P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

Background: COVID-19 booster uptake remained poor among healthcare workers (HCW) despite evidence of improved immunity against Delta and Omicron variants. While most studies used a questionnaire to assess hesitancy, this study aimed to identify factors affecting true booster hesitancy by examining actual vaccine uptake across time. Method: COVID-19 vaccination database records among HCW working at 7 Singaporean public primary care clinics between January to December 2021 were extracted, with gender, profession, place of practice, vaccination type and dates. Time to booster was calculated from the date of vaccination minus date of eligibility. Chi-square test was used to compare relationship between 1st dose and booster hesitancy, Kaplan-Meier method and Log-rank test were adopted to evaluate differences in cumulative booster uptake. Multivariate cox regression was used to investigate predictors for timely booster vaccination. Vaccination rate was charted across time and corroborated with media releases pertaining to legislative changes. Results: 877 of 891 (98.9%) primary care HCW were fully vaccinated, 73.8% of eligible HCW had taken the booster. HCW were less booster hesitant [median 16 (5-31.3) days] compared to the 1st dose [median 39 (13-119.3) days]. 1st dose hesitant HCW were more likely to be booster hesitant (OR=3.66, 95%CI 2.61-5.14). Adjusting for sex, workplace and time to 1st dose, ancillary (HR=1.53, 95%CI 1.03-2.28), medical (HR=1.8, 95%CI 1.18-2.74) and nursing (HR=1.8, 95%CI 1.18-2.37) received boosters earlier compared with administrative staff. No temporal relationship was observed between booster uptake, legislative changes and COVID-19 infection numbers. Conclusion: Vaccine hesitancy among HCW had improved from booster to 1st dose, with timely booster vaccination among medical and nursing staff. Tailored education, risk messaging and strategic legislation might help to reduce delayed booster vaccination.

We investigated the potential genetic variants using whole exome sequencing (WES) and evalu-ated the disease course using T cell receptor (TCR) repertoire analysis in rheumatoid arthritis (RA). Fourteen patients with RA and five healthy controls (HCs) were enrolled. For patients with RA, only naïve patients were recruited before treatment, and data were collected at baseline and 6 and 12 months after the initiation of disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using Shannon-Weiner diversity. Some variants were detected by WES, but their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in patients with RA was lower than that in HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively cor-related with laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified and the clinical significance of TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Spices rich in polyphenols are metabolized to a convergent group of phenolic acids. We conducted a dose-exposure nutrikinetic study to investigate associations between mixed spices intake and plasma concentrations of selected, unconjugated phenolic acids. In a randomized crossover study, 20 Chinese males consumed a curry meal containing 0 g, 6 g, and 12 g of mixed spices. Postprandial blood was drawn up to 7 h at regular intervals and plasma phenolic acids were quantified via LC-MS/MS. Cinnamic acid (CNA, p < 0.0001) and phenylacetic acid (PAA, p < 0.0005) concentrations were significantly increased with mixed spices consumption, although none of the other measured phenolic acids differ significantly between treatments. CNA displayed a high dose-exposure association (R² > 0.8, p < 0.0001). The adjusted mean AUC_{0-7 h} for CNA during the 3 increasing doses were 8.4 ± 3.4, 376.1 ± 104.7 and 875.7 ± 291.9 nM·h respectively. Plasma CNA concentration may be used as a biomarker of spice intake.

This study entailed the design and analysis of a 400 m-class underwater glider operated by a bladder-type buoyancy engine. The underwater glider was designed for high-speed movement with a maximum velocity of 2 knots. The shape of the hull was designed to reduce water resistance using the Myring hull profile equation. The reliability was verified by performing simulations using resistance coefficients. The relationship between the control value of the ballast discharged from the buoyancy engine and the glider's speed according to the path angle was analyzed. Further, the relationship between the optimal glide angle and the design control value of the ballast was derived, and the optimal glider speed was estimated accordingly. Based on the analysis results, a bladder-type buoyancy engine was developed, and the maximum speed of the tested underwater glider was measured via sea trials.

It is required to manage sustainable Short-Rotation Coppices (SRCs) as an important role on carbon sink and bioenergy output, because most of SRCs were established in reclaimed land in South Korea. However, during the last three years, growth pattern of the SRCs was remarkably changed with soil condition. This study aimed to identify the sustainability of SRCs on carbon storage, biomass and fuel pellet production, monitoring the neighboring vegetation of SRCs by land-use exchange, physiological change of poplar on seasonal trend, and to evaluate whether poplar is suitable for making wood pellets. The calculated biomass yield per area of poplar grown was 103.07 Mg per total area (55.6 ha), and volumes of carbon dioxide absorption was estimated to be 330 Mg CO2. Wood pellet quality based on the criteria scored third grade, indicating that poplar is suitable for manufacturing fuel pellets. Moreover, monitoring of the flora distribution in SRCs revealed changes in species composition. As halophyte was increased during drought, soil organic matter, net growth and total chlorophyll of poplar were significantly decreased. These findings indicated that photosynthesis and growth pattern of SRCs may be negatively affected by microclimate and will provide valuable information for effective management of SRCs.

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in the elderly, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between Low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyzes were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived after a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pain. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise Lower ASM was moderately associated with LBP and knee pain, while higher ASM correlated with engagement in regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pain. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

To determine the mode of action of the effects of phytoalexins in soybeans, we analyzed enzyme inhibition kinetics using Michaelis–Menten plots and the Lineweaver–Burk plots. The results showed that glyceollin showed competitive inhibition, genistein showed noncompetitive, daidzein was uncompetitive, and luteolin showed a mixed mode of action. The Ki values were determined using a Dixon plot as: glyceollin, 18.99; genistein, 15.42; luteolin, 16.81; and daidzein, 9.99 μM, respectively. Furthermore, potential synergistic effects between glyceollin and the three designated polyphenols were investigated. A combination of glyceollin and luteolin (the ratio of 3:7 of glyceollin and luteolin) had synergistic effects on α-glucosidase inhibition according to combination index (CI)-isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit α-glucosidase activity via a synergistic mode of action.

The outbreak of novel coronavirus (COVID-19) infections in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking to repurpose HIV protease inhibitors and nucleoside analogues for COVID-19, with evaluations based on docking scores calculated by AutoDock Vina and RosettaCommons. Our results suggest that Indinavir and Remdesivir possess the best docking scores, and comparison of the docking sites of the two drugs reveal a near perfect dock in the overlapping region of the protein pockets. After further investigation of the functional regions inferred from the proteins of SARS coronavirus, we discovered that Indinavir does not dock on any active sites of the protease, which may give rise to concern in regards to the efficacy of Indinavir. On the other hand, the docking site of Remdesivir is not compatible with any known functional regions, including template binding motifs, polymerization motifs and nucleoside triphosphate (NTP) binding motifs. However, when we tested the active form (CHEMBL2016761) of Remdesivir, the docking site revealed a perfect dock in the overlapping region of the NTP binding motif. This result suggests that Remdesivir could be a potential therapeutic agent. Clinical trials still must be done in order to confirm the curative effect of these drugs.