Rotundifuran Induces Ferroptotic Cell Death and Mitochondria Permeability Transition in Lung Cancer Cells.

Rotundifuran (RF), a potent anti-inflammatory and anti-cancer compound, is a natural compound predominantly present in Vitex Rotundifolia. Herein, we investigated the effects of RF on the growth of lung cancer cells. Our findings suggested that RF inhibits cell growth, highlighting its potential as a therapeutic agent for cancer treatment. Interestingly, we observed that cell growth inhibition was not due to apoptosis, as caspases were not activated and DNA fragmentation did not occur. Furthermore, we found that intracellular vacuoles and autophagy were induced, but RF-induced cell death was not affected when autophagy was inhibited. This prompted us to investigate other possible mechanisms underlying cell growth inhibition. Through a cDNA chip analysis, we confirmed changes in the expression of ferroptosis-related genes and observed lipid peroxidation. We further examined the effect of ferroptosis inhibitors and found that they alleviated cell growth inhibition induced by RF. We also observed the involvement of calcium signaling, ROS accumulation, and JNK signaling in the induction of ferroptosis. Our findings suggested that RF is a potent anti-cancer drug and further studies are needed to validate its clinal use.

Metabolically Abnormal Non-Obese Phenotype Is Significantly Associated with All-Cause Mortality in Hemodialysis Patients.

The association between obesity and all-cause mortality in patients undergoing kidney failure with replacement therapy (KFRT) has shown conflicting results. This study aimed to evaluate whether metabolic abnormalities (MA) increase the risk of all-cause mortality in these patients. Between 2009 and 2015, 1141 patients undergoing KFRT were recruited from the Clinical Research Center for End-Stage Renal Disease dataset. Patients were divided into four groups according to the presence of obesity and MA. Multivariate Cox proportional hazard analysis was performed to determine the association between the phenotypes and all-cause mortality. During a mean follow-up of 4.2 years, all-cause mortality was observed in 491 (43.0%) patients. Obesity had a 24% decreased risk of all-cause mortality compared with non-obesity. In contrast, the presence of MA showed a 1.53-fold increased risk of all-cause mortality. There was a significant interaction between obesity and MA (p = 0.006). In Cox proportional hazard analyses after adjustment of confounding factors, the metabolically abnormal non-obesity (MANO) phenotype showed a 1.63-fold increased risk of all-cause mortality compared with the metabolically healthy non-obesity phenotype. In subgroup analysis, the risk of all-cause mortality was higher in the MANO phenotype; this phenotype was significantly associated with a higher all-cause mortality in patients undergoing KFRT.

Rex1BD and the 14-3-3 protein control heterochromatin organization at tandem repeats by linking RNAi and HDAC.

Tandem DNA repeats are often organized into heterochromatin that is crucial for genome organization and stability. Recent studies revealed that individual repeats within tandem DNA repeats can behave very differently. How DNA repeats are assembled into distinct heterochromatin structures remains poorly understood. Here, we developed a genome-wide genetic screen using a reporter gene at different units in a repeat array. This screen led to identification of a conserved protein Rex1BD required for heterochromatin silencing. Our structural analysis revealed that Rex1BD forms a four-helix bundle structure with a distinct charged electrostatic surface. Mechanistically, Rex1BD facilitates the recruitment of Clr6 histone deacetylase (HDAC) by interacting with histones. Interestingly, Rex1BD also interacts with the 14-3-3 protein Rad25, which is responsible for recruiting the RITS (RNA-induced transcriptional silencing) complex to DNA repeats. Our results suggest that coordinated action of Rex1BD and Rad25 mediates formation of distinct heterochromatin structure at DNA repeats via linking RNAi and HDAC pathways.

Infrastructure in the Age of Pandemics: Utilizing Polypropylene-Based Mask Waste for Durable and Sustainable Road Pavements.

When navigating the environmental exigencies precipitated by global pandemics, the escalation of mask waste presents a multifaceted dilemma. In this avant-garde research, we unveil a novel approach: harnessing the sterilized shredded mask residues (SMRs), predominantly composed of 100 wt. % polypropylene, as pioneering modifiers for asphalt. Distinct proportions of SMR (e.g., 3, 6, and 9 wt. %) were judiciously integrated with fresh-virgin base AP-5 asphalt and subjected to an extensive suite of state-of-the-art examinations, encompassing thin-layer chromatography-flame ionization detection (TLC-FID), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and specific rheological metrics. The TLC-FID diagnostic trajectories highlighted the nuanced rejuvenating influence of SMR on the binder, a facet reinforced by a pronounced elevation in the thermodynamic stability index (IC). The FT-IR spectra elucidated SMR's preeminent role as a filler, negating notions of chemical reactivity. The TGA analyses unveiled an elevated thermal onset of degradation, signposting enhanced thermal resilience, whereas the DSC readings illuminated a superior thermal comportment at lower extremities. The SEM evaluations rendered a clearer panorama: there was heightened textural perturbation at escalated SMR incorporations, yet the 3 wt. % concoction showcased an optimal, coherent microtexture symbiosis with asphalt. The rheological scrutinies revealed a systematic trajectory: a diminishing penetration and ductility countered by ascending softening points and viscosity metrics. The coup de maître stemmed from the DSR analyses, unequivocally validating SMR's unparalleled prowess in curtailing rutting distress. This seminal inquiry not only posits a blueprint for refined pavement longevity but also champions a sustainable countermeasure to pandemic-propelled waste, epitomizing the confluence of environmental prudence an d infrastructural fortitude.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

From Hive to Highway: Waste Honeycombs as a Sustainable Modifier for Asphalt Binder Formulations in South Korea.

Navigating the crossroads of sustainable infrastructure and innovative waste management, this research unveils the potential of waste honeycombs (WHCs)-an overlooked byproduct of apiculture-as a potent modifier for asphalt binder formulations. This endeavor addresses the dual challenge of enhancing road pavement sustainability and mitigating environmental degradation. A meticulous methodology evaluated the impact of varying WHC concentrations (5, 10, and 15 wt.%) on the asphalt binder, examining its attributes pre- and post-aging. Employing an array of analytical tools-thin-layer chromatography-flame ionization detection (TLC-FID); Fourier transform-infrared spectroscopy (FT-IR); scanning electron microscopy (SEM); thermogravimetric analysis (TGA); and a suite of conventional tests such as penetration, softening point, viscosity, ductility, dynamic shear rheometer (DSR), and multiple stress-creep recovery (MSCR)-provided a comprehensive insight into the binder's behavior. TLC-FID analyses revealed that WHC, with its 92 wt.% resin content, altered the SARA profile across distinct aging conditions, notably reducing asphaltene content, a factor linked to binder stiffness. The colloidal instability index (IC) further attested to this, pointing to a more thermodynamically stable system with WHC's inclusion. Meanwhile, FT-IR confirmed a physical interaction between WHC and asphalt without introducing new chemical entities. SEM observations highlighted the superior miscibility of WHC with asphalt, evidenced by a unique microtexture. With marked precision, TGA assessments unveiled a bolstering of asphalt's inherent thermal resilience consequent to a minor WHC integration. From the conventional tests, shifts in penetration, softening point, and viscosity were observed, with reduced viscosity, indicating improved workability. Lastly, while rutting potential was sensitive to WHC concentrations, fatigue resistance notably heightened with minor to moderate WHC inclusions. In essence, this pioneering study advocates for WHC's integration into asphalt formulations, offering enhanced road performance coupled with sustainable waste utilization. The findings underscore the synergy between environmental stewardship and infrastructural advancement.

Methyl lucidone inhibits airway inflammatory response by reducing TAK1 activity in human bronchial epithelial NCI-H292 cells.

Background: Methyl lucidone (ML), a methyl derivative of lucidone, has anti-inflammatory properties. However, the molecular mechanisms that reduce the inflammatory effect of ML in human lung epithelial cells remain unkown. This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory effect of ML. Methods: Four compounds (ML, methyl linderone, kanakugiol, and linderone) from Lindera erythrocarpa Makino were evaluated for their ability to reduce MUC5AC secretion levels in phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells using ELISA. The expression and secretion levels of inflammatory response-related proteins were analyzed using quantitative reverse transcription-PCR, ELISA, and western blotting. To determine whether ML directly regulates TGF-ß-activated kinase 1 (TAK1), we performed an in vitro kinase assay. Results: ML treatment effectively reduced the levels of inflammatory cytokines, including interleukin-1ß and TNF-α, increased by stimulation. Furthermore, ML downregulated the pathway cascade of both IκB kinase (IKK)/NF-κB and p38 mitogen-activated protein (MAP) kinase/CREB by inhibiting the upstream kinase TAK1. An in vitro kinase analysis confirmed that ML treatment significantly reduced the kinase activity of TAK1. Conclusion: ML pretreatment repressed the PMA-stimulated inflammation reaction by reducing the TAK1-mediated IKK/NF-κB and p38 MAP kinase/CREB signaling. These findings suggest that ML may improve respiratory health and can be used as a dietary supplement or functional food to prevent inflammatory lung diseases.

Clinical and Genetic Features of Korean Inherited Arrhythmia Probands.

BACKGROUND AND OBJECTIVES: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. METHODS: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. RESULTS: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). CONCLUSIONS: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). METHODS: This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. RESULTS: Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. CONCLUSION: We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

The impact of severe depression on the survival of older patients with end-stage kidney disease.

Background: Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01-1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.

Molecular Dynamics Simulation Study of the Protonation State Dependence of Glutamic Acid Transport through a Cyclic Peptide Nanotube.

The effect of the protonation state of glutamic acid on its translocation through cyclic peptide nanotubes (CPNs) was assessed by using molecular dynamics (MD) simulations. Anionic (GLU-), neutral zwitterionic (GLU0), and cationic (GLU+) forms of glutamic acid were selected as three different protonation states for an analysis of energetics and diffusivity for acid transport across a cyclic decapeptide nanotube. Based on the solubility-diffusion model, permeability coefficients for the three protonation states of the acid were calculated and compared with experimental results for CPN-mediated glutamate transport through CPNs. Potential of mean force (PMF) calculations reveal that, due to the cation-selective nature of the lumen of CPNs, GLU-, so-called glutamate, shows significantly high free energy barriers, while GLU+ displays deep energy wells and GLU0 has mild free energy barriers and wells inside the CPN. The considerable energy barriers for GLU- inside CPNs are mainly attributed to unfavorable interactions with DMPC bilayers and CPNs and are reduced by favorable interactions with channel water molecules through attractive electrostatic interactions and hydrogen bonding. Unlike the distinct PMF curves, position-dependent diffusion coefficient profiles exhibit comparable frictional behaviors regardless of the charge status of three protonation states due to similar confined environments imposed by the lumen of the CPN. The calculated permeability coefficients for the three protonation states clearly demonstrate that glutamic acid has a strong protonation state dependence for its transport through CPNs, as determined by the energetics rather than the diffusivity of the protonation state. In addition, the permeability coefficients also imply that GLU- is unlikely to pass through a CPN due to the high energy barriers inside the CPN, which is in disagreement with experimental measurements, where a considerable amount of glutamate permeating through the CPN was detected. To resolve the discrepancy between this work and the experimental observations, several possibilities are proposed, including a large concentration gradient of glutamate between the inside and outside of lipid vesicles and bilayers in the experiments, the glutamate activity difference between our MD simulations and experiments, an overestimation of energy barriers due to the artifacts imposed in MD simulations, and/or finally a transformation of the protonation state from GLU- to GLU0 to reduce the energy barriers. Overall, our study demonstrates that the protonation state of glutamic acid has a strong effect on the transport of the acid and suggests a possible protonation state change for glutamate permeating through CPNs.

Influence of Mix Design on Physical, Mechanical and Durability Properties of Multi-Recycled Aggregate Concrete.

The decrease in the quality of recycled aggregate due to an increase in the number of recycling is a primary factor that limits the multi-recycling of concrete. This degradation adversely affects concrete performance; thus, the characteristics of recycled aggregate should be considered during the mix design stage, but little research has taken that into account. This study investigates the effect of the equivalent mortar volume (EMV) mix design on some physical, mechanical and durability properties of concrete made of multiple recycled coarse aggregates at 50% and 100% replacement ratios compared to concrete made by the conventional mix design (CMD). The results showed that the performances of concrete by the CMD decreased with an increasing number of recycling cycles. The properties of EMV-based concrete deteriorated with an increase in the number of recycling cycles at 100% replacement ratio due to poor workability caused by a shortage of fresh mortar. However, at 50% replacement, the EMV-based concrete exhibited similar performance across the three cycles of recycling, as well as improved properties over natural aggregate concrete. This study demonstrated that an appropriate mix design and optimal aggregate replacement ratio can offset the property loss of multiple recycled aggregate concrete.

The benefit of planned dialysis to early survival on hemodialysis versus peritoneal dialysis: a nationwide prospective multicenter study in Korea.

Optimal preparation is recommended for patients with advanced chronic kidney disease to minimize complications during dialysis initiation. This study evaluated the effects of planned dialysis initiation on survival in patients undergoing incident hemodialysis and peritoneal dialysis. Patients newly diagnosed with end-stage kidney disease who started dialysis were enrolled in a multicenter prospective cohort study in Korea. Planned dialysis was defined as dialysis therapy initiated with permanent access and maintenance of the initial dialysis modality. A total of 2892 patients were followed up for a mean duration of 71.9 ± 36.7 months and 1280 (44.3%) patients initiated planned dialysis. The planned dialysis group showed lower mortality than the unplanned dialysis group during the 1st and 2nd years after dialysis initiation (1st year: adjusted hazard ratio [aHR] 0.51; 95% confidence interval [CI] 0.37-0.72; P < 0.001; 2nd year: aHR 0.71; 95% CI 0.52-0.98, P = 0.037). However, 2 years after dialysis initiation, mortality did not differ between the groups. Planned dialysis showed a better early survival rate in hemodialysis patients, but not in peritoneal dialysis patients. Particularly, infection-related mortality was reduced only in patients undergoing hemodialysis with planned dialysis initiation. Planned dialysis has survival benefits over unplanned dialysis in the first 2 years after dialysis initiation, especially in patients undergoing hemodialysis. It improved infection-related mortality during the early dialysis period.

WavelNet: A novel convolutional neural network architecture for arrhythmia classification from electrocardiograms.

BACKGROUND AND OBJECTIVE: Automated detection of arrhythmias from electrocardiograms (ECGs) can be of considerable assistance to medical professionals in providing efficient treatment for patients with cardiovascular diseases. In recent times, convolutional neural network (CNN)-based arrhythmia classification models have been introduced, but their decision-making processes remain unclear and their performances are not reproducible. This paper proposes an accurate, interpretable, and reproducible end-to-end arrhythmia classification model based on a novel CNN architecture named WavelNet, which is interpretable and optimal for dealing with ECGs. METHODS: Inspired by SincNet, which is capable of band-pass filtering-based spectral analysis, WavelNet was devised to achieve wavelet transform-based spectral analysis. WavelNet was trained using a subject-oriented five-class ECG arrhythmia dataset generated from the MIT-BIH Arrhythmia Database while following a benchmark scheme. By adopting various mother wavelets, multiple WavelNet-based arrhythmia classification models were implemented. To investigate whether our wavelet transform-based approach outperforms original end-to-end and band-pass filtering-based approaches, our proposed models were compared with vanilla CNN- and SincNet-based models. Model implementation and evaluation processes were repeated ten times in a Google Colab Pro+ environment. Furthermore, our most successful model was compared with state-of-the-art arrhythmia classification models for performance evaluation. RESULTS: The proposed WavelNet-based models showed excellent performance on classifying non-ectopic, supraventricular ectopic, and ventricular ectopic beats because of their ability to perform adaptive spectral analysis while preserving temporal ECG information compared with vanilla CNN- and SincNet-based models. In particular, a Symlet 4 wavelet-adopting WavelNet-based model achieved the best performance with nearly 90% overall accuracy as well as the highest levels of sensitivity in classifying each arrhythmia class: 91.4%, 49.3%, and 91.4% for non-ectopic, supraventricular ectopic, and ventricular ectopic beat classifications, respectively. These results were comparable to those of state-of-the-art models. In addition, the results are reproducible, which differentiates our study from previous studies. CONCLUSIONS: Our proposed WavelNet-based arrhythmia classification model achieved remarkable performance based on a reasonable decision-making process, in comparison with other models. As its noteworthy performance is clinically reasonable and reproducible, our proposed model can contribute toward implementing a real-world precision healthcare system for patients with cardiovascular diseases.

Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea.

BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Sex disparities in mortality among patients with kidney failure receiving dialysis.

Females are known to have a better survival rate than males in the general population, but previous studies have shown that this superior survival is diminished in patients on dialysis. This study aimed to investigate the risk of mortality in relation to sex among Korean patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). A total of 4994 patients with kidney failure who were receiving dialysis were included for a prospective nationwide cohort study. Cox multivariate proportional hazard models were used to determine the association between sex and the risk of cause-specific mortality according to dialysis modality. During a median follow-up of 5.8 years, the death rate per 100 person-years was 6.4 and 8.3 in females and males, respectively. The female-to-male mortality rate in patients on dialysis was 0.77, compared to 0.85 in the general population. In adjusted analyses, the risk of all-cause mortality was significantly lower for females than males in the entire population (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.87, P < 0.001). No significant differences in the risk of cardiovascular and infection-related deaths were observed according to sex. The risk of mortality due to sudden death, cancer, other, or unknown causes was significantly lower for females than males in the entire population (HR 0.66, 95% CI 0.56-0.78, P < 0.001), in patients on HD (HR 0.75, 95% CI 0.62-0.90, P = 0.003), and in patients on PD (HR 0.49, 95% CI 0.34-0.70, P < 0.001). The survival advantage of females in the general population was maintained in Korean dialysis patients, which was attributed to a lower risk of noncardiovascular and noninfectious death.Trial registration: ClinicalTrials.gov Identifier: NCT00931970.

Factors Affecting Selection of a Dialysis Modality in Elderly Patients With Chronic Kidney Disease: A Prospective Cohort Study in Korea.

Background: We investigated factors associated with the selection of a dialysis modality for elderly patients compared to younger patients. Methods: This study included 2,514 incident dialysis patients from a Korean multicenter prospective cohort. Multivariate logistic regression analyses were performed with demographic, socioeconomic, and clinical data to analyze factors associated with the chosen dialysis modality. Differences in these factors were compared between the elderly (≥65 years) and younger (<65 years) patients. Results: Of the enrolled patients, 1,746 (69.5%) and 768 (30.6%) selected hemodialysis (HD) and peritoneal dialysis (PD), respectively. The percentage of PD was higher in younger patients than in elderly patients (37.1 vs. 16.9%, p < 0.001). Multivariate analysis showed that planned dialysis (p < 0.001), employment status (p < 0.001), and independent economic status (p = 0.048) were independent factors for selecting PD, whereas peripheral vascular disease (p = 0.038) and tumor (p = 0.010) were factors for selecting HD in the younger group. In the elderly group, planned dialysis (p < 0.001) and congestive heart failure (CHF; p = 0.002) were associated with choosing PD; however, tumor (p = 0.006) was associated with choosing HD. A two-way ANOVA showed that planned dialysis and CHF showed a significant interaction effect with age on modality selection. Conclusions: As the age of patients with chronic kidney disease increased, HD was more frequently selected compared to PD. Dialysis planning and CHF interacted with age in selecting dialysis modalities in elderly patients. Elderly patients were less affected by socioeconomic status than younger patients.

Upcycling Discarded Shoe Polish into High Value-Added Asphalt Fluxing Agent for Use in Hot Mix Paving Applications.

This research effort is geared towards revealing the latent potential of discarded shoe polish that might be repurposed as an asphalt fluxing agent for the construction of durable and sustainable road surfaces. To drive this creative invention, the effect of various proportions of waste shoe polish (e.g., 5, 10 and 15 wt. % WSP) on the performance of base AP-5 bitumen was inspected in great detail. A meticulous investigation of the chemical, physical, and rheological properties of the resultant combinations was carried out using a variety of state-of-the-art laboratory techniques, specifically: thin-layer chromatography-flame ionization detection (TLC-FID), Fourier transform-infrared spectroscopy (FT-IR), needle penetration, ring-and-ball softening point, Brookfield viscometer, ductility, flash/fire points, dynamic shear rheometer (DSR), multiple stress-creep recovery (MSCR), and bending beam rheometer (BBR) tests. The Iatroscan data disclosed that the continuous feeding of binder with WSP had a minor impact on SARA fractional distribution, regardless of aging. According to the FT-IR scan, the stepwise addition of WSP to the binder did not result in any significant chemical alterations in the blends. The combined outcomes of the DSR/BBR/empirical test methods forecasted that the partly bio-sourced additive would greatly improve the mixing-compaction temperatures, workability, and coating-adhesion properties of bituminous mixtures while imparting them with outstanding anti-aging/cracking attributes. In short, the utilization of waste shoe polish as a fluxing agent for hot asphalt mix production and application is not only safe, feasible, and affordable, but it has the potential to abate the pollution caused by the shoe-care market while simultaneously enhancing the overall performance of the pavement and extending its service lifespan.

Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation.

Biosynthesis of spinosyn A in Saccharopolyspora spinosa involves a 1,4-dehydration followed by an intramolecular [4 + 2]-cycloaddition catalyzed by SpnM and SpnF, respectively. The cycloaddition also takes place in the absence of SpnF leading to questions regarding its mechanism of catalysis and biosynthetic role. Substrate analogs were prepared with an unactivated dienophile or an acyclic structure and found to be unreactive consistent with the importance of these features for cyclization. The SpnM-catalyzed dehydration reaction was also found to yield a byproduct corresponding to the C11 = C12 cis isomer of the SpnF substrate. This byproduct is stable both in the presence and absence of SpnF; however, relative production of the SpnM product and byproduct could be shifted in favor of the former by including SpnF or the dehydrogenase SpnJ in the reaction. This result suggests a potential interplay between the enzymes of spinosyn A biosynthesis that may help to improve the efficiency of the pathway.