Impact of Taekwondo training on cognitive and physical function in elderly individuals: A comprehensive review of randomized controlled trials.

BACKGROUND: Researchers have investigated the physical and psychosocial advantages of Taekwondo for older adults. However, prior studies of Taekwondo's impact on physical function and psychological well-being in this demographic have produced inconsistent findings. Thus, this systematic review aimed to assess how Taekwondo practice affects the physical function and psychological well-being of older adults. METHODS: We systematically searched PubMed, EMBASE, CINAHL, SPORTDiscus, Scopus, Korea Education and Research Information Service, Korean Studies Information Service System, Korean National Assembly Library, Research Information Sharing Service, National Digital Science Library, and China National Knowledge Infrastructure from their inception to December 2023. Two reviewers independently selected and extracted data from each study. We calculated effect sizes using a random-effects model with a 95 % confidence interval (CI) and evaluated study quality using the Physiotherapy Evidence Database scale. RESULTS: This review included ten studies with 227 participants aged 66.1-73.6 years. The meta-analysis revealed significant enhancements in cognitive function [Korean Version of Mini-Mental State Examination, standard mean difference (SMD) = 0.700, 95 % CI (0.364-1.037), I2 = 0 %, p < .001], blood indicators [ß-amyloid, SMD = 0.613, 95 % CI (0.103-1.123), I2 = 34.920 %, p < .05; brain-derived neurotrophic factor, SMD = 0.566, 95 % CI (0.166-0.966), I2 = 0 %, p < .01; high-density lipoprotein cholesterol, SMD = 0.677, 95 % CI (0.357-0.966), I2 = 0 %, p < .001; low-density lipoprotein cholesterol, SMD = 0.809, 95 % CI (0.376-1.242), I2 = 42.621 %, p < .001; and total cholesterol, SMD = 0.979, 95 % CI (0.603-1.356), I2 = 22.221 %, p < .001], and physical function [lean body mass, SMD = 0.465, 95 % CI (0.109-0.821), I2 = 0 %, p < .05, and handgrip strength, SMD = 0.929, 95 % CI (0.194-1.663), I2 = 48.217 %, p < .05]. CONCLUSIONS: This meta-analysis indicates that Taekwondo training is a beneficial therapy with protective effects on cognitive function, physical function, and body composition in older adults. These findings highlight its potential significance in cognitive rehabilitation and physiological health promotion among this demographic population.

Unraveling the interplay of temperature with molecular aggregation and miscibility in TEA-water mixtures.

In the phase diagram of binary liquid mixtures, a miscibility gap is found with the concomitant liquid-liquid phase separation, wherein temperature is a key parameter in modulating the phase behavior. This includes critical temperatures such as the lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Using a comprehensive approach including molecular dynamics (MD) simulation, graph theoretical analysis and spatial inhomogeneity measurement in an LCST-type mixture, we attempt to establish the relationship between the molecular aggregation pattern and phase behavior in TEA-water mixtures. At lower temperatures of binary liquid mixtures, TEA molecules tend to aggregate while simultaneously interacting with water forming a homogeneous solution. As the temperature increases, these TEA aggregates tend to self-associate by minimizing the interaction with water, which facilitates formation of two distinct liquid phases in the binary liquid. The spatial distribution analysis also reveals that the TEA aggregates compatible with water promote uniform distribution of water molecules, maintaining a homogeneous solution, while the water-incompatible ones generate isolation of water H-bond aggregates, leading to liquid-liquid phase separation in the binary system. This current study on temperature-induced molecular aggregation behavior is anticipated to contribute to a critical understanding of the phase behavior in binary liquid mixtures, including UCST, LCST, and reentrant phase behavior.

Photoprotective activities of Capsosiphon fulvescens in UVB-induced SKH-1 mice and human keratinocytes.

Capsosiphon fulvescens (CF) is a green alga widely consumed in East Asian countries, particularly in Korea. It has a rich composition of vitamins, minerals, dietary fibers, and bioactive compounds, which contribute to its multiple therapeutic properties. Its application ranges from acting as an antioxidant and anti-inflammatory agent to supporting the skin system. Despite these benefits of CF, the effects and mechanisms of action related to photoaging of the skin have not yet been elucidated. To investigate the photoprotective effects of CF against photoaging, both animal (SKH-1 mouse) and cell models (HaCaT cell line) were used in this study. As a result, administering the CF extract over a period of 10 weeks, which included times of Ultraviolet B (UVB) exposure, significantly reduced erythema and various UVB-induced skin changes, such as wrinkle formation, and the thickening of the epidermis and dermis, as well as alterations in the length and depth of wrinkles. Furthermore, our investigation into CF extract's antiwrinkle properties revealed its efficacy in enhancing skin hydration and collagen content, counteracting the collagen depletion and moisture loss induced by UVB radiation. Also, the fact that the levels of p-ERK, p-p38, and p-JNK proteins went down shows that the CF extract might have a controlling effect on the MAPK signaling pathways. Our findings suggest that CF holds significant potential for preventing photoaging, providing a foundation for the development of functional foods or botanical drugs targeting skin aging and related skin disorders. PRACTICAL APPLICATION: This research proved that Capsosiphon fulvescen, a green alga widely consumed in East Asian countries, provides photoprotective activities against UV-induced skin aging. Therefore, Capsosiphon fulvescen can be utilized as functional foods or botanical drugs targeting skin aging and related skin disorders.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Comparison of face mask effects on cardiorespiratory responses between physically active and sedentary individuals.

BACKGROUND: Alterations caused by face masks on physiological responses vary among different population groups. This study aimed to investigate whether physically active and sedentary individuals respond differently to face mask use during exercise. METHODS: Sixteen healthy college students were divided into two groups: Physically active group (N.=10; 26.50±2.80 years) and Sedentary group (N.=6; 26.33±2.81 years). They performed three maximal cardiopulmonary exercise test (CPET)s following the Bruce protocol: one without a face mask (NON), one with a surgical mask (SUR) and one with a cloth mask (CLO). Cardiorespiratory parameters and heart rate were monitored continuously during the test. Blood pressure, oxygen saturation and lactate level were measured immediately before and after exertion. RESULTS: Significant differences were found between the Physically active and the Sedentary group in peak VO2 (VO2peak) in NON (P=0.030). However, this difference disappeared when the face masks were used. Furthermore, VO2/kg (P=0.002) and METs (P=0.002) decreased significantly at the respiratory compensation point (RCP) only in the Physically active group with face masks. No significant differences were found between the two groups for exercise time, lactate level and dyspnea (P>0.05). CONCLUSIONS: The decrease in exercise tolerance and cardiorespiratory responses, particularly VO2peak, due to face mask use was greater in physically active individuals compared to sedentary individuals. Population group characteristics should be considered when adapting face masks to daily life.

Neural network model for prediction of possible sarcopenic obesity using Korean national fitness award data (2010-2023).

Sarcopenic obesity (SO) is characterized by concomitant sarcopenia and obesity and presents a high risk of disability, morbidity, and mortality among older adults. However, predictions based on sequential neural network SO studies and the relationship between physical fitness factors and SO are lacking. This study aimed to develop a predictive model for SO in older adults by focusing on physical fitness factors. A comprehensive dataset of older Korean adults participating in national fitness programs was analyzed using sequential neural networks. Appendicular skeletal muscle/body weight was defined as SO using an anthropometric equation. Independent variables included body fat (BF, %), waist circumference, systolic and diastolic blood pressure, and various physical fitness factors. The dependent variable was a binary outcome (possible SO vs normal). We analyzed hyperparameter tuning and stratified K-fold validation to optimize a predictive model. The prevalence of SO was significantly higher in women (13.81%) than in men, highlighting sex-specific differences. The optimized neural network model and Shapley Additive Explanations analysis demonstrated a high validation accuracy of 93.1%, with BF% and absolute grip strength emerging as the most influential predictors of SO. This study presents a highly accurate predictive model for SO in older adults, emphasizing the critical roles of BF% and absolute grip strength. We identified BF, absolute grip strength, and sit-and-reach as key SO predictors. Our findings underscore the sex-specific nature of SO and the importance of physical fitness factors in its prediction.

Diminished Immune Cell Adhesion in Hypoimmune ICAM-1 Knockout Pluripotent Stem Cells.

Hypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g., T cell) immune responses, but have largely not addressed the innate immune cells (e.g., monocytes, neutrophils) that mediate inflammation and rejection processes occurring early after graft transplantation. We identified the adhesion molecule ICAM-1 as a novel hypoimmune target that plays multiple critical roles in both adaptive and innate immune responses post-transplantation. In a series of studies, we found that ICAM-1 blocking or knock-out (KO) in hPSC-derived cardiovascular therapies imparted significantly diminished binding of multiple immune cell types. ICAM-1 KO resulted in diminished T cell proliferation responses in vitro and in longer in vivo retention/protection of KO grafts following immune cell encounter in NeoThy humanized mice. The ICAM-1 KO edit was also introduced into existing first-generation hypoimmune hPSCs and prevented immune cell binding, thereby enhancing the overall hypoimmune capacity of the cells. This novel hypoimmune editing strategy has the potential to improve the long-term efficacy and safety profiles of regenerative therapies for cardiovascular pathologies and a number of other diseases.

Characterization of high Zn content Cd0.87Zn0.13Te0.98Se0.02 grown using Bridgman technique.

CdZnTe (CZT) is a promising commercial material used as a room-temperature operating semiconductor detector for gamma-ray detection. Recently, CdZnTeSe (CZTS) detectors improved upon the properties of CZT by improving homogeneity and reducing defect properties, thereby enabling higher production yield of high-quality crystals. However, addition of selenium to CZT will reduce the bandgap and increase the amount of thermally stimulated electrons, resulting in low resistivity of the crystal. In this study, the enhancement of zinc content was introduced to compensate the bandgap reduction owing to selenium addition, while maintaining the improved properties of selenium addition. The morphology and stoichiometry of CZTS were determined using scanning electron microscopy and electron probe micro-analyzer. Furthermore, the calculated bandgap with stoichiometry was compared with the measured bandgap using UV-Vis measurement and Tauc plot. The electrical, chemical, and other spectroscopic properties were characterized using an I-V curve, X-ray photoelectron spectroscopy, and gamma-spectroscopic techniques, respectively. Moreover, it was proven that the high zinc CZTS can exhibit superior properties owing to selenium addition without affecting the bandgap reduction.

Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction.

Background: Although left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI. Methods: In a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated. Results: Among the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p < 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms-226.3 ms, p < 0.001) and LV elastance index (Ed; 0.133 1/ml-0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes. Conclusions: In patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Highly visible-light-active sulfur and carbon co-doped TiO2 (SC-TiO2) heterogeneous photocatalysts prepared by underwater discharge plasma.

To promptly and simply create highly crystalline S/C co-doped TiO2 (SC-TiO2) photocatalysts at room temperature and atmospheric pressure, we suggest a novel plasma-assisted sol-gel synthesis method. This method is a simultaneous synthetic process, in which an underwater plasma undergoes continuous reactions to generate high-energy atomic and molecular species that enable TiO2 to achieve crystallinity, a large surface area, and a heterogeneous structure within a few minutes. In particular, it was demonstrated that the heterogeneously structured TiO2 was formed by doping that sulfur and carbon replace O or Ti atoms in the TiO2 lattice depending on the composition of the synthesis solution during underwater plasma treatment. The resultant SC-TiO2 photocatalysts had narrowed bandgap energies and extended optical absorption scope into the visible range by inducing the intermediate states within bandgap due to generation of oxygen vacancies on the surface of TiO2 through synthesis, crystallization, and doping. Correspondingly, SC-TiO2 showed a significant degradation efficiency ([k] = 6.91 h-1) of tetracycline (TC, antibiotics) under solar light irradiation, up to approximately 4 times higher compared to commercial TiO2 ([k] = 1.68 h-1), resulting in great water purification. Therefore, we anticipate that this underwater discharge plasma system will prove to be an advantageous technique for producing heterostructural TiO2 photocatalysts with superior photocatalytic efficiency for environmental applications.

Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.

Molecular Aggregation Behavior and Microscopic Heterogeneity in Binary Osmolyte-Water Solutions.

Osmolytes, small organic compounds, play a key role in modulating the protein stability in aqueous solutions, but the operating mechanism of the osmolyte remains inconclusive. Here, we attempt to clarify the mode of osmolyte action by quantitatively estimating the microheterogeneity of osmolyte-water mixtures with the aid of molecular dynamics simulation, graph theoretical analysis, and spatial distribution measurement in the four osmolyte solutions of trimethylamine-N-oxide (TMAO), tetramethylurea (TMU), dimethyl sulfoxide, and urea. TMAO, acting as a protecting osmolyte, tends to remain isolated with no formation of osmolyte aggregates while preferentially interacting with water, but there is a strong aggregation propensity in the denaturant TMU solution, characterized by favored hydrophobic interactions between TMU molecules. Taken together, the mechanism of osmolyte action on protein stability is proposed as a comprehensive one that encompasses the direct interactions between osmolytes and proteins and indirect interactions through the regulation of water properties in the osmolyte-water mixtures.

Ulmus macrocarpa Hance trunk bark extracts inhibit RANKL-induced osteoclast differentiation and prevent ovariectomy-induced osteoporosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UmH) bark has been traditionally utilized for medicinal purposes. The bark extract of this plant has diverse health benefits, and its potential role in enhancing bone health is of distinct interest, particularly when considering the substantial health and economic implications of bone-related pathologies, such as osteoporosis. Despite the compelling theoretical implications of UmH bark in fortifying bone health, no definitive evidence at the in vivo level is currently available, thus highlighting the innovative and as-yet-unexplored potential of this field of study. AIM OF THE STUDY: Primarily, our study aims to conduct a meticulous analysis of the disparity in the concentration of active compounds in the UmH root bark (Umrb) and trunk bark (Umtb) extracts and confirm UmH bark's efficacy in enhancing bone health in vivo, illuminating the cellular mechanisms involved. MATERIALS AND METHODS: The Umrb and Umtb extracts were subjected to component analysis using high-performance liquid chromatography and then assessed for their inhibitory effects on osteoclast differentiation through the TRAP assay. An ovariectomized (OVX) mouse model replicates postmenopausal conditions commonly associated with osteoporosis. Micro-CT was used to analyze bone structure parameters, and enzyme-linked immunosorbent assay and staining were used to assess bone formation markers and osteoclast activity. Furthermore, this study investigated the impact of the extract on the expression of pivotal proteins and genes involved in bone formation and resorption using mouse bone marrow-derived macrophages (BMMs). RESULTS: The findings of our study reveal a significant discrepancy in the concentration of active constituents between Umrb and Umtb, establishing Umtb as a superior source for promoting bone health. I addition, a standardized pilot-scale procedure was conducted for credibility. The bone health benefits of Umtb were verified using an OVX model. This validation involved the assessment of various parameters, including BMD, BV/TV, and BS/TV, using micro-CT imaging. Additionally, the activation of osteoblasts was evaluated by Umtb by measuring specific factors such as ALP, OCN, OPG in blood samples and through IHC staining. In the same investigations, diminished levels of osteoclast differentiation factors, such as TRAP, NFATc1, were also observed. The observed patterns exhibited consistency in vitro BMM investigations. CONCLUSIONS: Through verification at both in vitro levels using BMMs and in vivo levels using the OVX-induced mouse model, our research demonstrates that Umtb is a more effective means of improving bone health in comparison to Umrb. These findings pave the way for developing health-functional foods or botanical drugs targeting osteoporosis and other bone-related disorders and enhance the prospects for future research extensions, including clinical studies, in extract applications.

Time-resolved photoluminescence analysis of ceramic Ce:GAGG scintillators.

This paper introduces the characteristics and efficiency of post-treatment methods for enhancing the timing resolution of ceramic Ce:GAGG scintillators. The thermal annealing and surface treatments were included to analyze their impact on time-resolved photoluminescence (TRPL) and thermoluminescence (TL) characteristics. Optical properties were improved by suppressing nonradiative recombination due to the reduced surface defects, while heat-treatment removes traps as confirmed by TL measurements. TRPL decay characteristics revealed that samples treated with mechanical polishing followed by heat treatment exhibited the best scintillation performance, with a slow component of 272.3 ns. These findings will aid in developing techniques for improving the luminescence of other inorganic scintillators.

PRID: Prediction Model Using RWR for Interactions between Drugs.

Drug-drug interactions (DDI) occur because of the unexpected pharmacological effects of drug pairs. Although drug efficacy can be improved by taking two or more drugs in the short term, this may cause inevitable side effects. Currently, multiple drugs are prescribed based on the experience or knowledge of the clinician, and there is no standard database that can be referred to as safe co-prescriptions. Thus, accurately identifying DDI is critical for patient safety and treatment modalities. Many computational methods have been developed to predict DDIs based on chemical structures or biological features, such as target genes or functional mechanisms. However, some features are only available for certain drugs, and their pathological mechanisms cannot be fully employed to predict DDIs by considering the direct overlap of target genes. In this study, we propose a novel deep learning model to predict DDIs by utilizing chemical structure similarity and protein-protein interaction (PPI) information among drug-binding proteins, such as carriers, transporters, enzymes, and targets (CTET) proteins. We applied the random walk with restart (RWR) algorithm to propagate drug CTET proteins across a PPI network derived from the STRING database, which will lead to the successful incorporation of the hidden biological mechanisms between CTET proteins and disease-associated genes. We confirmed that the RWR propagation of CTET proteins helps predict DDIs by utilizing indirectly co-regulated biological mechanisms. Our method identified the known DDIs between clinically proven epilepsy drugs. Our results demonstrated the effectiveness of PRID in predicting DDIs in known drug combinations as well as unknown drug pairs. PRID could be helpful in identifying novel DDIs and associated pharmacological mechanisms to cause the DDIs.

Risk Factors and Outcomes With Progressive Mitral Annular Calcification.

Background Mitral annular calcification (MAC) is a chronic degenerative process that may progress. This study aimed to investigate associating factors and clinical implications of MAC progression. Methods and Results Among 560 patients with MAC identified by transthoracic echocardiography between January 2012 and June 2016, 138 patients (mean±SD age 72.7±10.2 years, 73 women) with mild or moderate MAC who received follow-up examination within 18 to 36 months were retrospectively analyzed. Progressive MAC was defined as hemodynamic or structural profiles that had worsened by more than 1 grade. Hemodynamic features were assessed by the transmitral mean diastolic pressure gradient (MDPG), and structural features were assessed by the MAC angle in the parasternal short-axis view. The clinical outcome was defined as a composite of all-cause mortality, hospitalization for heart failure, and occurrence of ischemic stroke. Forty-three patients (31.2%) showed progressive MAC. Patients with progressive MAC had higher systolic blood pressure, pulse pressure, MAC angle, and MDPG than those with stable MAC. Patients with progressive MAC had smaller left ventricular (LV) end-systolic dimensions and higher LV ejection fractions compared with those with stable MAC. In multivariate analysis, pulse pressure, LV ejection fraction, MAC angle, and MDPG at baseline were significantly associated with MAC progression. During a median of 39.2 months' follow-up, patients with progressive MAC showed poorer clinical outcomes than those with stable MAC (log-rank P=0.015). Conclusions MAC progression is not rare and is associated with structural substrate and hemodynamic loads that result in mechanical stress. Patients with progressive MAC have poor outcomes.

Controlling the Chameleonic Behavior and Membrane Permeability of Cyclosporine Derivatives via Backbone and Side Chain Modifications.

Some macrocycles exhibit enhanced membrane permeability through conformational switching in different environmental polarities, a trait known as chameleonic behavior. In this study, we demonstrate specific backbone and side chain modifications that can control chameleonic behavior and passive membrane permeability using a cyclosporin O (CsO) scaffold. To quantify chameleonic behavior, we used a ratio of the population of the closed conformation obtained in polar solvent and nonpolar solvent for each CsO derivative. We found that ß-hydroxylation at position 1 (1 and 3) can encode chameleonicity and improve permeability. However, the conformational stabilization induced by adding an additional transannular H-bond (2 and 5) leads to a much slower rate of membrane permeation. Our CsO scaffold provides a platform for the systematic study of the relationship among conformation, membrane permeability, solubility, and protein binding. This knowledge contributes to the discovery of potent beyond the rule of five (bRo5) macrocycles capable of targeting undruggable targets.