Extrahepatic Malignancies and Antiviral Drugs for Chronic Hepatitis B: A Nationwide Cohort Study.

Background/Aims: Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Methods: Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. Results: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.1, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30). Conclusions: TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study.

BACKGROUND AND AIMS: No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. APPROACH AND RESULTS: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. CONCLUSIONS: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.

Effect of Crude Polysaccharides from Ecklonia cava Hydrolysate on Cell Proliferation and Differentiation of Hanwoo Muscle Stem Cells for Cultured Meat Production.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study.

BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.

The effects of different extraction methods on essential oils from orange and tangor: From the peel to the essential oil.

Citrus fruits are largely consumed due to their unique and pleasant aromas. Citrus hybrids have been developed to enhance their flavors and bioactivities. Citrus aroma depends on the composition of the volatile compounds in citrus essential oils (CEOs), which are mostly located in the peels. During the extraction of CEOs, a specific series of chemical reactions occurred depending on the extraction methods (CP, cold pressing; HD, hydrodistillation), leading to variations in the composition of volatile compounds. In this study, the orange and the tangor which is a hybrid between C. reticulata × C. sinensis were investigated to compare the changes in volatile compounds based on the extraction methods. Results showed that the CP-specific volatile compounds were sesquiterpenes, oxygenated monoterpenes, and fatty acid derivatives, while the HD-specific volatile compounds were terpinyl cation derivatives, limonene, and 4-vinylguaiacol. On the other hand, the contents of some volatile compounds ((E)-ocimene, α-terpinene, and α-terpinolene) were affected by the Citrus species rather than by the extraction methods. In particular, during HD, terpinene-4-ol and 4-vinylguiacol, known as off-flavor compounds in citrus juice, were formed more abundantly in the orange than in the tangor. In conclusion, these results provide comprehensive data on essential oils, especially those derived from oranges and tangors, for selecting the appropriate extraction method for obtaining a higher yield and quality of citrus flavor.

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND/AIM: Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT). METHODS: We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1. RESULTS: A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74). CONCLUSION: The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

Extrahepatic malignancies in metabolic dysfunction-associated fatty liver disease: A nationwide cohort study.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes. METHODS: This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality. RESULTS: In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001). CONCLUSION: The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.

Effects of Natural Extract Mixtures on the Quality Characteristics of Sausages during Refrigerated Storage.

Owing to the residual toxicity and adverse health effects of chemical preservatives, there is an increasing demand for using natural preservatives in food. Although many natural extracts have been evaluated, research on their antibacterial effects remains insufficient. Therefore, this study aimed to explore the possibility of developing Psidium guajava, Ecklonia cava, and Paeonia japonica (Makino) Miyabe & Takeda extracts as natural food preservatives. Further, the effect of mixing these extracts on microbial growth and quality was evaluated during the refrigeration of sausages. Optimal mixing ratios were determined based on the minimum inhibitory and bactericidal concentrations of each mixed extract against the Listeria monocytogenes, Salmonella spp. and Escherichia coli. D-optimal mixing design optimization tool was further used to obtain an optimum mixing ratio of Formulation 1 (F1). The antibacterial activity of F1 increased with increasing concentration, with similar activities at 0.5% and 1%. The sausages with synthetic or natural preservatives showed significantly lower lipid oxidation than those of the control and grapefruit extract-treated sausages after 4 wk of refrigeration. Total plate counts were observed only in the control and treatment groups stored for 3 wk, and no significant effect of ascorbic acid was observed. Compared to the other samples, sausages with added natural extracts showed the highest overall acceptability scores initially and after 4 wk. Therefore, similar amounts of grapefruit seed and natural extracts had the same effect on microbiological analysis and lipid rancidity during sausage storage. Hence, this mixture can serve as a potential natural preservative in meat products.

New Horizons: Translational Aspects of Osteomorphs.

Osteomorphs are a newly described osteoclast lineage cell in mice, which are suggested to play a significant role in the maintenance of bone resorption. Preclinical investigations revealed that osteomorphs are generated through the fission of multinucleated bone-resorbing osteoclasts and can also re-fuse with existing osteoclasts. Modifications to RANKL signaling have been shown to alter cycles of fission and re-fusion of osteomorphs in mice. These novel findings were also shown to contribute to the rebound phenomenon after cessation of anti-RANKL therapy in mice. Moreover, the absence of osteomorph-specific genes in mice exhibits bone structural and quality phenotypes. Given these insights, it could be speculated that osteomorphs play a significant role in bone homeostasis, bone metabolic diseases, and response to therapeutics. In this review, we discuss these potential translational roles for osteomorphs. Importantly, we highlight the need for future preclinical and clinical studies to verify the presence of osteomorphs in humans and explore further the translational implications of this discovery.

Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of foot-and-mouth disease.

The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease.

COVID-19 Vaccination Alters NK Cell Dynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log10 IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A+ NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A+ NK cells.

Integrated-Omics Study on the Transcriptomic and Metabolic Changes of Bacillus licheniformis, a Main Microorganism of Fermented Soybeans, According to Alkaline pH and Osmotic Stress.

Bacillus licheniformis has been widely utilized in the food industry as well as various agricultural industries. In particular, it is a main microorganism of fermented soybeans. In this study, the changes of the metabolome and transcriptome of B. licheniformis KACC15844, which had been isolated from fermented soybeans, were investigated depending on alkaline pH (BP) and a high salt concentration (BS) using an integrated-omics technology, focusing on leucine metabolism. Overall, carbohydrate (glycolysis, sugar transport, and overflow) and amino acid (proline, glycine betaine, and serine) metabolisms were strongly associated with BS, while fatty acid metabolism, malate utilization, and branched-chain amino acid-derived volatiles were closely related to BP, in both gene and metabolic expressions. In particular, in leucine metabolism, the formation of 3-methylbutanoic acid, which has strong cheesy odor notes, was markedly increased in BP compared to the other samples. This study provided information on how specific culture conditions can affect gene expressions and metabolite formations in B. licheniformis using an integrated-omics approach.

Robot versus human barista: Comparison of volatile compounds and consumers' acceptance, sensory profile, and emotional response of brewed coffee.

The increasing trend of integrating robots into the food industry has sparked debates regarding their potential influence on consumer attitudes toward food technology. This study investigated volatile compound profiles via gas chromatography-mass spectrometry (GC-MS), consumer acceptability, sensory profiling, and emotional responses of consumers toward coffee samples brewed by robot and human baristas. Moreover, the effect of the robot experience on food technology neophobia (FTN) was investigated. The principal component analysis of the volatile compound profiles revealed that the samples by the robot barista exhibited a higher degree of similarity compared to those prepared by the human barista. The range of relative standard deviations of volatile compounds from the robot barista brewed coffee was 1.4-83.1% and the variation was smaller than that of the human barista, which was 5.0-118.3%. Participants had a significant decrease in FTN scores after evaluating the robot-brewed coffee (p < 0.05), but there was no significant difference in FTN scores before and after evaluating the coffee brewed by the human barista (p > 0.05). Sensory evaluation studies revealed no significant differences in acceptability ratings and purchase intentions between the two groups (p > 0.05). However, emotional responses to the coffee samples significantly varied, with the robot-brewed coffee inducing more dynamic and positive emotions and the human-brewed coffee inducing more static and positive emotions (p < 0.05). Overall, this study provides valuable insights into consumer attitudes toward food robot service to humans and indicates that consumer's experience with food robots may significantly reduce FTN (p < 0.001).

Cross-Lagged Panel Analysis between Physical Frailty, Cognitive Function, and Falls by Sex.

OBJECTIVES: This study investigated the reciprocal longitudinal relationships between physical frailty (PF), cognitive function (CF), and falls among community-dwelling older adults, according to sex. The study proposed hypotheses that present PF and CF will affect the occurrence of falls 2 years later. DESIGN: Secondary data analysis using the first (T1, 2016-2017) and second (T2, 2018-2019) waves of the Korean Frailty and Aging Cohort Study (KFACS). SETTING AND PARTICIPANTS: A total of 2318 community-dwelling older adults aged 70-84 years in South Korea; mean (SD) age: 75.72 (3.83) years; 47.7% men. METHODS: PF and CF were measured with the modified version of the Fried Frailty Phenotype and the Korean version of the Mini-Mental State Examination, respectively. The number of falls were assessed. Multigroup cross-lagged panel analysis was used. RESULTS: The results showed that relationships between PF, CF, and falls were maintained over time through an autoregressive effect. PF at T1 had a statistically significant longitudinal relationship with fall experience at T2 [standardized regression coefficient (ß) = 0.087, 95% CI 0.045-0.129; P < .001], and fall experience at T1 had a significant longitudinal relationship with PF at T2 (ß = 0.041, 95% CI 0.006-0.076; P = .020). There was no statistically significant relationship between CF and fall experience. PF and CF had statistically significant reciprocal longitudinal relationships (all P < .001). Based on sex, there was a statistically significant longitudinal relationship between fall experience at T1 and PF at T2 for men only (ß = 0.063, 95% CI 0.012-0.114; P = .015). CONCLUSIONS AND IMPLICATIONS: Findings highlight that health care providers should plan fall prevention programs through early intervention for PF improvement along with improvement and maintenance of CF. Specifically, even if older men are currently healthy and have a low risk of falls, it is important to prevent future fatal PF through prior interventions, such as risk activities attention and concerns about falls.

[Psychometric Properties of the Korean Version of Self-Efficacy for HIV Disease Management Skills].

PURPOSE: This study evaluated the validity and reliability of Shively and colleagues' self-efficacy for HIV disease management skills (HIV-SE) among Korean participants. METHODS: The original HIV-SE questionnaire, comprising 34 items, was translated into Korean using a translation and back-translation process. To enhance clarity and eliminate redundancy, the author and expert committee engaged in multiple discussions and integrated two items with similar meanings into a single item. Further, four HIV nurse experts tested content validity. Survey data were collected from 227 individuals diagnosed with HIV from five Korean hospitals. Construct validity was verified through confirmatory factor analysis. Criterion validity was evaluated using Pearson's correlation coefficients with the new general self-efficacy scale. Internal consistency reliability and test-retest were examined for reliability. RESULTS: The Korean version of HIV-SE (K-HIV-SE) comprises 33 items across six domains: "managing depression/mood," "managing medications," "managing symptoms," "communicating with a healthcare provider," "getting support/help," and "managing fatigue." The fitness of the modified model was acceptable (minimum value of the discrepancy function/degree of freedom = 2.49, root mean square error of approximation = .08, goodness-of-fit index = .76, adjusted goodness-of-fit index = .71, Tucker-Lewis index = .84, and comparative fit index = .86). The internal consistency reliability (Cronbach's α = .91) and test-retest reliability (intraclass correlation coefficient = .73) were good. The criterion validity of the K-HIV-SE was .59 (p < .001). CONCLUSION: This study suggests that the K-HIV-SE is useful for efficiently assessing self-efficacy for HIV disease management.

Black Wheat Extracts (Arriheuk) Regulate Adipogenesis and Lipolysis via Adenosine Monophosphate (AMP) Activated Protein Kinase (AMPK)/Sirtuin 1 (SIRT1) Signaling Pathways.

Polyphenols and other compounds with antioxidant properties are found in plants and are one of the main antioxidants proven to reduce body weight and the risk of insulin resistance. Still, the mechanism behind the protective effects against obesity remains unclear. Thus, the study aims to assess the impact of flavonoid-rich arriheuk extract, a purple wheat extract, on mitochondrial function using 3T3-L1 adipocytes and investigate the molecular mechanism behind its protective effects against adipogenesis and lipolysis. The study findings strongly indicate that arriheuk significantly suppressed triglyceride levels and inhibited the expression of transcription factors like C/EBPα and PPARγ in 3T3-L1 adipocytes. Furthermore, treatment with arriheuk suppressed the expression of SREBP1c and FAS proteins linked to lipogenesis. In addition, treatment with arriheuk extract decreased the mRNA levels of adipogenic transcription factors, increased glycerol release, and inhibited adipocyte differentiation. Interestingly, the arriheuk-mediated PGC-1α expression triggered mitochondrial biogenesis by promoting the AMPK phosphorylation and SIRT1 expression in adipocytes. Also, arriheuk suppressed adipogenesis and elicited browning through the AMPK- and SIRT1-associated pathways. Collectively, these findings strongly suggest that arriheuk extract regulates browning in 3T3-L1 white adipocytes by triggering the AMPK/SIRT1 pathway, indicating the prospective applications of arriheuk as a functional food to control obesity.

Accumulation of plasmacytoid dendritic cell is associated with a treatment response to DNA-damaging treatment and favorable prognosis in lung adenocarcinoma.

Introduction: Favorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status. Methods: Lung adenocarcinoma (LUAD) tissue (Tu) and adjacent normal-appearing lung tissue (NL) from current and never smokers were investigated by single-cell RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets. Results: The lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers' Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch's two-sample t-test). Conclusion: There is an increased pDC in the TME of smokers' lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.

Origin of Osteoclasts: Osteoclast Precursor Cells.

Osteoclasts are multinucleated bone-resorbing cells and a key player in bone remodeling for health and disease. Since the discovery of osteoclasts in 1873, the structure and function of osteoclasts and the molecular and cellular mechanisms of osteoclastogenesis have been extensively studied. Moreover, it has been well established that osteoclasts are differentiated in vitro from myeloid cells such as bone marrow macrophages or monocytes. The concept showing that osteoclasts are derived from a specific population (named osteoclast precursor cells [OCPs]) among myeloid cells has been long hypothesized. However, the specific precursor population of osteoclasts is not clearly defined yet. A growing body of work provides evidence of the developmental origin and lifespan of murine osteoclasts, particularly in vivo. Here, we review the emerging evidence that supports the existence of OCPs and discuss current insights into their identity.

Application of Schizosaccharomyces japonicus in makgeolli fermentation and its brewing characteristics.

Recently, unconventional yeasts have become popular as fermentation starters in the brewing industry due to the growing consumer demand for aromatic diversity. Specifically, Schizosaccharomyces japonicus has been explored as a potential starter culture for beer and wine production because of its distinct brewing characteristics; however, its application in makgeolli fermentation has not been tested. Therefore, in the present study, two Sz. japonicus strains (SZJ-1 and SZJ-2) were isolated from natural sources, and their brewing characteristics for makgeolli fermentation were compared with those of commercial S. cerevisiae strain. Although the tested isolates showed a lower fermentation and carbon source consumption rate than control-, their overall alcohol fermentation characteristics were suitable for makgeolli production. Regarding flavor composition, Sz. japonicus-fermented makgeolli possessed more ester compounds (e.g., 2-phenylethyl acetate, ethyl acetate, and ethyl decanoate) than S. cerevisiae-fermented makgeolli. Therefore, Sz. japonicus can be used as an alternative culture starter in makgeolli fermentation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01265-6.

The association between depression and non-compliance with COVID-19 preventive behaviors in South Korean older adults stratified by sex.

OBJECTIVES: This study evaluated the association between depression and non-compliance with COVID-19 preventive behaviors among community-dwelling South Korean older adults. METHODS: We utilized the 2020 Korean Community Health Survey-a community-based nationwide survey. A score of 10 points or higher on the Patient Health Questionnaire-9 was defined as depression. Non-compliance with COVID-19 preventive behaviors was assessed on the following three behaviors: washing hands, wearing masks, and watching distance. We also included socio-demographic characteristics, health behaviors, and COVID-19-related characteristics as covariates. Multiple logistic regression analyses were performed, and all statistical analyses were stratified by sex. RESULTS: The 70,693 participants included 29,736 men and 40,957 women. Notably, 2.3% of men and 4.2% of women had depression. Non-compliance with washing hands was significantly higher in men than women (1.3% vs. 0.9%), whereas no significant differences were observed in wearing masks and watching distance. The adjusted logistic regression analysis showed that depression was positively associated with non-compliance with washing hands and watching distance in both sexes. The association between depression and non-compliance with wearing masks was significant only in women. CONCLUSIONS: There was an association between depression and non-compliance with COVID-19 preventive behaviors in South Korean older adults. This signifies that health providers need to reduce depression to improve compliance with preventive behaviors in older adults.