Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel.

Mechanically activating (MA) channels transduce numerous physiological functions. Tentonin 3/TMEM150C (TTN3) confers MA currents with slow inactivation kinetics in somato- and barosensory neurons. However, questions were raised about its role as a Piezo1 regulator and its potential as a channel pore. Here, we demonstrate that purified TTN3 proteins incorporated into the lipid bilayer displayed spontaneous and pressure-sensitive channel currents. These MA currents were conserved across vertebrates and differ from Piezo1 in activation threshold and pharmacological response. Deep neural network structure prediction programs coupled with mutagenetic analysis predicted a rectangular-shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit center. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These findings suggest that TTN3 is a pore-forming subunit of a distinct slow inactivation MA channel, potentially possessing a tetrameric structure.

Patterns of cigarette, heated tobacco product, and nicotine vaping product use among Korean adults: Findings from the 2020 ITC Korea Survey.

INTRODUCTION: Non-combustible nicotine products (NCNPs), such as heated tobacco products (HTPs) and nicotine vaping products (NVPs) have gained a significant nicotine market share in South Korea. This descriptive study examined patterns of regular cigarette and NCNP use among South Korean adults. METHODS: Data were from the 2020 International Tobacco Control Korea Survey and included 4016 adults (aged ≥19 years) in the Republic of Korea who were regularly (at least weekly) using at least one NCNP (NVP/HTP, n=2117) and/or smoked cigarettes (n=3763) at the time of the survey. Weighted descriptive estimates were computed to assess respondents' nicotine product use among all respondents (exclusive, dual, or triple use). Thereafter, we identified sociodemographic characteristics associated with NCNP use (n=2117). RESULTS: Among Korean adults who were smoking cigarettes, 83.1% (95% CI: 81.6-84.6) did so exclusively, and 16.9% (95% CI: 15.4-18.4) smoked cigarettes and used NCNPs. Among those who used HTPs (n=1877), 14.9% (95% CI: 11.5-18.4) did so exclusively, 59.6% used HTPs and smoked cigarettes (95% CI: 55.4-63.1), 4.2% used HTPs and vaped (95% CI: 11.5-18.4), and 21.6% (95% CI: 18.9-24.2) used all three products. Of adults who used HTPs and smoked cigarettes, 86.6% smoked daily. Among those who vaped (n=865), 13.3% did so exclusively (95% CI: 9.4-17.1), 55.6% (95% CI: 49.6-61.5) vaped and smoked cigarettes, 5.1% (95% CI: 1.7-8.6) used HTPs and vaped, and 26.1% (95% CI: 22.1-30.1) used all three products. Of adults who vaped and smoked cigarettes, 82.4% (95% CI: 77.1-87.7) smoked daily. CONCLUSIONS: Cigarettes remain the most commonly used nicotine product in South Korea, and among adults using heated tobacco and/or vaping products, the majority were also smoking. Research is urgently needed to assess whether adults who are using an NCNP are doing so to quit, or rather to complement their cigarette smoking.

Public support for tobacco endgame policies in South Korea: Findings from the 2020 International Tobacco Control Korea Survey.

BACKGROUND: Strong public support can increase the likelihood of adopting tobacco control policies. We assessed support for six commercial tobacco endgame policies in South Korea: limiting the nicotine in cigarettes, banning all additives in cigarettes, restricting the number of places where cigarettes are sold, and banning the manufacture and sales of cigarettes (unconditionally, with the provision of cessation support and with alternative tobacco products available). METHODS: Data were obtained from 4740 adults who completed the 2020 International Tobacco Control Korea Survey. Participants were categorised based on their nicotine use: (1) did not use any products, (2) vaped and/or used heated tobacco products (HTPs) but did not smoke cigarettes, (3) smoked cigarettes only and (4) smoked cigarettes and vaped and/or used HTPs. Attitudes towards the policies were classified as supportive, undecided or opposed. Weighted multinomial logistic regression models assessed support levels according to nicotine use. RESULTS: Support was highest for limiting the nicotine content in cigarettes (68.4%; 95% CI 64.6% to 72.3%) and restricting the number of retailers (68.1%; 95% CI 64.5% to 71.7%), and lowest for banning cigarette sales if alternative products are made available (45.0%; 95% CI 40.9% to 49.1%). People who did not use any products were most likely to support endgame policies, except for banning cigarette sales with alternatives available. The proportion of undecided participants exceeded 10% (range 13%-25%) for all policies. CONCLUSION: There is a strong public support for tobacco endgame policies in South Korea. Further research should prioritise the development of strategies to ensure the effective implementation of highly supported policies.

Perceptions of harmfulness of heated tobacco and nicotine vaping products compared to cigarettes, and the association of advertising exposure on harm perceptions among adults who smoke in South Korea: Cross-sectional findings from the 2020 ITC Korea Survey.

INTRODUCTION: Heated tobacco products (HTPs) and nicotine vaping products (NVPs) both are legal consumer products in the Republic of Korea. Little is known about perceptions of harmfulness of HTPs and NVPs relative to cigarettes in South Korea among adults who smoke, and how exposure to marketing may be associated with harmfulness perceptions. METHODS: This study used data from the 2020 International Tobacco Control (ITC) Korea Survey, and included 3713 adult (aged 19 years) cigarette smokers who were: 1) exclusive smokers (n=1845); 2) dual HTP + cigarette consumers (n=1130); 3) dual NVP + cigarette consumers (n=224); and 4) triple consumers (all three products, n=514). Weighted multinomial regression models were conducted to estimate smokers' perceptions of harmfulness of HTPs and NVPs compared to cigarettes, NVPs to HTPs, and self-reported exposure to HTP/NVP advertising. Analyses compared the perceptions of harmfulness between the four different consumer groups, and tested whether exposure to HTP/NVP advertising was associated with perceptions of lower relative harm. RESULTS: Among all respondents, 27.5% believe that HTPs are less harmful than cigarettes and 23.4% believe that NVPs are less harmful than cigarettes. Exclusive cigarettes smokers were significantly less likely to perceive that HTPs and NVPs are less harmful than cigarettes compared to dual HTP + cigarette consumers, dual NVP + cigarette consumers, and triple consumers (all p<0.001). Half of respondents perceive NVPs as equally harmful as HTPs (14.1% perceive NVPs as more harmful than HTPs). Exposure to HTP/NVP advertising was associated with perceiving these products as less harmful than cigarettes. CONCLUSIONS: About one-quarter of Korean cigarette smokers perceive HTPs and NVPs as less harmful than cigarettes. Further investigation is required to understand how harm perceptions and HTP/NVP advertising are related to changes in product use, such as switching between products, using multiple products, or discontinuing all product use.

Reasons for Initiation and Regular Use of Heated Tobacco Products among Current and Former Smokers in South Korea: Findings from the 2020 ITC Korea Survey.

South Korea is the world's second-largest heated tobacco product (HTP) market after Japan. HTP sales in South Korea have increased rapidly since May 2017, accounting for 10.6% of the total tobacco market in 2020. Despite this, little is known as to why HTP consumers who were current and former smokers started using HTPs and used them regularly. We analyzed cross-sectional data for 1815 adults (aged 19+) who participated in the 2020 International Tobacco Control (ITC) Korea Survey, of whom 1650 were HTP-cigarette consumers (those who reported smoking cigarettes and using HTPs ≥ weekly) and 165 were exclusive HTP consumers (using HTPs ≥ weekly) who were former or occasional smokers (smoking cigarette < weekly). Respondents were asked to report the reason(s) they used HTPs, with 25 possible reasons for HTP-cigarette consumers and 22 for exclusive HTP consumers. The most common reasons for initiating HTP use among all HTP consumers were out of curiosity (58.9%), family and friends use HTPs (45.5%), and they like the HTP technology (35.9%). The most common reasons for regularly using HTPs among all HTP consumers were that they were less smelly than cigarettes (71.3%), HTPs are less harmful to own health than cigarettes (48.6%), and stress reduction (47.4%). Overall, 35.4% of HTP-cigarette consumers reported using HTPs to quit smoking, 14.7% to reduce smoking but not to quit, and 49.7% for other reasons besides quitting or reducing smoking. In conclusion, several common reasons for initiating and regularly using HTPs were endorsed by all HTP consumers who were smoking, had quit smoking completely, or occasionally smoked. Notably, only about one-third of HTP-cigarette consumers said they were using HTPs to quit smoking, suggesting that most had no intention of using HTPs as an aid to quit smoking in South Korea.

Apoptosis-Inducing Effects of Short-Chain Fatty Acids-Rich Fermented Pistachio Milk in Human Colon Carcinoma Cells.

Pistachio milk (PM), an extraction product of pistachio, is protein- and fat-dense food. Short-chain fatty acids (SCFAs) are known for inducing cytotoxicity and apoptosis in colon carcinoma cells. This study aimed to find an optimal combination of probiotics that can produce a higher amount of SCFAs in PM. In addition, the anti-cancer effect of fermented PM on human colon carcinoma cells (Caco-2) was determined. The combinations of probiotics were as follows: Streptococcus thermophilus + Lactobacillus bulgaricus (C); C + Lactobacillus acidophilus (C-La); C + Lactobacillus gasseri (C-Lg); C + Bifidobacterium bifidum (C-Bb). The results indicated that fermented PM was produced after a short fermentation time in all the probiotics combinations. C-Bb produced up to 1.5-fold more acetate than the other probiotics combinations did. A significant amount of cytotoxicity, i.e., 78, 56, and 29% cell viability was observed in Caco-2 cells by C-Bb-fermented PM at 1, 2.5 and 5%, respectively. C-Bb-fermented PM (5%) induced early and late apoptosis up to 6-fold. Additionally, Caco-2 cells treated with C-Bb-fermented PM significantly induced the downregulation of α-tubulin and the upregulation of cleaved caspase-3, as well as nuclear condensation and fragmentation. Our data suggest that fermented PM, which is rich in acetate, may have the potential as a functional food possessing anti-colon cancer properties.

Daphne genkwa flower extract promotes the neuroprotective effects of microglia.

BACKGROUND: Microglia are innate immune cells in the central nervous system that play a crucial role in neuroprotection by releasing neurotrophic factors, removing pathogens through phagocytosis, and regulating brain homeostasis. The constituents extracted from the roots and stems of the Daphne genkwa plant have shown neuroprotective effects in an animal model of Parkinson's disease. However, the effect of Daphne genkwa plant extract on microglia has yet to be demonstrated. PURPOSE: To study the anti-inflammatory and neuroprotective effects of Daphne genkwa flower extract (GFE) in microglia and explore the underlying mechanisms. METHODS: In-vitro mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase, Arginase1, and brain derived neurotropic factor (BDNF) were analyzed by reverse transcription polymerase chain reaction in microglia cells. Nitric oxide (NO) and TNF-α protein were respectively analyzed by Griess reagent and Enzyme Linked Immunosorbent Assay. Immunoreactivity of Iba-1, Neu-N, and BDNF in mouse brain were analyzed by immunofluorescence staining. Phagocytosis capacity of microglia was examined using fluorescent zymosan-red particles. RESULTS: GFE significantly inhibited lipopolysaccharide (LPS)-induced neuroinflammation and promoted neuroprotection both in vitro and in vivo. First, GFE inhibited the LPS-induced inflammatory factors NO, iNOS, and TNF-α in microglial cell lines and primary glial cells, thus demonstrating anti-inflammatory effects. Arginase1 and BDNF mRNA levels were increased in primary glial cells treated with GFE. Phagocytosis was also increased in microglia treated with GFE, suggesting a neuroprotective effect of GFE. In vivo, neuroprotective and anti-neuroinflammatory effects of GFE were also found in the mouse brain, as oral administration of GFE significantly inhibited LPS-induced neuronal loss and inflammatory activation of microglia. CONCLUSION: GFE has anti-inflammatory effects and promotes microglial neuroprotective effects. GFE inhibited the pro-inflammatory mediators and enhanced neuroprotective microglia activity by increasing BDNF expression and phagocytosis. These novel findings of the GFE effect on microglia show an innovative approach that can potentially promote neuroprotection for the prevention of neurodegenerative diseases.

SNA077, an Extract of Marine Streptomyces sp., Inhibits Melanogenesis by Downregulating Melanogenic Proteins via Inactivation of cAMP/PKA/CREB Signaling.

Excess melanin in skin is known to be the main cause of hyper-pigmentary skin diseases such as freckles and lentigo. This study aimed to evaluate the depigmenting efficacy of an extract from the marine microorganism strain, Streptomyces sp. SNA077. To determine the anti-melanogenic efficacy of SNA077, we assessed the melanin contents of SNA077-treated B16, Melan-a, and MNT-1 cells. We observed the expression of key enzymes in melanogenesis via qRT-PCR and Western blot analyses. We further estimated the skin-whitening effect of SNA077 using a skin-equivalent model. SNA077 dramatically decreased the melanin production of B16 cells, Melan-a, and MNT-1 cells. In B16 cells treated with SNA077, the activity of cellular tyrosinase was clearly inhibited. In addition, the mRNA and protein expression levels of melanogenic genes were suppressed by SNA077 treatment in B16 and MNT-1 cells. Upstream of tyrosinase, the expression levels of phospho-CREB, phospho-p38, PKA activity, cyclic AMP production, and MC1R gene expression were inhibited by SNA077. Finally, SNA077 clearly showed a skin-brightening effect with a reduced melanin content in the skin tissue model. Collectively, our results suggest for the first time that an extract of marine Streptomyces sp. SNA077 could be a novel anti-melanogenic material for skin whitening.

Amplification of olfactory signals by Anoctamin 9 is important for mammalian olfaction.

Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Thus, we concluded that the signal amplification by ANO9 is important for mammalian olfactory transduction.

Factors Associated with Quit Intentions among Adult Smokers in South Korea: Findings from the 2020 ITC Korea Survey.

Background: South Korea has made substantial progress on tobacco control, but cigarette smoking prevalence is still high. Previous studies were conducted before the use of nicotine vaping products (NVPs) or heated tobacco products (HTPs) became popular. Thus, whether the concurrent use of NVPs or HTPs affects quit intentions among Korean smokers remains a question that needs to be explored. This study aims to identify predictors of quit intentions among cigarette-only smokers and concurrent users of cigarettes and NVPs or HTPs. Methods: Data were from the 2020 International Tobacco Control Korea Survey. Included in the analysis were 3778 adult cigarette smokers: 1900 at-least-weekly exclusive smokers and 1878 at-least-weekly concurrent smokers and HTP or NVP users. Bivariate and multivariable logistic regression analyses were conducted. Results: Quit intentions were reported by 66.4% of respondents. Factors significantly associated with quit intentions included younger age, having a spouse/partner, lower nicotine dependence, reporting a past quit attempt, regretting starting smoking, believing that smoking had damaged health, worrying that smoking will damage future health, and perceiving health benefits of quitting. Current use of NVPs or HTPs was not significantly associated with quit intentions. Conclusions: This study contributes the following to current literature: intrinsic health-related beliefs were more important than societal norms in shaping quit intentions. These findings should be considered in shaping future smoking cessation policies, such as reinforcing education programs that emphasize the benefits of quitting for personal health reasons, lowering nicotine dependence, and encouraging multiple quit attempts and successful quitting.

In vitro and in vivo anti-tumor efficacy of krill oil against bladder cancer: Involvement of tumor-associated angiogenic vasculature.

Krill oil (KO) obtained from Euphausia superba is nutrient-rich and has a positive effect on human health. Here, we explored the efficacy of KO in inhibiting tumor progression and tumor vascularization. KO (100-300 µg/mL) repressed the proliferation of bladder tumor cell lines MBT-2 and T24. Treatment of cells with KO raised cell-cycle arrest at G0/G1-phase via modulation of positive regulators and negative regulators in bladder cancer cells. KO treatment regulated phosphorylation of proteins involved in PI3K/AKT and MAPK signaling pathways, including ERK, JNK, and p38 MAPK. Additionally, KO hampered the invasion and migration of both cell lines via reduction of MMP-9 expression levels by disrupting transcriptional binding of Sp-1, AP-1, and NF-κB motifs. Moreover, in animal studies, KO (150-300 mg/kg) significantly decreased tumor growth in xenograft mice bearing T24 tumor cells. No significant toxic effects were observed in acute toxicity tests, including biological analysis and H&E staining. The reduced level of CD31 expression in KO-treated tumor tissues prompted us to investigate the effect of KO on tumor angiogenesis. KO (5-40 µg/mL) treatment impeded VEGF-induced capillary tube formation and proliferation by inhibiting VEGFR2-modulated eNOS/AKT/ERK1/2 signaling axis in HUVECs. Treatment of HUVECs with KO inhibited VEGF-stimulated migration and invasion by reducing MMP-2 expression level. VEGF-driven sprouting capacity of neo-microvessels was suppressed in the presence of KO (20-40 µg/mL), as determined via an ex vivo aortic ring assay. Our results indicated that KO can regulate both tumor growth and tumor-associated angiogenesis via a novel mechanism. Thus, KO may be a promising antitumor candidate, potentially useful to prevent or treat bladder cancer.

Methods of the 2020 (Wave 1) International Tobacco Control (ITC) Korea Survey.

This article presents methods used in the 2020 International TC Korea Wave 1 (KRA1) Survey. To date, three cohorts of Korean respondents have participated in the larger ITC Korea Project (cohort 1: 2005-2014, cohort 2: 2016, and cohort 3: 2020-present). The overall objectives of the ITC KRA1 Survey were to examine the use of cigarettes, heated tobacco products (HTPs), e-cigarettes (ECs); whether HTPs might help smokers quit; and the effectiveness of tobacco control policies, such as large graphic warnings, high cigarette taxes, and smoking bans in public places. The KRA1 Survey measures were identical or functionally similar to those of the ITC Japan Survey and, to a lesser extent, those of other ITC countries. Key measures assessed sociodemographic characteristics of respondents; the use of combustible cigarettes, e-cigarettes, and heated tobacco products; and measures assessing policies of the WHO Framework Convention on Tobacco Control, including price and tax (Article 6), smoke-free laws (Article 8), health warnings (Article 11), education, communication and public awareness (Article 12), advertising, promotion, and sponsorship restrictions (Article 13), and support for cessation (Article 14). Adult tobacco and/or nicotine users aged ≥19 years in South Korea were recruited by a commercial survey firm from its online panel. Overall, 4794 respondents completed the KRA1 Survey. The cooperation rate was 97.4% and the response rate was 15.2%. The cohort design permits assessment of transitions in products used among users in South Korea and evaluations of the impact of policies on tobacco and/or nicotine products used and transitions in use.

Effects of Chitosan and Duck Fat-Based Emulsion Coatings on the Quality Characteristics of Chicken Meat during Storage.

Chicken meat is a popular food commodity that is widely consumed worldwide. However, the shelf-life or quality maintenance of chicken meat is a major concern for industries because of spoilage by microbial growth. The aim of this study was to evaluate the effects of chitosan and duck fat-based emulsion coatings on the quality characteristics and microbial stability of chicken meat during refrigerated storage. The coated chicken meat samples were as follows: control (non-coated), DFC0 (coated with duck fat), DFC0.5 (coated with duck fat and 0.5% chitosan), DFC1 (coated with duck fat and 1% chitosan), DFC2 (coated with duck fat and 2% chitosan), and SOC2 (coated with soybean oil and 2% chitosan). The results showed that the apparent viscosity and coating rate were higher in DFC2 than in other groups. Physicochemical parameters (pH, color, and Warner-Bratzler shear force) were better in DFC2 than those in other groups during 15 days of storage. Moreover, DFC2 delayed lipid oxidation, protein deterioration, and growth of microorganisms during storage. These data suggest that chitosan-supplemented duck fat-based emulsion coating could be used to maintain the quality of raw chicken meat during refrigerated storage.

Spatiotemporal Evaluation of Water Quality and Hazardous Substances in Small Coastal Streams According to Watershed Characteristics.

In this study, spatial and temporal changes of eight water quality indicators and 30 types of hazardous substances including volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), pesticides, and inorganic matters for the small coastal streams along the West Coast of South Korea were investigated. In coastal streams with clear seasonal changes in water quality, larger watershed areas led to greater contamination by particulate matter (i.e., suspended solids, r = 0.89), and smaller watershed areas led to greater contamination by organic matter (i.e., BOD, r = -0.78). The concentration of VOCs and pesticides was higher in agricultural areas, and those of SVOCs and metals were often higher in urban areas. According to the principal component analysis (PCA), during the wet season, the fluctuation in the water quality of coastal streams was higher in urban areas than in agricultural areas. Furthermore, coastal streams in residential areas exhibited higher levels of SVOCs, and those in industrial areas exhibited higher levels of metallic substances. Based on these results, the spatial and temporal trends of water quality and hazardous substances were obtained according to watershed characteristics, thereby clarifying the pollution characteristics of small-scale coastal streams and the major influencing factors.

Toxicity Assessment of a Single Dose of Poly(ethylene glycol) Diglycidyl Ether (PEGDE) Administered Subcutaneously in Mice.

Poly(ethylene glycol) diglycidyl ether (PEGDE) is widely used to cross-link polymers, particularly in the pharmaceutical and biomaterial sectors. However, the subcutaneous toxicity of PEGDE has not yet been assessed. PEGDE samples (500-40,000 µg/mouse) were subcutaneously injected into the paraspinal dorsum of BALB/c male mice. Cage-side observations were carried out with measurement of organ weight, body weight variation, and feed intake, as well as histopathological characterization on day 28 post-exposure. Mice that received 40,000 µg of PEGDE showed severe toxic response and had to be euthanized. Subcutaneous injection of PEGDE did not alter feed intake and organ weight; however, the body weight variation of mice injected with 20,000 µg of PEGDE was significantly lower than that of the other groups. Exposure to 10,000 and 20,000 µg of PEGDE induced epidermal ulcer formation and hair loss. The histology of skin tissue in mice administered with 20,000 µg of PEGDE showed re-epithelialized or unhealed wounds. However, the liver, spleen, and kidneys were histologically normal. Collectively, PEGDE, particularly above 10,000 µg/mouse, caused subcutaneous toxicity with ulceration, but no toxicity in the other organs. These results may indicate the optimal concentration of subcutaneously injected PEGDE.

Pseudoalteromone A, a Ubiquinone Derivative from Marine Pseudoalteromonas spp., Suppresses Melanogenesis.

An ubiquinone derivative, pseudoalteromone A (1), has been isolated from two marine-derived Pseudoalteromonas spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 µg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells.

Tebuconazole (TEB), a triazole fungicide, is frequently applied to agriculture for the increase of food production. Although TEB causes liver toxicity, its effects on cellular lipid accumulation are rarely investigated. Therefore, this study aimed to study the effects of TEB on lipid metabolism and accumulation in HepG2 cells. HepG2 cells were exposed to 0-320 µM TEB for 1-24 h. TEB (20-80 µM, 24 h)-treated cells showed lipid accumulation. Further, TEB (20-80 µM, 1-12 h) increased the nuclear translocation of peroxisome proliferator-activated receptors and the expression of lipid uptake and oxidation-related markers such as cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5, and carnitine palmitoyltransferase 1. Oxidative stress levels in TEB-treated cells (20-80 µM, 24 h) were higher, compared to those in the control. TEB (20-80 µM, 24 h) also induced the loss of mitochondrial membrane potential and lower levels of microsomal triglyceride transfer protein in the cells. Thus, TEB can induce lipid accumulation by altering the expression of lipid-metabolizing molecules and can therefore impair lipid metabolism. Our data suggest that human exposure to TEB may be a risk factor for non-alcoholic fatty liver disease.

Traceless Solid-Phase Synthesis of 7-Aminothiazolo[4,5-d]pyrimidine-Based Library via Dimroth Rearrangement.

Thiazolo[4,5-d]pyrimidine is one of the purine isosteres that possesses a variety of pharmaceutical activities and is an attractive scaffold for drug discovery. In this work, a novel protocol for the synthesis of 7-aminothiazolo[4,5,-d]pyrimidine scaffold libraries on solid support has been developed using a traceless linker. Dimroth rearrangement afforded the desired intermediate with a fused heterocyclic thiazolo[4,5,-d]pyrimidine core skeleton. To diversify the synthesized library, three types of building blocks were introduced to the resin-bound thiazolo[4,5,-d]pyrimidine through N-acylation, N-alkylation, and nucleophilic substitution with amines during cleavage from the resin. The synthesized compounds were produced in seven steps with overall yields of 11-48%. Additionally, physicochemical properties, as well as drug-likeness of the library, were calculated.

Differences in Clinical Characteristics and Chest Images between Coronavirus Disease 2019 and Influenza-Associated Pneumonia.

BACKGROUND: Concerns are arising about the simultaneous occurrence of the coronavirus disease 2019 (COVID-19) pandemic and the influenza epidemic, the so-called "twindemic". In this study, we compared clinical characteristics and chest images from patients with COVID-19 and influenza. METHODS: We conducted a case-control study of COVID-19 and age- and sex-matched influenza patients. Clinical characteristics and chest imaging findings between patients with COVID-19 and matched influenza patient controls were compared. RESULTS: A total of 47 patients were enrolled in each group. Anosmia (14.9%) and ageusia (21.3%) were only observed in COVID-19 patients. There were 31 (66%) and 23 (48.9%) patients with COVID-19 and influenza who had pulmonary lesions confirmed by chest computed tomography (CT), respectively. The interval between symptom onset and pneumonia was significantly longer in patients with COVID-19. Round opacities were more common in images from COVID-19 patients (41.9% vs. 8.7%, p = 0.007), whereas pure consolidation (0% vs. 34.9%, p < 0.001) and pleural effusion (0% vs. 17.4%, p = 0.028) were more common in images from influenza patients. Notably, the difference in the number of involved pulmonary lobes observed on CT and pulmonary fields observed on radiographic images was significantly higher in COVID-19-associated pneumonia than that in influenza-associated pneumonia (2.32 ± 1.14 vs. 1.48 ± 0.99, p = 0.010). CONCLUSIONS: Chest images and thorough review of clinical findings could provide value for proper differential diagnoses of COVID-19 patients, but they are not sufficiently sensitive for initial diagnoses. In addition, chest radiography could underestimate COVID-19 lung involvement because of the lesion characteristics of COVID-19-associated pneumonia.

Stress burden related to postreperfusion syndrome may aggravate hyperglycemia with insulin resistance during living donor liver transplantation: A propensity score-matching analysis.

BACKGROUND: We investigated the impact of postreperfusion syndrome (PRS) on hyperglycemia occurrence and connecting (C) peptide release, which acts as a surrogate marker for insulin resistance, during the intraoperative period after graft reperfusion in patients undergoing living donor liver transplantation (LDLT) using propensity score (PS)-matching analysis. PATIENTS AND METHODS: Medical records from 324 adult patients who underwent elective LDLT were retrospectively reviewed, and their data were analyzed according to PRS occurrence (PRS vs. non-PRS groups) using the PS-matching method. Intraoperative levels of blood glucose and C-peptide were measured through the arterial or venous line at each surgical phase. Hyperglycemia was defined as a peak glucose level >200 mg/dL, and normal plasma concentrations of C-peptide in the fasting state were taken to range between 0.5 and 2.0 ng/mL. RESULTS: After PS matching, there were no significant differences in pre- and intra-operative recipient findings and donor-graft findings between groups. Although glucose and C-peptide levels continuously increased through the surgical phases in both groups, glucose and C-peptide levels during the neohepatic phase were significantly higher in the PRS group than in the non-PRS group, and larger changes in levels were observed between the preanhepatic and neohepatic phases. There were higher incidences of C-peptide levels >2.0 ng/mL and peak glucose levels >200 mg/dL in the neohepatic phase in patients with PRS than in those without. PRS adjusted for PS with or without exogenous insulin infusion was significantly associated with hyperglycemia occurrence during the neohepatic phase. CONCLUSIONS: Elucidating the association between PRS and hyperglycemia occurrence will help with establishing a standard protocol for intraoperative glycemic control in patients undergoing LDLT.