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BackgroundWhether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied.MethodsA total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index (Ctdindex).ResultsGiven the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yieldedCtdindex of 0.7236–0.8222 and 0.7279–0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the bestCtdindex of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level.ConclusionsDeep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.

The exposure levels of disease-causing bacteria and germs were assessed on aircraft cleaning workers on multiple different aircrafts.Five measuring points were selected depending on the aircraft types. Four aircraft cleaning agencies were selected for the test. Aircraft cleaning work was classified as intensive cleaning and general cleaning work. Ventilation in aircraft when sampling during the cleaning operation was categorized into forced ventilation and natural ventilation. The collection of airborne microorganisms was made through inertial impactors which were installed 1.5 meters above the bottom of the aircraft. The airborne bacteria and fungus growth badges were selected by Trytpic Soy Agar and Sabouraud Dextrose Agar.The average concentrations of bacteria in the air were higher in the order of small, medium, and large airplanes. Rainy days had higher concentrations inside and outside the aircraft as compared to those in sunny days. Regarding ventilation, concentrations in natural ventilation were higher than concentrations in forced ventilation. According to the type of work, the concentrations in the intensive cleaning groups (cleaning one plane a day) were lower than those of the ordinary cleaning groups (cleaning several planes per day).The concentration levels of airborne bacteria and fungi in the aircraft surveyed were lower than the indoor environmental standards of Korea (800 cfu/m

Purpose : This study investigated coronavirus disease-19 (COVID-19) related stress, resilience, and organizational commitment, and determined the factors influencing nurses’ organizational commitment at an infectious disease hospital of COVID-19.Methods : A cross-sectional descriptive survey was conducted with 138 nurses. Data analysis, including descriptive statistics, independent t-tests, one-way ANOVA, Pearson’s correlations, and multiple regression analysis, were performed using SPSS 26.0 program.Results : Factors influencing organizational commitment included resilience (β=0.31, pβ=0.31, pβ=-0.26, pβ=-0.19, p=.012). These variables explained 29.6% of the organizational commitment.Conclusion : In order to enhance the organizational commitment of nurses in infectious disease hospitals of COVID-19, active program development and intervention are required at the organizational level to improve nurses’ resilience and relieve stress related to nursing infectious disease patients.

PurposeTo investigate the utility of preoperative multiparametric magnetic resonance imaging (mpMRI)-based clinical-radiomic analysis combined with machine learning (ML) algorithms in predicting the expression of the Ki-67 proliferative index and p53 tumor suppressor protein in patients with meningioma.MethodsThis multicenter retrospective study included 483 and 93 patients from two centers. The Ki-67 index was classified into high (Ki-67≥5%) and low (Ki-67ResultsIn the multivariate analysis, larger tumor volumes (pConclusionThe present study developed clinical-radiomic ML models to non-invasively predict Ki-67 and p53 expression in meningioma using mpMRI features, and provides a novel non-invasive strategy for assessing cell proliferation.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. Anti-inflammatory effects of IVSK was evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of inflammatory mediators, interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) and the mRNA expression of IL-6, IL-8, MCP-1 and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, and nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

Determination of the formation of bright molecular fluorphores during the synthesis of pyrene-derived CNDs, through extensive separation and systematic characterization.

In recent years, it has been observed that when a fire occurs in a multi-use facility, a toxic fire smoke rapidly rises through the vertical shaft and spreads due to the chimney effect and hot buoyancy. Generally, the fire smoke spreads rapidly through a number of evacuation passages installed for safe evacuation, which adversely affects an emergency situation. Due to the lack of this knowledge among the occupants, the majority of the occupants are evacuated using the stairwells, getting suffocated by poisonous smoke and suffering serious injuries. The present study considered the fire smoke spreading vertically through the stairwell. For this purpose, the power of the heat source and the area of the ventilation windows connected to the stairwell were modified, and the movement and diffusion of the hot plume rising vertically in the stairwell were observed. For the experiment, a 1/20 scaled-down stairwell model was employed, and the temperature ‘T’ and the vertical velocity ‘w’ of the hot plume rising inside the stairwell were measured using a 60 W-180 W heat source power. Numerical analysis was performed using FDS under similar conditions, and the results were compared with the experimental results.

더덕(Codonopsis lanceolata)은 주로 한국, 중국 등 동아시아 지역에 재배되고 있으며, 더덕의 뿌리는 기침, 기관지염, 천식, 결핵, 소화 불량의 증상을 치료하기 위한 기능성 식품 및 전통 의학으로 사용되어져 왔다. 보고된 바에 의하면 phenylpropanoids, polyacetylenes, saponins, flavonoids와 같은 다양한 식물 천연물 성분들이 항비만, 항염, 항암, 항산화, 항미생물 활성과 같은 약리학적 작용에 관여한다고 보고되어 있다. MS기반 대사체학 분석을 이용한 주산지의 마커 성분을 선정하는 것은 다른 지역에서 재배된 약용 식물의 안전성뿐만 아니라 화학적 조성과 생물학적 효능의 변화와도 관련이 있기 때문에 부작용 없이 더덕의 유익한 효과만을 보장하는데 중요하다. 본 연구에서는 국내산 더덕의 주산지 특성을 구별하기 위해 UPLC-QTOF-MS를 기반으로 하는 대사체 프로파일링과 다변량 통계분석 기법인 PCA 분석을 수행하여 판별모델을 확립하였다. 그 결과 인제(강원도), 횡성(강원도), 무주(전라북도)의 3개 그룹이 PCA와 loading plot 분석결과 tangshenoside I, lancemaside A, lancemaside G는 더덕 주산지를 구별하기 위한 잠재적 대사체 마커들로 제안하였다.

올리브 (Olea europaea L.) 잎은 풍부한 폴리 페놀을 함유하고 있으며, 이는 항산화, 항균, 항 바이러스, 항암 활성을 연관시키고 혈소판 활성화를 억제하는 것으로 보고 되어있다. 올리브 잎은 건강기능성식품 및 기능성 화장품의 원료로 상업적으로 사용되고 있으며, 이러한 건강상의 이점은 올리브 잎의 주요 생리활성 물질인 oleuropein와 관련이 있다. Oleuropein은 항산화, 항노화, 항염증, 항암, 항미생물, 항바이러스, 항죽상동맥혈증, 지질 저하 효과, 혈당 저하 효과, 피부 보호 효과가 보고되어 있다. oleuropein이 올리브 잎의 중요한 화합물 임에도 불구하고 상업용 제품에서 oleuropein 함량을 밝히는 정량적 접근 방법은 아직 없다. 본 연구에서는 UPLC-QTof/MS, PDA, CAD로 개발된 방법을 이용하여 10개의 상업용 올리브 잎 추출물의 성분 및 oleuropein 함량을 분석 하였다. Iridoids (1, 3, 4, 14, and 16-18), coumarin (2), phenylethanoids (5, 9, and 11), flavonoids (6-8, 10, 12, and 13), lignan (15)을 포함한 총 18종의 화합물이 올리브 잎에서 예상되었다. 총 10종의 올리브 잎 추출물 분석은 3종의 제품(A, G, H)에서 제품에서 제시한 oleuropein 함량보다 높게, 5종의 제품(B, E, H, I, J)에서 5-10%의 오차범위로 나타났고 C, D에서 함량 미달로 검출되었다. 본 연구에서 oleuropein의 함량분석이 올리브 잎의 품질 관리에 도움이 될 수 있음을 판단하였다.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1–3, isoflavonoid derivatives 4–11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1–13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.

Objective Extremely low alanine transaminase (ALT) levels are associated with all-cause mortality in frail elderly individuals; the clinical significance of ALT as a reliable biomarker is now being considered. Predicting mortality with routine tests at the time of diagnosis is important for managing patients after intracranial hemorrhage. We aimed to investigate whether an extremely low ALT level is associated with mortality in the elderly after intracranial hemorrhage. Methods A retrospective review was performed on 455 patients with intracranial hemorrhage admitted to a university-affiliated tertiary care hospital from February 2014 to May 2019. Multivariate Cox regression analysis was performed for all ages and for each age group to determine whether an extremely low ALT level is an independent predictor of mortality only in the elderly. Results Overall, 294 patients were enrolled, and the mean age of the subjects was 59.1 years, with 99 (33.8%) aged ≥65 years. The variables associated with all-cause mortality in all subjects were age, C-reactive protein (CRP) levels, hemoglobin (Hb) levels (

The aim of this study was to jointly model COVID-19 test positivity rates and hospitalizations in Texas using Bayesian joinpoint regression. The data for both test positivity rates and hospitalizations were obtained from the Texas Department of State Health Services between April 5 and October 19, 2020. The stage 1 model identifies four significant shifts in test positivity rates, three of which occur roughly 9 days after documented policy or behavioral changes statewide. Estimated positivity rates from the first model were then used to predict hospitalization rates and to estimate lag time between changes in positivity and hospitalization. The resulting lag time is 9.056 days (± 3.808). Both models are valuable to policy makers and public health officials as they study the impact of behavioral patterns on disease prevalence and resulting hospitalizations. © 2021 - IOS Press. All rights reserved.

The capability of quantum dots to generate both single and multiexcitons can be harnessed for a wide variety of applications, including those that require high optical gain. Here, we use time-correlated photoluminescence (PL) spectroscopy to demonstrate that the isolation of single CdSeTe/ZnS core-shell, nanocrystal quantum dots (QDs) in Zero Mode Waveguides (ZMWs) leads to a significant modification in PL intensity, blinking dynamics, and biexciton behavior. QDs in aluminum ZMWs (AlZMWs) exhibited a 15-fold increase in biexciton emission, indicating a preferential enhancement of the biexciton radiative decay rate as compared to the single exciton rate. The increase in biexciton behavior was accompanied by a decrease in blinking events due to a shortening in the dark state residence time. These results indicate that plasmon mediated enhanced decay rates of QDs in AlZMWs lead to substantial changes in the photophysical properties of single quantum dots, including an increase in biexciton behavior.

This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis to identify potent bacterial neuraminidase (bNA) inhibitors from the Broussonetia papyrifera roots extract. To isolate unbound compounds from the enzyme-binding complex, the root bark extracts were either incubated in the absence of bNA, in the presence of bNA, or with the time-dependent bNA before the ultrafiltration was performed. Thirteen flavonoids were separated from the target extract, and their inhibitory activities were tested against bNA. The isolated flavonoids exhibited potent inhibition against NA (IC50 = 0.7–54.0 μM). Our kinetic analysis of representative active flavonoids (1, 2, and 6) showed slow and time-dependent reversible inhibition. Additionally, chalcones exhibited noncompetitive inhibition characteristics, whereas flavonols and flavans showed mixed-type behavior. The computational results supported the experimental behaviors of flavonoids 2, 6, 10, and 12, indicating that bounded to the active site, but flavonoids 6 and 10 binds near but not accurately at the active site. Although this is mixed-type inhibition, their binding can be considered competitive.

Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have been attracted as candidate treatments for Alzheimer's disease (AD). Fifteen khellactone-type coumarins from the roots of Peucedanum japonicum Thunberg were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and MAO inhibitory activities. Compound 3′-angeloyl-4′-(2-methylbutyryl)khellactone (PJ13) most potently inhibited AChE (IC50 = 9.28 µM), followed by 3′-isovaleryl-4′-(2-methylbutyroyl)khellactone (PJ15) (IC50 = 10.0 μM). Compound senecioyl-4′-angeloyl-khellactone (PJ5) most potently inhibited BChE (IC50 = 7.22 μM) and had the highest selectivity index (> 5.54), followed by 3′-senecioyl-4′-(2-methylbutyryl)khellactone (PJ10) and 3′,4′-disenecioylkhellactone (PJ4) (IC50 = 10.2 and 10.7 μM, respectively). Compounds PJ13, PJ15, and PJ5 showed reversible and mixed-types of inhibition with Ki values of 5.98, 10.4 (for AChE), and 4.16 µM (for BChE), respectively. However, all 15 compounds weakly inhibited MAO-A and MAO-B. Molecular docking simulation revealed that PJ13 had a higher binding affinity (− 9.3 kcal/mol) with AChE than PJ15 (− 7.8 kcal/mol) or PJ5 (− 5.4 kcal/mol), due to the formation of a hydrogen bond with Tyr121 (distance: 2.52 Å). On the other hand, the binding affinity of PJ5 (− 10.0 kcal/mol) with BChE was higher than for PJ13 (− 7.7 kcal/mol) or PJ15 (− 8.1 kcal/mol), due to the formation of a hydrogen bond with Ser198 (distance: 2.05 Å). These results suggest that PJ13 and PJ5 are potential reversible selective inhibitors of AChE and BChE, respectively, for the treatment of AD.

Agastache rugosa (fisch.C.A. Mey.) Kuntze (A. rugosa) is used in traditional medicine in Korea since it has variety of medicinal activities, such as antioxidant, anti-inflammatory, anti-photoaging. Acacetin, tilianin, and rosmarinic acid are the active components of A. rugosa but their metabolites have not yet been fully identified. The purpose of this study was to identify the metabolites of A. rugosa after oral administration in Sprague-Dawley rats. For this study, active components (acacetin, tilianin, rosmarinic acid) and A. rugosa extract were dissolved in 0.5% carboxymethyl cellulose sodium solution respectively and treated by oral gavage at a dose of 50 mg/kg (for single compounds) and 200 mg/kg (for A. rugosa extract). For metabolite identification, plasma, urine, and fecal samples were collected after oral administration and analyzed using liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) for data acquisition and metabolite identification. Metabolite identification was performed by considering the mass difference of the metabolites from the parent compounds and using their exact m/z and MS/MS fragments. The main biotransformation of the major components of A. rugosa was hydrolysis to acacetin, followed by demethylation, methylation, and conjugation. That of rosmarinic acid is methylated and conjugated. There were differences in metabolism between the treatment of single active components and extract; some sulfate-conjugated metabolites or metabolic intermediates were only detected in the treatment of single active components. The reason for this is thought to be the low content of the active components in the extract, which react competitively with the components present in the extract in the metabolic process. This study provides valuable evidence for a comprehensive understanding of the metabolism of A. rugosa.

Upconverting nanoparticles (UCNPs) composed of NaYF

As a highly abundant renewable carbon source, lignin can be converted to a variety of advanced carbon materials with tailorable properties through slow pyrolysis. In this study, slow pyrolysis of kraft lignin, for the first time, was investigated with a commercial pyrolysis–gas chromatography−mass spectrometry (Py-GC-MS) system through evolved gas analysis-MS (EGA-MS) and heart-cutting-GC-MS (HC-GC-MS) analyses. These analyses allow recovery and examination of the multi-phased gas products generated from thermal decomposition of lignin during slow pyrolysis over long time course thus making it possible to link pyrolysis chemistry and carbon material properties. The overall product distributions, including volatiles and solid product were quantitatively tracked at different heating rates (2, 20, 40 ℃/min) and different temperature regions (100-200, 200-300 and 300-600 ℃). Solid residues were further characterized using a suite of analytical tools, in correlation with the investigation of formation mechanisms of volatiles to reveal the reaction chemistry of lignin during slow pyrolysis, and to determine the morphology, pore structure, and interfacial chemical properties. This study provides critical insights into the slow pyrolysis chemistry of lignin and the properties of the resulting carbon material. These results will facilitate a better design and control of the lignin slow pyrolysis process for synthesizing functional carbon materials.

Ruthenium(II) complexes developed for photodynamic therapy (PDT) are almost exclusively tris-bidentate systems with C2 or D3 symmetry. This is due to the fact that this structural framework commonly produces long-lived excited states, which, in turn, allow for the generation of large amounts of singlet oxygen (1O2) and other reactive oxygen species. Complexes containing tridentate ligands would be advantageous for biological applications as they are generally achiral (D2d or C2v symmetry), which eliminates the possibility of multiple isomers which could exhibit potentially different interactions with chiral biological entities. However, Ru(II) complexes containing tridentate ligands are rarely studied as candidates for photobiological applications, such as PDT, since they almost exclusively exhibit low quantum yields and very short excited-state lifetimes and, thus, are not capable of generating sufficient 1O2 or engaging in electron transfer reactions. Here, we report a proof-of-concept approach to make bis-tridentate Ru(II) complexes useful for PDT applications by altering their photophysical properties through the inclusion of N-heterocyclic carbene (NHC) ligands. Three NHC and two terpyridine ligands were studied to evaluate the effects of structural and photophysical modulations of bis-substituted Ru(II) complexes. The NHC complexes were found to have superior excited-state lifetimes, 1O2 production, and photocytotoxicity. To the best of our knowledge, these complexes are the most potent light-activated bis-tridentate complexes reported.

The vulnerabilities of high-rise buildings to fires and the safe evacuation of the occupants therein have been consistently highlighted in the media. Unexpected natural disasters that occur frequently such as earthquakes increase the potential risk in large cities. If an earthquake with a magnitude that exceeds the load for safety design occurs and causes a fire in a high-rise building, it would lead to serious casualties among the occupants evacuating the building. This study represented the stairs in high-rise buildings using several full-scale models and examined the characteristics of a high temperature plume rising vertically from the ignition source using numerical analysis with Fire Dynamics Simulator (FDS). We analyzed the effects of calorific value and ventilation in the middle floors and examined the time taken by a plume rising vertically from the stairs to reach each floor. Furthermore, the empirical line suggested by McCaffrey (1979) was used to compare the characteristics of a plume rising vertically inside stairs and in a limited space with those of a plume rising vertically in an open space. Based on the time taken by a plume front to rise, which is calculated based on numerical analyses, this study identified and suggested an experiment equation to make it possible to predict the time taken by a plume to rise from the stairs in a typical high-rise building.