•Tuneability and recyclability of DESs as extraction media were demonstrated.•A new strategy to design a ternary DES was developed for maximal extraction efficiency.•Complete recovery of extracted ...ginsenosides from DES was achieved through SPE.•The developed method was much greener and more efficient than previous methods.
The present study demonstrates that deep eutectic solvents (DESs) with the highest extractability can be designed by combining effective DES components from screening diverse DESs. The extraction of polar ginseng saponins from white ginseng was used as a way to demonstrate the tuneability as well as recyclability of DESs. A newly designed ternary DES (GPS-5) composed of glycerol, l-proline, and sucrose at 9:4:1 was used as a sustainable and efficient extraction medium. Based on the anti-tumor activity on HCT-116 cancer cells, it was confirmed that GPS-5 was merely an extraction solvent with no influence of the bioactivity of the ginsenosides extracted. Excellent recovery of the extracted saponins was easily achieved through solid-phase extraction (SPE). Recycling of the DES was accomplished by simple freeze-drying of the washed solutions from the SPE. The extraction efficiencies of the DESs recycled once, twice, and thrice were 92%, 85%, and 83% of that of the freshly synthesized solvent.
In this study, we report the precise shape control of crystalline cerium oxide, whose morphology changes between nanorods and nanoparticles in a short time. The proposed synthetic route of cerium ...oxide nanorods was highly dependent on the reaction time, and 10 min was determined to be the optimum synthetic condition. The cerium oxide nanorods were further converted into nanoparticles by the spontaneous assembly of cerium oxide nanoparticles into nanorods. The transmission electron microscopy results showed that the synthesized nanorods grew with high crystallinity along the 〈110〉 direction. The cerium oxide nanorods have been proven to be very efficient electron mediators for use as excellent photocatalytic materials and highly sensitive chemical sensors. The chemical sensor fabricated on a carbon paper substrate showed the high sensitivity of 1.81 μA mM
cm
and the detection limit of 6.4 μM with the correlation coefficient of 0.950.
Head and neck cancers (HNC) are frequently associated with neurodegeneration. However, the association between HNC and Parkinson’s disease (PD) remains unclear. This study aimed to clarify the ...relationship between HNC and subsequent PD. This retrospective study used data from a nationally representative cohort. Patients with HNC were identified based on the presence of corresponding diagnostic codes. Participants without cancer were selected using 4:1 propensity score matching based on sociodemographic factors and year of enrollment; 2296 individuals without HNC and 574 individuals with HNC were included in the study. Hazard ratios (HR) for the incidence of PD in patients with HNC were calculated using 95% confidence intervals (CI). The incidence of PD was 4.17 and 2.18 per 1000 person-years in the HNC and control groups, respectively (adjusted HR = 1.89, 95% CI = 1.08–3.33). The HNC group also showed an increased risk of subsequent PD development. The risk of PD was higher in middle-aged (55–69 years) patients with HNC and oral cavity cancer. Our findings suggest that middle-aged patients with HNC have an increased incidence of PD, specifically those with oral cavity cancer. Therefore, our findings provide new insights into the development of PD in patients with HNC.
Aquatic vegetation plays an important role in maintaining the health of river ecosystems. However, few studies have evaluated the impact of vegetation decomposition on water quality in rivers. ...Therefore, we aimed to analyze the effect of aquatic vegetation decomposition on nutrient conditions in the Jeonjucheon River in South Korea. To this end, we determined the distribution and biomass of four dominant species: Phragmites japonica Steud., Phragmites australis (Cav.) Trin. ex Steud., Miscanthus sinensis Andersson, and Rumex crispus L. Additionally, we conducted a nutrient leaching experiment to determine the contributions of different species to the nutrient status of the river. We found that the decomposition concentrations of total nitrogen (TN) and total phosphorus (TP) were the highest for P. japonica (7.74 mg/L) and R. crispus (1.59 mg/L). The annual load of TN from decomposition was 536,171.6 kg/yr and that of TP was 57,547.1 kg/yr. The total pollution load for the Jeonjucheon River was 2,903,885.3 kg/yr for TN and 17,602.1 kg/yr for TP. However, the TN and TP contribution from vegetation decomposition was negligible compared to that from other sources. This study serves as a valuable reference for sustainable management of river vegetation and water pollution.
Multi-stage stamping process is the promising technology to fabricate the metallic bipolar plate (BPP) for proton exchange membrane (PEM) fuel cell. In the present study, a novel die design in the ...pre-forming stage is proposed and its effect on the formability of ultra-thin metallic BPP is verified by the finite element (FE) simulations of micro- and macro-scale BPP channels. It reveals that the multi-stage forming with the proposed die approach significantly improve the formability of ultra-thin BPP. As a result, the more uniform thickness distribution and considerable reduction of springback are beneficial to the fabrication of high quality metallic BPP. Furthermore, the relatively high reaction efficiency (∼79.4%) of fuel cell stacks can be predicted, indicating the high fuel consumption. These findings demonstrate the feasibility and efficiency of the proposed die design in the fabrication of ultra-thin metallic BPP based on the perspectives of both the formability and energy efficiency.
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•Novel die design for multi-stage stamping of ultra-thin metallic BPP is proposed.•It reveals more uniform thickness distribution in the micro- and macro-scale BPPs.•Springback and distortion behaviors are significantly reduced.•The high reaction efficiency of fuel cell stacks is predicted.•It demonstrates a noticeable formability improvement with the proposed die design.
•The combined CPFEM–MK model is developed for predicting forming limits of ultra-thin FSS bipolar plate.•Realistic RVEs are successfully generated by a hybrid cellular automata–Monte Carlo ...model.•Predicted forming limits with realistic RVE well agree with the experimental results.•Formability of ultra-thin FSS sheet significantly decreases with the increasing grain size.•Early plastic flow instability induced from the localized deformation at subsurface grain is responsible for the decrease of forming limit strains.
The present study investigated the size effect on the formability of ultra-thin metallic bipolar plate for proton exchange membrane (PEM) fuel cell by crystal plasticity finite element method (CPFEM) in conjunction with the Marciniak-Kuczynski (MK) model. Mechanical behavior and crystallographic texture of a 0.08 mm-thick ferritic stainless steel (FSS) sheet were characterized by uniaxial tensile test and electron backscatter diffraction (EBSD) measurement. Nakazima formability test was carried out to measure the forming limit diagram (FLD) of ultra-thin FSS sheet. A hybrid cellular automata–Monte Carlo (CA–MC) model was developed to generate a ‘realistic’ representative volume element (RVE) that accurately reconstructed the measured texture and grain boundary misorientation distribution (GBMD). The predicted FLD by the CPFEM–MK model with the realistic RVE shows a good agreement with the experimental results. In order to explore the size effect on the formability, the forming limit analyses were performed using RVEs with various thickness-to-grain size ratios (t/d = 2∼10). The results reveal a significant degradation of the formability of the ultra-thin FSS sheet as t/d decreases. With decreasing number of grains through the thickness, the stress and strain heterogeneities in the surface grains are noticeably increased due to the less constraint by the subsurface grains, which plays an important role in the size effect. Furthermore, it is found that the surface strain hot spots in the material with low t/d can act as the geometrical imperfection to accelerate the failure, together with the increased stress triaxiality in the surface grains as the results of the localized strains and premature necking during the deformation. This attributes the decrease of forming limit strains to the early plastic flow instability in the ultra-thin sheet material with low thickness-to-grain size ratio.
Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson's disease progression. Recent evidence suggests that inflammation plays an important role in the ...propagation of protein aggregates. However, the mechanism by which inflammation regulates the propagation of aggregates remains unknown. Here, using in vitro cultures, we found that soluble factors secreted from activated microglia promote cell-to-cell propagation of α-synuclein and further showed that among these soluble factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly, secretion of α-synuclein was increased in senescent neurons, reflecting acquisition of a senescence-associated secretory phenotype (SASP). Using vacuolin-1, an inhibitor of lysosomal exocytosis, and RNAi against rab27a, we demonstrated that the SASP was mediated by lysosomal exocytosis. Correlative light and electron microscopy and immunoelectron microscopy confirmed that propagating α-synuclein aggregates were present in electron-dense lysosome-like compartments. TNF-α promoted the SASP through stimulation of lysosomal exocytosis, thereby increasing the secretion of α-synuclein. Collectively, these results suggest that TNF-α is the major inflammatory factor that drives cell-to-cell propagation of α-synuclein by promoting the SASP and subsequent secretion of α-synuclein.
Several studies have demonstrated the harmful effects of chronic kidney disease (CKD) on the audiovestibular system. Through a time-to-event analysis, we aimed to compare the association of CKD with ...sudden sensorineural hearing loss (SSNHL), and Ménière's disease against a control population without CKD. We used a total of 1,025,340 patients from the Korean National Health Insurance Service database from 2002 to 2013. The CKD group (n = 2572) included patients diagnosed with CKD more than three times between January 2003 and December 2005. The non-CKD group (n = 5144) consisted of two patients without CKD for every patient with CKD. Each patient was monitored until December 2013. We calculated the incidence, survival rate, and hazards ratio (HR) of SSNHL and Ménière's disease. In the CKD group, the incidence of SSNHL and Ménière's disease was 1.39 and 3.64 per 1000 person-years, respectively. Patients with CKD showed an adjusted HR of 2.15 and 1.45 for SSNHL and Ménière's disease, respectively. Middle-aged patients with CKD were associated with a higher incidence of developing SSNHL and Ménière's disease than those without CKD. Female patients with CKD had a higher risk of developing SSNHL; however, there was no significant difference in the risk of Ménière's disease in patients with CKD according to sex. Our findings suggest that CKD is associated with an increased incidence of SSNHL and Ménière's disease. Therefore, audiovestibular surveillance should be considered in patients with CKD.
Objective
Thyroid hormone abnormalities have been linked to antiseizure medications (ASMs). Oxcarbazepine is considered safer than carbamazepine because it induces the hepatic cytochrome P450 ...metabolic enzymes less than the carbamazepine does. However, limited data exist for the influence of oxcarbazepine on thyroid function in children and adolescents. The objective of this study was to determine the effect of oxcarbazepine on thyroid function in these patients.
Methods
A total of 162 pediatric patients with epilepsy who started oxcarbazepine for the first time between April 2003 and May 2020 were enrolled. The longitudinal effects of oxcarbazepine for thyroid functions were confirmed using general estimating equations.
Results
Serum triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4) levels decreased significantly during 5 years of follow‐up (all p’s < .001). In particular, T3 and fT4 levels were reduced steeply in the first 2 years of oxcarbazepine treatment. There was no significant change in thyroid‐stimulating hormone during oxcarbazepine treatment.
Significance
Serum T3, T4, and fT4 levels decreased significantly during oxcarbazepine use, and this change was maintained during the treatment period. In patients receiving oxcarbazepine, it is recommended that periodic thyroid function testing should be performed, especially within the first 2 years after starting this ASM. Our results indicate that oxcarbazepine‐induced hypothyroidism does not appear to be accompanied by a significant increase in TSH, and consequently might be missed if TSH alone is monitored as a measure of thyroid dysfunction.
Introduction
The optimal analgesic modality for patients undergoing hepato-pancreato-biliary (HPB) surgery remains unknown. The analgesic effects of a multimodal intrathecal analgesia (MITA) ...technique of intrathecal morphine (ITM) in combination with clonidine and bupivacaine compared to ITM alone have not been investigated in these patients.
Methods
We performed a multicenter retrospective study of patients undergoing complex HPB surgery who received ITM, bupivacaine, and clonidine (MITA group) or ITM-only (ITM group) as part of their perioperative analgesia strategy. The primary outcome was the unadjusted oral morphine equivalent daily dose (oMEDD) in milligrams on postoperative day 1. After adjusting for age, body mass index, hospital allocation, type of surgery, operation length, and intraoperative opioid use, postoperative oMEDD use was investigated using a bootstrapped quantile regression model. Other prespecified outcomes included postoperative pain scores, opioid-related adverse events, major complications, and length of hospital stay.
Results
In total, 118 patients received MITA and 155 patients received ITM-only. The median (IQR) cumulative oMEDD use on postoperative day 1 was 20.5 mg (8.6:31.0) in the MITA group and 52.1 mg (18.0:107.0) in the ITM group (P < 0.001). There was a variation in the magnitude of the difference in oMEDD use between the groups for different quartiles. For the MITA group, on postoperative day 1, patients in the 25
th
percentile required 14.0 mg less oMEDD (95% CI: -25.9 to -2.2; P = 0.025), patients in the 50
th
percentile required 27.8 mg less oMEDD (95% CI: -49.7 to -6.0; P = 0.005), and patients in the 75
th
percentile required 38.7 mg less oMEDD (95% CI: -72.2 to -5.1; P = 0.041) compared to patients in the same percentile of the ITM group. Patients in the MITA group had significantly lower pain scores in the postoperative recovery unit and on postoperative days 1 to 3. The incidence of postoperative respiratory depression was low (<1.5%) and similar between groups. Patients in the MITA group had a significantly higher incidence of postoperative hypotension requiring vasopressor support. However, no significant differences were observed in major postoperative complications, or the length of hospital stay.
Conclusion
In patients undergoing complex HPB surgery, the use of MITA, consisting of ITM in combination with intrathecal clonidine and bupivacaine, was associated with reduced postoperative opioid use and resulted in superior postoperative analgesia without risk of respiratory depression when compared to patients who received ITM alone. A randomized prospective clinical trial investigating these two intrathecal analgesic techniques is justified.
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