become more popular. Facial expression recognition (FER) is an important type of visual information that can be used to understand a human's emotional situation. In particular, the importance of AI systems has recently increased due to advancements in research on AI systems applied to AI robots. In this paper, we propose a new scheme for FER system based on hierarchical deep learning. The feature extracted from the appearance feature-based network is fused with the geometric feature in a hierarchical structure. The appearance feature-based network extracts holistic features of the face using the preprocessed LBP image, whereas the geometric feature-based network learns the coordinate change of action units (AUs) landmark, which is a muscle that moves mainly when making facial expressions. The proposed method combines the result of the softmax function of two features by considering the error associated with the second highest emotion (Top-2) prediction result. In addition, we propose a technique to generate facial images with neutral emotion using the autoencoder technique. By this technique, we can extract the dynamic facial features between the neutral and emotional images without sequence data. We compare the proposed algorithm with the other recent algorithms for CK+ and JAFFE dataset, which are typically considered to be verified datasets in the facial expression recognition. The ten-fold cross validation results show 96.46% of accuracy in the CK+ dataset and 91.27% of accuracy in the JAFFE dataset. When comparing with other methods, the result of the proposed hierarchical deep network structure shows up to about 3% of the accuracy improvement and 1.3% of average improvement in CK+ dataset, respectively. In JAFFE datasets, up to about 7% of the accuracy is enhanced, and the average improvement is verified by about 1.5%.