Kinetics-based inference of environment-dependent microbial interactions and their dynamic variation.

Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. The effectiveness of our method was experimentally demonstrated using a synthetic consortium of two Escherichia coli mutants that are metabolically dependent (due to an inability to synthesize essential amino acids) but competitively grow on a shared substrate. The analysis of the E. coli binary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions, such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer the complex dynamics of microbial communities. Moreover, the prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among macroorganisms, such as plants and animals, as well as microorganisms.

Antibiotic resistance in livestock, environment and humans: One Health perspective.

Antibiotic resistance (AR) is a complex, multifaceted global health issue that poses a serious threat to livestock, humans, and the surrounding environment. It entails several elements and numerous potential transmission routes and vehicles that contribute to its development and spread, making it a challenging issue to address. AR is regarded as an One Health issue, as it has been found that livestock, human, and environmental components, all three domains are interconnected, opening up channels for transmission of antibiotic resistant bacteria (ARB). AR has turned out to be a critical problem mainly because of the overuse and misuse of antibiotics, with the anticipation of 10 million annual AR-associated deaths by 2050. The fact that infectious diseases induced by ARB are no longer treatable with antibiotics foreshadows an uncertain future in the context of health care. Hence, the One Health approach should be emphasized to reduce the impact of AR on livestock, humans, and the environment, ensuring the longevity of the efficacy of both current and prospective antibiotics.

Qualitative and Quantitative Metabolite Comparison of Korean Traditional Alcoholic Beverages: Takju, Yakju, and Traditional-Soju.

With increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.

Metabolomics Reveals the Effects of Nitrogen/Phosphorus/Potassium (NPK) Fertilizer Levels on Cucumber Fruit Raised in Different Nutrient Soils.

Fertilizers are widely used to improve the quality of fruits and vegetables. However, the overuse of fertilizers has become an issue because it causes environmental problems and negatively affects productivity and fruit quality. In this study, we examined the effects of nitrogen, phosphorus, and potassium (NPK) fertilizer levels on the metabolism of cucumber fruit in low- and high-nutrient soils using mass-spectrometry-based metabolomics approaches. Cucumber metabolite content was notably different depending on the initial soil nutrient status. Most amino acids and phenylpropanoids were abundant in the cucumbers raised in low-nutrient soil, whereas organic acids, some amino acids (aspartate, glutamate, and ornithine), and carbohydrates were comparatively higher in fruits from high-nutrient soil. The fertilizer supply resulted in an alteration in the metabolite profile, while no change in fruit yield was observed in either low- or high-nutrient soils. Fertilizer treatment perturbed the metabolite contents in cucumbers from low-nutrient soil. In contrast, treatment with higher concentrations of fertilizer in high-nutrient soil increased phenylpropanoid content in the cucumbers, while most metabolites decreased. In conclusion, fertilization levels should be carefully determined, considering culture conditions such as the original soil status, to increase product yield and fruit quality and avoid environmental problems.

Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis.

We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Combination of Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 attenuates fat accumulation and alters the metabolome and gut microbiota in mice with high-fat diet-induced obesity.

This study evaluated the effects of formulations with Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 on adiposity, the alteration of microbiota, and the metabolome in high-fat diet-fed mice. The strains were selected based on their fat and glucose absorption inhibitory activities and potential metabolic interactions. The optimal ratio of the two strains in the probiotic formulation was determined based on their adipocyte differentiation inhibitory activities. Treatment of formulations with BEPC22 and BELP53 for 10 weeks decreased body weight gain at 6 weeks; it also decreased the food efficiency ratio, white adipose tissue volume, and adipocyte size. Moreover, it decreased the expression of the lipogenic gene Ppar-γ in the liver, while significantly increasing the expression of the fat oxidation gene Ppar-α in the white adipose tissue. Notably, treatment with a combination of the two strains significantly reduced the plasma levels of the obesity hormone leptin and altered the microbiota and metabolome. The omics data also indicated the alteration of anti-obesity microbes and metabolites such as Akkermansia and indolelactic acid, respectively. These findings suggest that treatment with a combination of BEPC22 and BELP53 exerts synergistic beneficial effects against obesity.

Who Hurt You at Work? Results From a Nationwide Survey of Association Between Absenteeism and Workplace Violence, Stratified by Perpetrator.

OBJECTIVE: This study aimed to determine the association between workplace violence and sickness absenteeism. METHODS: We analyzed the data from the fifth and sixth waves of the Korean Working Conditions Surveys. Individuals younger than 18 years and self-employed or unpaid family workers were excluded. Descriptive statistics, χ 2 tests, and multiple logistic regression analysis were conducted. RESULTS: After adjusting for sociodemographic, occupational, and job-related characteristics, we found that the workers who had experienced workplace violence had higher rates of sickness absenteeism, especially when the perpetrator of violence was a coworker. CONCLUSIONS: Daily contact with the perpetrator at the workplace can cause distress and recollection of painful memories; thus, the aftermath of being harassed inside the workplace can be even more devastating than the event itself. A sensitive approach to recognizing the perpetrators of violence is needed.

Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer's Disease.

Targeted protein degradation (TPD) provides unique advantages over gene knockdown in that it can induce selective degradation of disease-associated proteins attributed to pathological mutations or aberrant post-translational modifications (PTMs). Herein, we report a protein degrader, PRZ-18002, that selectively binds to an active form of p38 MAPK. PRZ-18002 induces degradation of phosphorylated p38 MAPK (p-p38) and a phosphomimetic mutant of p38 MAPK in a proteasome-dependent manner. Given that the activation of p38 MAPK plays pivotal roles in the pathophysiology of Alzheimer's disease (AD), selective degradation of p-p38 may provide an attractive therapeutic option for the treatment of AD. In the 5xFAD transgenic mice model of AD, intranasal treatment of PRZ-18002 reduces p-p38 levels and alleviates microglia activation and amyloid beta (Aß) deposition, leading to subsequent improvement of spatial learning and memory. Collectively, our findings suggest that PRZ-18002 ameliorates AD pathophysiology via selective degradation of p-p38, highlighting a novel therapeutic TPD modality that targets a specific PTM to induce selective degradation of neurodegenerative disease-associated protein.

Association between receiving work communications outside of work hours via telecommunication devices and work-related headaches and eyestrain: a cross-sectional analysis of the 6th Korean Working Conditions Survey.

Background: The rise in telecommuting or non-face-to-face work owing to the coronavirus disease 2019 pandemic has fueled conversations regarding the "right to disconnect." Although evidence suggests that receiving work-related communications through telecommunication devices outside of work hours may lead to various symptoms and illnesses, limited research has been undertaken on these symptoms. This study therefore aims to investigate the correlation between receiving work communications through telecommunication devices after work hours and the occurrence of work-related headaches and eyestrain in full-time, non-shift white-collar workers. Methods: This study used data from the 6th Korean Working Conditions Survey. The frequency of using telecommunication devices for work purposes outside of working hours was divided into five categories: "Every day," "Several times a week," "Several times a month," "Rarely," and "Never." Work-related headaches and eyestrain were categorized based on a "yes" or "no" response to the survey questions. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using SPSS 27.0. Results: After adjusting for sex, age, income level, education, occupation, workplace size, work hours, and sleep disorders, the odds ratio (OR) of work-related headaches and eyestrain based on frequency of telecommunication device usage were as follows: "rarely" (OR: 1.292; 95% confidence interval [CI]: 1.111-1.503), "several times a month" (OR: 1.551; 95% CI: 1.249-1.926), "several times a week" (OR: 1.474; 95% CI: 1.217-1.784), and "every day" (OR: 1.548; 95% CI: 1.321-1.813). Conclusions: Employees who use telecommunication devices for work after regular hours are more susceptible to experiencing work-related headaches and eyestrain compared to those who do not. However, there is a dearth of research examining the physical and mental health impacts of using telecommunication devices for after-hours work. Furthermore, the existing preventative measures in Korea are insufficient. Consequently, it is imperative to develop effective measures and conduct additional research to address this issue.

Comprehensive Metabolite Profiling of Four Different Beans Fermented by Aspergillus oryzae.

Fermented bean products are used worldwide; most of the products are made using only a few kinds of beans. However, the metabolite changes and contents in the beans generally used during fermentation are unrevealed. Therefore, we selected four different beans (soybean, Glycine max, GM; wild soybean, Glycine soja, GS; common bean, Phaseolus vulgaris, PV; and hyacinth bean, Lablab purpureus, LP) that are the most widely consumed and fermented with Aspergillus oryzae. Then, metabolome and multivariate statistical analysis were performed to figure out metabolite changes during fermentation. In the four beans, carbohydrates were decreased, but amino acids and fatty acids were increased in the four beans as they fermented. The relative amounts of amino acids were relatively abundant in fermented PV and LP as compared to other beans. In contrast, isoflavone aglycones (e.g., daidzein, glycitein, and genistein) and DDMP-conjugated soyasaponins (e.g., soyasaponins ßa and γg) were increased in GM and GS during fermentation. Notably, these metabolite changes were more significant in GS than GM. In addition, the increase of antioxidant activity in fermented GS was significant compared to other beans. We expect our research provides a basis to extend choice for bean fermentation for consumers and food producers.

Epidemiologic outlook of therapy-related myeloid neoplasms and selection of high-risk patients: A Korean nationwide study.

BACKGROUND: Although a considerable proportion of patients with cancer receive chemotherapy (CT) or radiotherapy (RT), only a very few patients eventually develop therapy-related myeloid neoplasms (t-MNs). METHODS: To identify subsets of cancer patients who have substantially elevated risk of developing t-MNs. Incidences and risks of t-MNs after contemporary CT or RT in patients newly diagnosed major cancers during 2009-2013 were analyzed. By merging two Korean nationwide health care big data sets, patients were selected and observed on follow-up to until t-MN development or December 2019. RESULTS: Among 250,155 patients, 555 (0.22%) were diagnosed with t-MNs with a standard incidence ratio (SIR) of 3.40 (95% CI, 3.13-3.70). Patients had bone/joint cancers (SIR, 94.25; 95% CI, 50.71-137.80) and a remarkably high SIR for t-MN development. Patients receiving both CT and RT had the highest SIR (4.64; 95% CI, 4.08-5.20), followed by those receiving CT only (SIR, 3.30; 95% CI, 2.89-3.70). Contrarily, RT alone did not increase t-MN risk (SIR, 1.16; 95% CI, 0.76-1.56). More exposure to leukemogenic agents resulted in the higher t-MNs development. CONCLUSIONS: The increased risk of developing acute myeloid leukemia or myelodysplastic syndrome after CT and/or RT was confirmed and subsets with substantially elevated risk for developing t-MNs were found. Such patients would be suitable for a prospective cohort for investigating t-MN pathogenesis by time series analyses.

Relationship between workplace violence and work-related depression/anxiety, separating the types of perpetrators: a cross-sectional study using data from the fourth and fifth Korean Working Conditions Surveys (KWCS).

Background: Work is an inseparable element of a person's life, and violence in the workplace has various effects on individual workers and companies. While most studies have focused on specific industries, very few studies have investigated the influence of workplace violence by co-workers. Therefore, this study aimed to evaluate the association between workplace violence and work-related depression/anxiety in various occupations by differentiating the perpetrators of violence as co-workers and clients. Methods: This study was conducted based on data from the 4th and 5th Korean Working Conditions Surveys (KWCS). The experience of workplace violence was classified in terms of the perpetrator: workplace violence by co-workers and that by clients. Work-related depression and anxiety were assessed using questions about health problems related to depression and anxiety and whether the problems were related to work. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using the SPSS 26.0. Results: After adjusting for sociodemographic characteristics (age, education, income, subjective health status) and occupational characteristics (occupation, weekly working hours, type of employment, size of workplace, and shift work), male workers with experience of workplace violence by co-workers were found to be at a higher risk of work-related depression/anxiety (odds ratio [OR], 11.52; 95% confidence interval [CI], 8.65-15.36). The same was confirmed for female workers (OR, 10.89; 95% CI, 7.90-15.02). Conclusions: Employees who experienced workplace violence from co-workers were found to be more vulnerable to work-related depression/anxiety. Continuous contact between the victim and the perpetrator may occur, and the possibility of a secondary assault can frighten the victim. Appropriate prevention and intervention measures that focus on the perpetrators of violence are needed.

Comparing risk of depression between day and night/shift workers using the PHQ-9: a study utilizing the 2014, 2016, and 2018 Korea National Health and Nutrition Examination Survey data.

BACKGROUND: In today's work scenario, the number of shift workers, including those in night shifts, is increasing. Shift work can adversely affect workers' health in the long run, but studies on the relationship between shift work and depression have shown inconsistent results. This study aimed to determine whether the number of night/shift workers at risk of depression, as predicted by the Patient Health Questionnaire-9 (PHQ-9), is higher than that of day workers. METHODS: This study was conducted based on data from the 6th and 7th Korea National Health and Nutrition Examination Survey, 2014, 2016, and 2018. Work schedules were classified into 2 types: day work and night/shift work. This study used the PHQ-9, a self-reported depression screening test, to identify workers at risk of depression. Statistical analysis was performed using SPSS 26.0, and descriptive statistics, χ2 test, and logistic regression analysis were employed. RESULTS: After adjusting for age, educational level, working hours per week, and income, men engaging in night/shift work were at a higher risk of depression (odds ratio [OR]: 1.407, 95% confidence interval [CI]: 0.937-2.113). The same was confirmed for women (OR: 1.564, 95% CI: 1.176-2.081). CONCLUSIONS: Our results showed that the OR for those engaged in night/shift work with a PHQ-9 score of 10 or more increased. Considering the large volume of psychiatric history and symptoms in Korea, additional research is needed. Additionally, further discussion on ways to provide realistic help to night/shift workers is warranted.

Changes in the Prosthesis Types Used for Aortic Valve Replacement after the Introduction of Sutureless and Rapid Deployment Valves in Korea: A Nationwide Population-Based Cohort Study.

BACKGROUND: Sutureless and rapid deployment valves for aortic valve replacement (AVR) were introduced in Korea in December 2016. This study evaluated changing trends in the prosthetic valves used for AVR in Korea after the introduction of sutureless and rapid deployment valves. METHODS: From December 2016 to December 2018, 4,899 patients underwent AVR in Korea. After applying the exclusion criteria, 4,872 patients were analyzed to determine changes in the type of prosthetic valve used for AVR. The study period was divided into 5 groups corresponding to 5-month intervals. RESULTS: The total number of AVR cases was 194.88±28.78 per month during the study period. Mechanical valves were used in approximately 27% to 33% of cases, and the proportion of mechanical valve use showed a tendency to decrease, with marginal significance overall (p=0.078) and significant decreases in patients less than 60 years of age and in men (p=0.013 and p=0.023, respectively). The use of sutureless valves increased from 13.4% to 25.8% of cases (p<0.001), especially in elderly patients (>70 years) and those requiring concomitant surgery. In a comparison between sutureless and rapid deployment valves, the use of Perceval S valves (a type of sutureless valve), gradually increased (p<0.001). CONCLUSION: After the introduction of sutureless and rapid deployment valves in Korea, the rate of use of these new valves remarkably increased, especially in elderly patients and those requiring concomitant surgery. Further studies should investigate the clinical outcomes of these new prostheses.

Der p 38 Is a Bidirectional Regulator of Eosinophils and Neutrophils in Allergy.

The house dust mite is the most common cause of allergic diseases, and TLR4 acts as an overarching receptor for allergic responses. This study aimed to identify novel allergen binding to TLR4 in house dust mites and unveil its unique role in allergic responses. Der p 38 was purified and characterized by liquid chromatography tandem mass spectrometry-based peptide mapping. Biolayer interferometry and structure modeling unveiled TLR4-binding activity and the structure of recombinant Der p 38. The allergenicity of Der p 38 was confirmed by a skin prick test, and basophil activation and dot blot assays. The skin prick test identified 24 out of 45 allergic subjects (53.3%) as Der p 38+ subjects. Der p 38-augmented CD203c expression was noted in the basophils of Der p 38+ allergic subjects. In animal experiments with wild-type and TLR4 knockout BALB/c mice, Der p 38 administration induced the infiltration of neutrophils as well as eosinophils and exhibited clinical features similar to asthma via TLR4 activation. Persistent Der p 38 administration induced severe neutrophil inflammation. Der p 38 directly suppressed the apoptosis of allergic neutrophils and eosinophils, and enhanced cytokine production in human bronchial epithelial cells, inhibiting neutrophil apoptosis. The mechanisms involved TLR4, LYN, PI3K, AKT, ERK, and NF-κB. These findings may contribute to a deep understanding of Der p 38 as a bridge allergen between eosinophilic and neutrophilic inflammation in the pathogenic mechanisms of allergy.

Metabolomic-Based Comparison of Traditional and Industrial Doenjang Samples with Antioxidative Activities.

Numerous varieties of doenjang are manufactured by many food companies using different ingredients and fermentation processes, and thus, the qualities such as taste and flavor are very different. Therefore, in this study, we compared many products, specifically, 19 traditional doenjang (TD) and 17 industrial doenjang (ID). Subsequently, we performed non-targeted metabolite profiling, and multivariate statistical analysis to discover distinct metabolites in two types of doenjang. Amino acids, organic acids, isoflavone aglycones, non-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4- one) soyasaponins, hydroxyisoflavones, and biogenic amines were relatively abundant in TD. On the contrary, contents of dipeptides, lysophospholipids, isoflavone glucosides and DDMP-conjugated soyasaponin, precursors of the above-mentioned metabolites, were comparatively higher in ID. We also observed relatively higher antioxidant, protease, and ß-glucosidase activities in TD. Our results may provide valuable information on doenjang to consumers and manufacturers, which can be used while selecting and developing new products.

Three-Year Follow-Up of Laser In Situ Keratomileusis Treatments for Myopia: Multi-Center Cohort Study in Korean Population.

This multi-center cohort study included 3401 myopic laser in situ keratomileusis (LASIK) procedures conducted in 1756 myopia patients between 2002 and 2005. Pre- and postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and manifest refraction spherical equivalent (SE) were recorded. Factors predicting low postoperative efficacy (defined as a postoperative UCVA < 0.5) were identified using univariate and multivariate logistic regression analysis. Compared with 1 month postoperatively, logMAR UCVA at 3 months postoperatively was significantly decreased (p = 0.002) and that at 2 and 3 years was significantly increased (p < 0.001). LogMAR BCVA at 2 years postoperatively was significantly decreased compared with 1 month postoperatively (p = 0.008). Over the 3-year postoperative period, overall refractive predictability within ±1.00 D and ±0.50 D ranged from 69.0% to 86.2% and from 43.3% to 67.8%, respectively. This also decreased from 1 month to 6 months postoperatively (p < 0.005). Multivariate logistic regression analysis using generalized estimating equations, revealed that higher preoperative SE (odds ratio [OR], 2.58 and 7.23; p < 0.001) and lower preoperative BCVA (OR, 2.44; p = 0.003) were predictive of a low postoperative efficacy. In summary, myopic LASIK can be effective and safe with a high refractive predictability in a Korean population, but myopic regression occurs over time. Higher preoperative SE and lower preoperative BCVA are predictive of a low postoperative efficacy.

Comparing Metabolites and Functional Properties of Various Tomatoes Using Mass Spectrometry-Based Metabolomics Approach.

Tomato is one of the world's most consumed vegetables, and thus, various cultivars have been developed. Therefore, metabolic differences and nutrient contents of various tomatoes need to be discovered. To do so, we performed metabolite profiling along with evaluation of morphological and physicochemical properties of five representative tomato types. Common tomato cultivars, bigger and heavier than other tomatoes, contained higher levels of amino acids, organic acids, and lipids. On the contrary, cherry tomato cultivars contained a higher proportion of phenylpropanoids, lycopene, ß-carotene, and α-carotene than the other tomatoes. Also, the highest antioxidant activity and total phenolic and flavonoid contents were observed in cherry tomato cultivars. Furthermore, to understand metabolic distributions in various tomato cultivars, we constructed a metabolic pathway map. The higher metabolic flux distribution of most primary metabolite synthetic pathways was observed in common tomatoes, while cherry tomato cultivars showed a significantly elevated flux in secondary metabolite synthetic pathways. Accordingly, these results provide valuable information of different characteristics in various tomatoes, which can be considered while purchasing and improving tomato cultivars.

Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs.

A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.

Early and Two-year Outcomes after Sutureless and Conventional Aortic Valve Replacement: a Nationwide Population-based Study.

BACKGROUND: We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. METHODS: From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. RESULTS: Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR grouP = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). CONCLUSION: Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group.