Publications by authors named "Yujin Lee"

127 Publications

A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.

Nat Commun 2021 Sep 24;12(1):5631. Epub 2021 Sep 24.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.

Insulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans, mutations in the daf-2/insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, and reproduction. Whether these pleiotropic effects can be dissociated at a specific step in insulin/IGF-1 signaling pathway remains unknown. Through performing a mutagenesis screen, we identified a missense mutation daf-18(yh1) that alters a cysteine to tyrosine in DAF-18/PTEN phosphatase, which maintained the long lifespan and enhanced immunity, while improving the reduced motility in adult daf-2 mutants. We showed that the daf-18(yh1) mutation decreased the lipid phosphatase activity of DAF-18/PTEN, while retaining a partial protein tyrosine phosphatase activity. We found that daf-18(yh1) maintained the partial activity of DAF-16/FOXO but restricted the detrimental upregulation of SKN-1/NRF2, contributing to beneficial physiological traits in daf-2 mutants. Our work provides important insights into how one evolutionarily conserved component, PTEN, can coordinate animal health and longevity.
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http://dx.doi.org/10.1038/s41467-021-25920-wDOI Listing
September 2021

A DNA-derived phage nose using machine learning and artificial neural processing for diagnosing lung cancer.

Biosens Bioelectron 2021 Aug 14;194:113567. Epub 2021 Aug 14.

Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 46241, South Korea; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, United States. Electronic address:

There is a growing interest in electronic nose-based diagnostic systems that are fast and portable. However, existing technologies are suitable only for operation in the laboratory, making them difficult to apply in a rapid, non-face-to-face, and field-suitable manner. Here, we demonstrate a DNA-derived phage nose (DpNose) as a portable respiratory disease diagnosis system requiring no pretreatment. DpNose was produced based on phage colour films implanted with DNA sequences from mammalian olfactory receptor cells, and as a result, it possesses the comprehensive reactivity of these cells. The manipulated surface chemistry of the genetically engineered phages was verified through a correlation analysis between the calculated and the experimentally measured reactivity. Breaths from 31 healthy subjects and 31 lung cancer patients were collected and exposed to DpNose without pretreatment. With the help of deep learning and neural pattern separation, DpNose has achieved a diagnostic success rate of over 75% and a classification success rate of over 86% for lung cancer based on raw human breath. Based on these results, DpNose can be expected to be directly applicable to other respiratory diseases.
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http://dx.doi.org/10.1016/j.bios.2021.113567DOI Listing
August 2021

Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Micro-Simulation Study.

Circulation 2021 Aug 27. Epub 2021 Aug 27.

Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; Department of Food Science and Human Nutrition, University of Thessaly, Volos, Thessaly 38221 Greece.

High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative (NSSRI) proposed government supported voluntary national sugar reduction targets. This intervention's potential health and equity impacts, and cost-effectiveness are unclear. A validated microsimulation model, CVD-PREDICT, coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs and cost-effectiveness of the NSSRI policy. The model was run at the individual-level, incorporating the annual probability of each person's transition between health status based on their risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011-2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from healthcare and societal perspectives. Uncertainty was evaluated in a one-way analysis by assuming 50% industry compliance, and probabilistic sensitivity analyses via a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal healthcare cost savings, stratified by age, race, income and education. Achieving the NSSRI sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150K/QALYs) at 6 years, highly cost-effective (< 50K/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a healthcare perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black and Hispanic, lower income, and less educated Americans. Implementing and achieving the NSSRI sugar reformation targets could generate substantial health gains, equity gains and cost-savings.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053678DOI Listing
August 2021

Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Nat Commun 2021 08 24;12(1):5008. Epub 2021 Aug 24.

Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Republic of Korea.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.
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http://dx.doi.org/10.1038/s41467-021-25324-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385057PMC
August 2021

Longitudinal Plasma Measures of Trimethylamine N-Oxide and Risk of Atherosclerotic Cardiovascular Disease Events in Community-Based Older Adults.

J Am Heart Assoc 2021 Sep 16;10(17):e020646. Epub 2021 Aug 16.

Friedman School of Nutrition Science and Policy Tufts University Boston MA.

Background Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine, and phosphatidylcholine-rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community-based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community-based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography-tandem mass spectrometry (laboratory coefficient of variation, <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression, including time-varying demographics, lifestyle factors, medical history, laboratory measures, and dietary habits. Potential mediating effects and interaction by estimated glomerular filtration rate (eGFR) were assessed. During prospective follow-up, 1766 incident and 897 recurrent ASCVD events occurred. After multivariable adjustment, higher levels of TMAO were associated with a higher risk of incident ASCVD, with extreme quintile hazard ratio (HR) compared with the lowest quintile=1.21 (95% CI, 1.02-1.42; -trend=0.029). This relationship appeared mediated or confounded by eGFR (eGFR-adjusted HR, 1.07; 95% CI, 0.90-1.27), as well as modified by eGFR (-interaction <0.001). High levels of TMAO were associated with higher incidence of ASCVD in the presence of impaired renal function (eGFR <60 mL/min per 1.73 m: HR, 1.56 [95% CI, 1.13-2.14]; -trend=0.007), but not normal or mildly reduced renal function (eGFR ≥60 mL/min per 1.73 m: HR, 1.03 [95% CI, 0.85-1.25]; -trend=0.668). Among individuals with prior ASCVD, TMAO associated with higher risk of recurrent ASCVD (HR, 1.25 [95% CI, 1.01-1.56]; -trend=0.009), without significant modification by eGFR. Conclusions In this large community-based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD.
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http://dx.doi.org/10.1161/JAHA.120.020646DOI Listing
September 2021

Changes in the gut microbiome influence the hypoglycemic effect of metformin through the altered metabolism of branched-chain and nonessential amino acids.

Diabetes Res Clin Pract 2021 Aug 27;178:108985. Epub 2021 Jul 27.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea. Electronic address:

Aims: Although metformin has been reported to affect the gut microbiome, the mechanism has not been fully determined. We explained the potential underlying mechanisms of metformin through a multiomics approach.

Methods: An open-label and single-arm clinical trial involving 20 healthy Korean was conducted. Serum glucose and insulin concentrations were measured, and stool samples were collected to analyze the microbiome. Untargeted metabolomic profiling of plasma, urine, and stool samples was performed by GC-TOF-MS. Network analysis was applied to infer the mechanism of the hypoglycemic effect of metformin.

Results: The relative abundances of Escherichia, Romboutsia, Intestinibacter, and Clostridium were changed by metformin treatment. Additionally, the relative abundances of metabolites, including carbohydrates, amino acids, and fatty acids, were changed. These changes were correlated with energy metabolism, gluconeogenesis, and branched-chain amino acid metabolism, which are major metabolic pathways related to the hypoglycemic effect.

Conclusions: We observed that specific changes in metabolites may affect hypoglycemic effects through both pathways related to AMPK activation and microbial changes. Energy metabolism was mainly related to hypoglycemic effects. In particular, branched-chain amino acid metabolism and gluconeogenesis were related to microbial metabolites. Our results will help uncover the potential underlying mechanisms of metformin through AMPK and the microbiome.
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http://dx.doi.org/10.1016/j.diabres.2021.108985DOI Listing
August 2021

Effects of chloroform fraction of Fritillariae Thunbergii Bulbus on atopic symptoms in a DNCB-induced atopic dermatitis-like skin lesion model and in vitro models.

J Ethnopharmacol 2021 Jul 24;281:114453. Epub 2021 Jul 24.

Department of Anatomy, College of Korean Medicine, Kyung Hee University, 26, Kyunghee dae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Fritillariae thunbergii Bulbus (FT), knowns as "Jeolpaemo ()" in Korean traditional medicine, is a perennial plant belonging to the Liliaceae family and has been used to treat symptoms such as cough, sputum formation, and purulent pneumonia. Owing to its effects of lowering heat, removing sputum, and reducing swelling, the plant has also been used as an external prescription medicine to treat inflammation.

Aim Of The Study: To analyze the anti-inflammatory effects of FT-ethanol extract (FT-Et) and FT-chloroform fraction extract (FT-Cl) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in vivo and in vitro.

Materials And Methods: The effect of FT-Et and FT-Cl on AD was observed using an AD-like skin lesion model induced by DNCB in vivo. HaCaT and RBL2H3 cells were used to determine the effects of FT-Et and FT-Cl in vitro. After inducing AD-like skin lesions in vivo, FT was topically applied to the skin lesion for 35 days. Epidermal thickness, dermal thickness, scratching behavior, infiltration of inflammatory cells, and expression of skin barrier proteins were measured. TARC, MDC, and IL-4 levels were analyzed using ELISA in HaCaT cells. Beta-hexosaminidase and IL-4 levels were measured in RBL2H3 cells. The expression of filaggrin (FLG), loricrin (LOR), involucrin (INV), and aquaporin-3(AQP-3) was measured by PCR. Phosphorylation of MAPKs was analyzed using Western blot technique.

Results: FT-Cl significantly reduced ear swelling, scratching behavior, SCORAD index, epidermal thickness, infiltration of inflammatory cells, and loss of skin barrier proteins. FT-Et inhibited the infiltration of mast cells and CD8 cells and decreased the loss of skin barrier proteins. In TNF-α/IFN-γ-stimulated HaCaT cells, FT-Cl inhibited TRAC, MDC, and IL-4 expression and upregulated the expression of FLG, INV, and AQP-3, whereas FT-Et inhibited the expression of TRAC and MDC and increased the expression of FLG, INV, and AQP-3 at high concentrations. In RBL2H3, FT-Cl downregulated β-hexosaminidase and IL-4 expression. In addition, FT-Cl inhibited the phosphorylation of ERK and p-38 in HaCaT and RBL2H3 cells.

Conclusions: Collectively, FT-Cl showed better effect than FT-Et in vivo and in vitro. These results suggest that a specific component present in FT-Cl acted against AD. Future research should focus on the analysis of components contained in FT-Cl and the anti-inflammatory effects of the active ingredient.
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http://dx.doi.org/10.1016/j.jep.2021.114453DOI Listing
July 2021

Matrix Effects on the Delivery Efficacy of Bifidobacterium animalis subsp. BB-12 on Fecal Microbiota, Gut Transit Time, and Short-Chain Fatty Acids in Healthy Young Adults.

mSphere 2021 Aug 7;6(4):e0008421. Epub 2021 Jul 7.

Department of Food Science, The Pennsylvania State Universitygrid.29857.31, University Park, Pennsylvania, USA.

Probiotics are consumed in fermented dairy products or as capsules for their putative health benefits. However, little research has been done to evaluate the effects of the delivery matrix on the health benefits of probiotics in humans. To examine the effects of delivering Bifidobacterium animalis subsp. BB-12 (BB-12) (log 10 ± 0.5 CFU/day) via a yogurt smoothie versus a capsule, we monitored the fecal microbiota, gut transit times (GTTs), and fecal excretion of short-chain fatty acids (SCFAs) in healthy adults. In a randomized, four-period, crossover study performed in a partially blind manner, 36 adults were recruited and randomly assigned to four treatments: control yogurt smoothie (YS), yogurt smoothie with BB-12 added prefermentation (PRE), yogurt smoothie with BB-12 added postfermentation (POST), and capsule containing BB-12 (CAP). Participants' fecal microbiota was assessed using 16S rRNA sequencing, GTTs via SmartPill, and fecal SCFAs by gas chromatography (GC) before (baseline) and after each intervention. Participants had significantly higher percentage of Streptococcus after consuming YS versus CAP ( = 0.01). -specific terminal restriction fragment length polymorphism analysis revealed a significantly higher percentage of B. animalis after consuming PRE and POST compared to baseline, YS, CAP, and final washout ( < 0.0001). The predominant SCFAs were negatively correlated with GTTs. Consumption of BB-12 delivered in a yogurt smoothie or capsule did not significantly alter the composition of the gut microbiota, GTTs, or fecal SCFA concentration of the study cohort. However, daily consumption of BB-12 in yogurt smoothie may result in higher relative abundance of in healthy adults. (This trial has been registered at ClinicalTrials.gov under identifier NCT01399996.) Bifidobacterium animalis subsp. BB-12 is a probiotic strain that has been used worldwide since 1985. It has commonly been delivered in fermented dairy products for perceived benefits associated with gut health and enhanced immune function. In addition to fermented dairy products, many new probiotic-containing alternatives such as probiotic-containing juice, probiotic-containing chocolate, and capsules have been developed. While these products provide more options for people to access probiotics, little research has been done on the effect of delivery matrix (dairy versus nondairy) on their efficacy in humans. In addition, it was unclear how yogurt fermentation may influence the survival of BB-12 in the product or on its performance The significance of our study is in simultaneously assessing the effect of BB-12, alone and in different delivery vehicles, on the gut transit time, fecal short-chain fatty acids, and the composition of the gut microbiota of the study cohort.
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http://dx.doi.org/10.1128/mSphere.00084-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386398PMC
August 2021

Effect of Adjuvant Chemotherapy on Elderly Stage II High-Risk Colorectal Cancer Patients.

Ann Coloproctol 2021 Jul 6. Epub 2021 Jul 6.

Department of General Surgery, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.

Purpose: Adjuvant chemotherapy (AC) is recommended for patients with stage II colorectal cancer with adverse features. However, the effect of adjuvant treatment in elderly patients with high-risk stage II colorectal cancer remains controversial. This study aimed to investigate the oncologic outcomes in elderly high-risk stage II colorectal cancer patients who underwent curative resection with or without AC.

Methods: Patients aged over 70 years having stage II colorectal adenocarcinoma with at least 1 adverse feature who underwent radical surgery between 2008 and 2017 at a single center were included. We compared recurrence-free survival (RFS) and overall survival (OS) between patients who received more than 80% of the planned AC cycle (the AC+ group) and those who did not receive it (the AC- group).

Results: The AC+ and AC- group contained 46 patients and 50 patients, respectively. The log-rank test revealed no significant intergroup differences in RFS (P = 0.083) and OS (P = 0.122). In the subgroup of 27 patients with more than 2 adverse features, the AC+ group (n = 16) showed better RFS (P = 0.006) and OS (P = 0.025) than the AC- group. In this subgroup, AC was the only significant factor affecting RFS in the multivariate analysis (P = 0.023). AC was significantly associated with OS (P = 0.033) in the univariate analysis, but not in the multivariate analysis (P = 0.332).

Conclusion: Among elderly patients with stage II high-risk colorectal cancer, the AC+ group did not show better RFS or OS than the AC- group. However, selected patients with more than 2 adverse features might benefit from AC.
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http://dx.doi.org/10.3393/ac.2020.00829.0118DOI Listing
July 2021

Increased incidence of unilateral sudden sensorineural hearing loss in patients with hematological malignancies requiring hematopoietic stem cell transplantation.

Clin Otolaryngol 2021 Jun 26. Epub 2021 Jun 26.

Department of Otorhinolaryngology, Yonsei University College of Medicine, Seodaemun-gu, Korea.

Haematopoietic stem cell transplantation (HSCT) may dramatically alter the immunity of a recipient. Transient immunodeficiency that occurs before and after HSCT could be associated with the development of sudden sensorineural hearing loss (SSNHL), which is presumed to be often due to viral aetiology. We found an incidence of SSNHL of 29.4 per 10,000 person-years in patients receiving HSCT, 12-fold higher than reported for background population incidence. Development of SSNHL tended to cluster early after diagnosis of haematological malignancies, rather than around date of treatment with HSCT. Increased risk of unilateral SSNHL in patients with haematological malignancy may relate to underlying disease rather than treatment.
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http://dx.doi.org/10.1111/coa.13829DOI Listing
June 2021

Prognostic Factors Affecting Disease-Free Survival and Overall Survival in T4 Colon Cancer.

Ann Coloproctol 2021 Aug 24;37(4):259-265. Epub 2021 Jun 24.

Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea.

Purpose: It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer.

Methods: Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS.

Results: Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS.

Conclusion: Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.
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http://dx.doi.org/10.3393/ac.2020.00759.0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391044PMC
August 2021

Scoring System for Differentiation of Complicated Appendicitis in Pediatric Patients: Appendicitis Scoring System in Children.

Glob Pediatr Health 2021 8;8:2333794X211022268. Epub 2021 Jun 8.

Department of General Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.

Although several scoring systems have been used to differentiate simple acute appendicitis from perforated appendicitis, no particular system has been widely accepted. Therefore, this study aimed to investigate preoperative factors associated with complicated appendicitis and to develop a scoring system that distinguishes complicated appendicitis in children aged <10 years. Patients aged <10 years who underwent surgical treatment for acute appendicitis between 2011 and 2019 were included in this study, after excluding those with insufficient medical records, with other diseases that affect the length of hospitalization, or without formal reports of abdominal computed tomography (CT) or ultrasonography (US). Complicated appendicitis was defined as hospitalization for ≥5 days postoperatively or readmission within 30 days postoperatively. Patient characteristics, symptoms, physical examination, laboratory data, and radiographic results were collected to determine predictors of complicated appendicitis. The mean age of 279 patients was 7.3 years. Among them, 57 patients had complicated appendicitis. A scoring system was developed based on the following 5 independent risk factors derived from multiple logistic regression analysis: body temperature, anorexia, diarrhea, C-reactive protein (CRP) level, and presence of periappendiceal free fluid on CT or US. The scoring system resulted in an area under the curve of .898 ( < .001). For patients aged <10 years, a new model that includes objective factors, such as body temperature, CRP levels, and radiography results, might help predict complicated appendicitis and determine treatment plans.
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http://dx.doi.org/10.1177/2333794X211022268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191077PMC
June 2021

Assessment of Oral Vancomycin-Induced Alterations in Gut Bacterial Microbiota and Metabolome of Healthy Men.

Front Cell Infect Microbiol 2021 27;11:629438. Epub 2021 May 27.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.

Several classes of antibiotics have reduced the mortality caused by infectious diseases; however, orally administered antibiotics alter the composition of gut microbiota, leading to dysbiosis-related disease. Therefore, in this study, we used 16S rRNA gene sequencing- and metabolomics-based approaches to investigate the effects of oral vancomycin on gut bacterial microbiota and the metabolome in biospecimens collected from healthy men. Samples collected from 11 healthy men were analyzed using 16S rRNA gene sequencing and metabolomics. 16S rRNA gene sequencing was performed to analyze the gut bacterial microbiota, and GC-TOFMS-based untargeted metabolomics was performed to analyze fecal, urine, and plasma metabolomics. Spearman's rank correlation was utilized to explore the associations between gut bacterial microbiota and metabolome. Fecal 16S rRNA gene sequencing analysis showed decreased relative abundance of genera belonging to the phyla Bacteroidetes and Firmicutes, and increased relative abundance of genera of the phyla Proteobacteria and Fusobacteria. Fecal metabolomics analysis showed that levels of uracil, L-aspartic acid, lithocholic acid, and deoxycholic acid were significantly higher at baseline, whereas that of dihydrouracil was significantly higher after vancomycin administration. No significant metabolic markers were selected from urine and plasma metabolomics analysis. This study demonstrates that oral vancomycin administration induces alterations in gut bacterial microbiota and metabolome. Correlation analysis between our two datasets shows that alteration of the gut bacterial microbiota, induced by oral vancomycin, potentially affected the systemic activity of dihydropyrimidine dehydrogenase. This correlation should be further examined in future studies to define the effects of gut bacterial microbiota on drug-metabolizing enzymes, thereby contributing to the development of personalized therapy.
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http://dx.doi.org/10.3389/fcimb.2021.629438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190408PMC
July 2021

Integrated Genomic Analyses of Cutaneous T Cell Lymphomas Reveal the Molecular Bases for Disease Heterogeneity.

Blood 2021 Jun 11. Epub 2021 Jun 11.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.

Cutaneous T cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled a cohort of CTCLs with representative samples from diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. 2 mutations have never been previously described for any cancer. Functionally, multiple mutations augment T cell receptor-dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways driving diverse disease phenotypes.
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http://dx.doi.org/10.1182/blood.2020009655DOI Listing
June 2021

Effect of tourniquet use on the risk of revision in total knee replacement surgery: an analysis of the National Joint Registry Data Set.

BMJ Open 2021 06 9;11(6):e045353. Epub 2021 Jun 9.

Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.

Objective: Tourniquet use in total knee replacement (TKR) is believed to improve the bone-cement interface by reducing bleeding, potentially prolonging implant survival. This study aimed to compare the risk of revision for primary cemented TKR performed with or without a tourniquet.

Design: We analysed data from the National Joint Registry (NJR) for all primary cemented TKRs performed in England and Wales between April 2003 and December 2003. Kaplan-Meier plots and Cox regression were used to assess the influence of tourniquet use, age at time of surgery, sex and American Society of Anaesthesiologists (ASA) classification on risk of revision for all-causes.

Results: Data were available for 16 974 cases of primary cemented TKR, of which 16 132 had surgery with a tourniquet and 842 had surgery without a tourniquet. At 10 years, 3.8% had undergone revision (95% CI 2.6% to 5.5%) in the no-tourniquet group and 3.1% in the tourniquet group (95% CI 2.8% to 3.4%). After adjusting for age at primary surgery, gender and primary ASA score, the HR for all-cause revision for cemented TKR without a tourniquet was 0.82 (95% CI 0.57 to 1.18).

Conclusions: We did not find evidence that using a tourniquet for primary cemented TKR offers a clinically important or statistically significant reduction in the risk of all-cause revision up to 13 years after surgery. Surgeons should consider this evidence when deciding whether to use a tourniquet for cemented TKR.
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http://dx.doi.org/10.1136/bmjopen-2020-045353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191625PMC
June 2021

A comparison on health-related lifestyle, dietary habits, and depression by exercise frequency of college students.

Nutr Res Pract 2021 Jun 12;15(3):355-366. Epub 2021 Apr 12.

Department of Food and Nutrition, Myongji University, Yongin 17058, Korea.

Background/objectives: The study was performed to investigate health-related lifestyle, dietary habits, and depression according to exercise frequency to understand complex factors that affect effective health management. Thus, exercise frequency, health-related lifestyle, dietary habits, and depression were evaluated in college students in Seoul and Gyeonggi-do areas.

Subjects/methods: A survey was conducted on college students, aged 19-29, in Seoul and Gyeonggi-do areas from May 13 to May 31, 2020. A total of 594 questionnaires were collected and 566 (269 from males, 297 from females) were statistically analyzed, except 28 with incomplete responses. Collected data were analyzed using SPSS WIN 21.0 program.

Results: The sex distribution of the 3 groups according to exercise frequency was significantly different; the ratio of males in over 3 times/week group was significantly higher than those in 1-2 times/week group and no-exercise group ( < 0.001). The height ( < 0.001), weight ( < 0.001), and body mass index ( < 0.05) were significantly higher in over 3 times/week group compared to no-exercise group. The ratio of subjects who answered 'good' or 'very good' for subjective health condition was significantly high in the order of 'over 3 times/week' group (59.1%), '1-2 times/week' group (34.5%), and 'no-exercise' group (25.0%) ( < 0.001). The ratio for meal regularity was high as 56.6% in 'over 3 times/week' group and the ratio for irregular meals was significantly higher in 'no-exercise' group (67.2%) and '1-2 times/week' group (54.9%) ( < 0.001). Among questions on dietary habits, 'Eat meat, fish, egg or beans' ( < 0.01) and 'Eat fruit' ( < 0.01) were significantly higher in 'over 3 times/week' group compared to 'no-exercise' group. 'Drink more than 2 liters of water' ( < 0.001) was 0.70 in 'over 3 times/week' group, which was significantly higher than 0.54 in '1-2 times/week' group and 0.38 in 'no-exercise' group. Moderate depression and severe depression that need treatments were significantly lower in 'over 3 times/week' group (18.7%) compared to '1-2 times/week' group (26.0%) and 'no-exercise' group (29.7%) ( < 0.05).

Conclusions: It is considered that combined intervention for exercise habits, proper dietary habits, and depression management is needed for effective health management.
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http://dx.doi.org/10.4162/nrp.2021.15.3.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155223PMC
June 2021

Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S Containing Triple Mutations.

Biomol Ther (Seoul) 2021 Jun 2. Epub 2021 Jun 2.

Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wildtype EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and thirdgeneration EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/ T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.
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http://dx.doi.org/10.4062/biomolther.2021.047DOI Listing
June 2021

Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue.

Nat Biomed Eng 2021 07 27;5(7):759-771. Epub 2021 May 27.

Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders.
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http://dx.doi.org/10.1038/s41551-021-00723-yDOI Listing
July 2021

Investigation of colorimetric biosensor array based on programable surface chemistry of M13 bacteriophage towards artificial nose for volatile organic compound detection: From basic properties of the biosensor to practical application.

Biosens Bioelectron 2021 Sep 16;188:113339. Epub 2021 May 16.

Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 46241, Republic of Korea; Department of Nano Fusion Technology, Pusan National University, Busan, 46241, Republic of Korea; Department of Nanoenergy Engineering, Pusan National University, Busan, 46241, Republic of Korea. Electronic address:

Various threats such as explosives, drugs, environmental hormones, and spoiled food manifest themselves with the presence of volatile organic compounds (VOCs) in our environment. In order to recognize and respond to these threats early, the demand for highly sensitive and selective electronic noses is increasing. The M13 bacteriophage-based optoelectronic nose is an excellent candidate to meet all these requirements. However, the phage-based electronic nose is still in its infancy, and strategies that include a systematic approach and development are still essential. Here, we have integrated theoretical and experimental approaches to analyze the correlation between the surface chemistry of genetically engineered phage and the phage-based optoelectronic nose properties. The reactivity of the genetically engineered phage color film to some VOCs were quantitatively analyzed, and the correlation with the binding affinity value calculated by Density-functional theory (DFT) was compared. This demonstrates that phage color films have controllable reactivity through a genetic engineering. We have selected phages that are advantageous in distinguishing each VOCs in this work through hierarchical cluster analysis (HCA). The reason for this difference was verified through the optimized geometry calculated by DFT. Through this, it was confirmed that the tryptophan-based and the Histidine-based of genetically engineered phage film are important in distinguishing the VOCs (Y-hexanolactone, 2-isopropyl-4-methylthiazole, ethanol, acetone, ethyl acetate, and acetaldehyde) used in this work to evaluate the peach freshness quality. This was applied to the design of a field-applied phage-based optoelectronic nose and verified by measuring the freshness of the actual fruit.
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http://dx.doi.org/10.1016/j.bios.2021.113339DOI Listing
September 2021

Trends in junk food consumption among US children and adults, 2001-2018.

Am J Clin Nutr 2021 09;114(3):1039-1048

Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.

Background: Trends in junk food consumption, a risk for obesity, are not well established.

Objectives: We examined national trends in types of junk food (excluding beverages) and their sources (grocery, restaurants, schools, etc.), overall and in population subgroups.

Methods: We assessed 29,970 children (aged 2-19 y) and 44,501 adults (aged ≥20 y) with 24-h dietary recall data from 9 NHANES cycles (2001-2002 to 2017-2018). Trends in junk food were assessed over time using 1-d values for individuals with single recalls and 2-d means for others.

Results: From 2001 to 2018, percent energy (%E) from junk food remained stable for children (from 18.1% to 17.5%, P-trend = 0.25) and decreased for adults (14.1% to 13.0%, P-trend = 0.002). Among children, increases occurred in %E from crackers (1.19% to 1.35%) and snack/meal bars (0.38% to 0.69%) and decreases in candy (2.58% to 1.96%) and other desserts (3.11% to 2.48%) (all P-trends < 0.01). Among adults, increases occurred in snack/meal bars (0.31% to 0.78%, P-trend < 0.001) and decreases in candy (1.97% to 1.55%; P-trend < 0.001), sweet bakery products (5.52% to 4.98%; P-trend = 0.04), and other desserts (2.19% to 1.86%; P-trend = 0.001). In 2017-2018, grocery stores provided the largest proportion of junk food (72.7% for children, 77.1% for adults), followed by other sources (13.1%, 12.1%), restaurants (8.05%, 9.11%), schools (4.86%), and worksites (1.99%). In both children and adults, junk food intake was higher among non-Hispanic white and black Americans compared with Mexican Americans, among those with higher compared with lower education, among women compared with men, and among older compared with younger adults. In sensitivity analyses using only 1-d recalls, mean junk food intake each cycle was ∼0.8-1.0 and 0.3-0.4%E units higher in children and adults, respectively, with otherwise similar trends and subgroup differences over time.

Conclusions: From 2001 to 2018, %E from junk food represented nearly 1 in 5 calories among children, without change, and nearly 1 in 7 calories, with modest decrease, among adults, with disparities in subgroups.
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http://dx.doi.org/10.1093/ajcn/nqab129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408879PMC
September 2021

Effects of vancomycin-induced gut microbiome alteration on the pharmacodynamics of metformin in healthy male subjects.

Clin Transl Sci 2021 May 13. Epub 2021 May 13.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, South Korea.

Metformin is a major treatment for type 2 diabetes. This study was conducted to investigate the impact of gut microbiome dysbiosis on the pharmacokinetics and antihyperglycemic effects of metformin. Healthy adult males aged 19-45 years with no defecation abnormalities were recruited for this 4-period clinical study: baseline; post-metformin (i.e., multiple oral doses of 1000 mg metformin on days 1-4); post-vancomycin (i.e., multiple oral doses of 500 mg vancomycin on days 11-17 inducing gut microbiome changes); and post-metformin + vancomycin (i.e., multiple oral doses of 1000 mg metformin on days 16-19). In each period, serum glucose and insulin concentrations following an oral glucose tolerance test, fecal samples for gut microbiome composition, and safety data were obtained. Following metformin dosing, plasma and urine samples for pharmacokinetics were collected. Nine subjects completed the study. The pharmacokinetics of metformin remained unchanged, and the antihyperglycemic effect was significantly decreased after vancomycin administration (p value = 0.039), demonstrating the weak relationship between the pharmacokinetics and pharmacodynamics of metformin. Relative abundances of some genus were changed after vancomycin administration, and tended to correlate with the antihyperglycemic effects of metformin (p value = 0.062 for Erysipelatoclostridium; p value = 0.039 for Enterobacter; and p value = 0.086 for Faecalibacterium). Adverse events occurred in all subjects and were resolved without sequelae. In conclusion, a decrease in the antihyperglycemic effect of metformin was observed after concomitant administration with vancomycin, without changes in metformin pharmacokinetics. The antihyperglycemic effect was tended to correlate with the relative abundance of several genus, suggesting that the effect of metformin is partly attributable to the gut microbiome (ClinicalTrials.gov, NCT03809260).
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http://dx.doi.org/10.1111/cts.13051DOI Listing
May 2021

Association between stress and dietary habits, emotional eating behavior and insomnia of middle-aged men and women in Seoul and Gyeonggi.

Nutr Res Pract 2021 Apr 8;15(2):225-234. Epub 2021 Mar 8.

Department of Food and Nutrition, Myongji University, Yongin 17058, Korea.

Background/objectives: The study was performed to investigate the degree of perceived stress by sex in middle-aged people, and to provide basic data for appropriate nutrition education and interventional measures for middle-aged subjects through comparative analysis of association between stress and dietary habits, emotional eating behavior, and insomnia.

Subjects/methods: A survey was conducted in 670 middle-aged subjects (320 men and 350 women) aged 40-64 years, resided in Seoul and Gyeonggi area. Collected data were analyzed using SPSS WIN 25.0 program.

Results: Perceived stress in middle-aged subjects was not different by sex. Stress was higher in men with low dietary habits level compared to other groups ( < 0.001), and was higher in women with low and moderate dietary habits level compared to women with high dietary habits level ( < 0.05). Stress in men was higher in the group with emotional eaters ( < 0.05), and the same result was shown in women ( < 0.001). Stress was higher in both men and women with poor sleep quality ( < 0.001). Stress score was positively correlated with emotional dietary behavior and insomnia ( < 0.001) and negatively correlated with dietary habits ( < 0.001).

Conclusions: It is considered that proper nutrition education and interventional measures according to sex are needed for stress control and proper dietary behavior and lifestyle in middle-aged people population, along with projects and policies at the national level.
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http://dx.doi.org/10.4162/nrp.2021.15.2.225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007409PMC
April 2021

pH-Responsive Amphiphilic Polyether Micelles with Superior Stability for Smart Drug Delivery.

Biomacromolecules 2021 05 9;22(5):2043-2056. Epub 2021 Apr 9.

Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.

Despite widespread interest in the amphiphilic polymeric micelles for drug delivery systems, it is highly desirable to achieve high loading capacity and high efficiency to reduce the side effects of therapeutic agents while maximizing their efficacy. Here, we present a novel hydrophobic epoxide monomer, cyclohexyloxy ethyl glycidyl ether (CHGE), containing an acetal group as a pH-responsive cleavable linkage. A series of its homopolymers, poly(cyclohexyloxy ethyl glycidyl ether)s (PCHGEs), and block copolymers, poly(ethylene glycol)--poly(cyclohexyloxy ethyl glycidyl ether)s (PEG--PCHGE), were synthesized via anionic ring-opening polymerization in a controlled manner. Subsequently, the self-assembled polymeric micelles of PEG--PCHGE demonstrated high loading capacity, excellent stability in biological media, tunable release efficiency, and high cell viability. Importantly, quantum mechanical calculations performed by considering prolonged hydrolysis of the acetal group in CHGE indicated that the CHGE monomer had higher hydrophobicity than three other functional epoxide monomer analogues developed. Furthermore, the preferential cellular uptake and therapeutic efficacy confirmed the enhanced stability and the pH-responsive degradation of the amphiphilic block copolymer micelles. This study provides a new platform for the development of versatile smart polymeric drug delivery systems with high loading efficiency and tailorable release profiles.
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http://dx.doi.org/10.1021/acs.biomac.1c00163DOI Listing
May 2021

Polyvictimization Risk Among North Korean Refugee Women in South Korea.

J Interpers Violence 2021 Apr 9:8862605211005146. Epub 2021 Apr 9.

University of Michigan, Ann Arbor, MI, USA.

North Korean (NK) refugee women living in South Korea are known to be vulnerable to interpersonal violence, but little is known about the possible link between or co-occurrence of acts of sexual violence (SV) and intimate partner violence (IPV) perpetrated against NK refugee women. This study examined the prevalence of polyvictimization and explored the association between SV in different settings (i.e., North Korea, intermediate countries, and South Korea) and various types of IPV. A convenience sample of 140 adult NK refugee women was analyzed, and logistic regression analyses were conducted to examine the link between SV and polyvictimization in IPV. NK refugee women with a history of SV reported a significantly higher rate of IPV over the previous 12 months (51.2%) compared to those without a history of SV (20.4%). NK refugee women with a history of SV are significantly more likely to become victims of most forms of IPV. SV victimization in intermediate countries significantly increased the odds of being physically victimized by their male partners in South Korea ( = 3.31, =.05). An SV victimization history in North Korea ( = 4.50, =.04) and SV victimization experienced outside their intimate relationship in South Korea significantly increased the odds of sexual IPV from their current intimate partner ( = 4.74, =.03). This study showed that victims of human trafficking and sexual assault during their journey to South Korea were at a greater risk of IPV in South Korea. Male partners of NK refugee women with a history of SV may shame and physically sanction NK refugee women for "breaching honor." Therefore, screening for potential risk of physical and sexual IPV among NK refugee women with a prior exposure to SV is needed to develop programs in safety planning for NK refugee women experiencing SV and IPV.
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http://dx.doi.org/10.1177/08862605211005146DOI Listing
April 2021

Hydrogen Barriers Based on Chemical Trapping Using Chemically Modulated AlO Grown by Atomic Layer Deposition for InGaZnO Thin-Film Transistors.

ACS Appl Mater Interfaces 2021 May 5;13(17):20349-20360. Epub 2021 Apr 5.

School of Electrical and Electronics Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

In this study, the excellent hydrogen barrier properties of the atomic-layer-deposition-grown AlO (ALD AlO) are first reported for improving the stability of amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs). Chemical species in AlO were artificially modulated during the ALD process using different oxidants, such as HO and O (HO-AlO and O-AlO, respectively). When hydrogen was incorporated into the HO-AlO-passivated TFT, a large negative shift in (ca. -12 V) was observed. In contrast, when hydrogen was incorporated into the O-AlO-passivated TFT, there was a negligible shift in (ca. -0.66 V), which indicates that the O-AlO has a remarkable hydrogen barrier property. We presented a mechanism for trapping hydrogen in a O-AlO via various chemical and electrical analyses and revealed that hydrogen molecules were trapped by C-O bonds in the O-AlO, preventing the inflow of hydrogen to the a-IGZO. Additionally, to minimize the deterioration of the pristine device that occurs after a barrier deposition, a bi-layered hydrogen barrier by stacking HO- and O-AlO is adopted. Such a barrier can provide ultrastable performance without degradation. Therefore, we envisioned that the excellent hydrogen barrier suggested in this paper can provide the possibility of improving the stability of devices in various fields by effectively blocking hydrogen inflows.
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http://dx.doi.org/10.1021/acsami.1c02597DOI Listing
May 2021

Acute Liver Failure Secondary to Hepatic Infiltration of Malignant Melanoma: A Case Report.

Clin Endosc 2021 Apr 1. Epub 2021 Apr 1.

Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea.

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.
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http://dx.doi.org/10.5946/ce.2020.272DOI Listing
April 2021

Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop.

J Cell Biol 2021 05;220(5)

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. In contrast, p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunity, is only partially required for this rejuvenated immunity. The up-regulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn down-regulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS prevents immune aging via the up-regulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a feedforward mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies against immune aging in humans.
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http://dx.doi.org/10.1083/jcb.202006174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941181PMC
May 2021

The potential pathways underlying the association of propyl-paraben exposure with aeroallergen sensitization and EASI score using metabolomics analysis.

Sci Rep 2021 Feb 12;11(1):3772. Epub 2021 Feb 12.

Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyonggi-do, 13496, Republic of Korea.

Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, D-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.
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http://dx.doi.org/10.1038/s41598-021-83288-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881090PMC
February 2021

Optical bioelectronic nose of outstanding sensitivity and selectivity toward volatile organic compounds implemented with genetically engineered bacteriophage: Integrated study of multi-scale computational prediction and experimental validation.

Biosens Bioelectron 2021 Apr 13;177:112979. Epub 2021 Jan 13.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Republic of Korea. Electronic address:

Genetic engineering of a bacteriophage is a promising way to develop a highly functional biosensor. Almost countless configurational degree of freedom in the manipulation, considerable uncertainty and cost involved with the approach, however, have been huddles for the objective. In this paper, we demonstrate rapidly responding optical biosensor with high selectivity toward gaseous explosives with genetically engineered phages. The sensors are equipped with peptide sequences in phages optimally interacting with the volatile organic compounds (VOCs) in visible light regime. To overcome the conventional issues, we use extensive utilization of empirical calculations to construct a large database of 8000 tripeptides and screen the best for electronic nose sensing performance toward nine VOCs belonging to three chemical classes. First-principles density functional theory (DFT) calculations unveil underlying correlations between the chemical affinity and optical property change on an electronic band structure level. The computational outcomes are validated by in vitro experimental design and testing of multiarray sensors using genetically modified phage implemented with five selected tripeptide sequences and wild-type phages. The classification success rates estimated from hierarchical cluster analysis are shown to be very consistent with the calculations. Our optical biosensor demonstrates a 1 ppb level of sensing resolution for explosive VOCs, which is a substantial improvement over conventional biosensor. The systematic interplay of big data-based computational prediction and in situ experimental validation can provide smart design principles for unconventionally outstanding biosensors.
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http://dx.doi.org/10.1016/j.bios.2021.112979DOI Listing
April 2021

Development of a zebrafish screening model for diabetic retinopathy induced by hyperglycemia: Reproducibility verification in animal model.

Biomed Pharmacother 2021 Mar 1;135:111201. Epub 2021 Feb 1.

Inje University Busan Paik Hospital, Department of Ophthalmology. 81, Jinsa-ro 83beon-gil, Busanjin-gu, Busan, South Korea; EYEBIOKOREA, 81, Jinsa-ro 83beon-gil, Busanjin-gu, Busan, South Korea. Electronic address:

This study aimed at creating a zebrafish screening model for diabetic retinopathy, and evaluated the effects of aflibercept, which is being used to treated diabetic retinopathy. A morphological change occurred at 160 mM of glucose. The survival and hatching rate decreased in a dose-dependent manner. In the 130 mM glucose group, the retinal vessel diameter was more than double that in the normal group. The zebrafish embryo morphology changed in 200 μg/mL and 400 μg/mL at aflibercept. The survival and hatching rate decrease at 400 μg/mL. Aflibercept 100 μg/mL was a nontoxic and effective dose for the zebrafish diabetic retinopathy model. The expression of diabetic retinopathy inflammatory markers was increased in hyperglycemia. But the inflammation was improved by aflibercept in the zebrafish eye. In a zebrafish diabetic retinopathy model, the diameters of retinal vessels were reduced after treatment with aflibercept, and molecular biological and histopathological efficacy was confirmed. This model can serve for screening of new drug candidates for treatment of in diabetic retinopathy.
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http://dx.doi.org/10.1016/j.biopha.2020.111201DOI Listing
March 2021
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