Two cheap, simple and reproducible methods for the electrophoretic determination of homocysteine thiolactone (HTL) in human urine have been developed and validated. The first method utilizes off-line single drop microextraction (SDME), whereas the second one uses off-line SDME in combination with field amplified sample injection (FASI). The off-line SDME protocol consists of the following steps: urine dilution with 0.2 mol/L, pH 8.2 phosphate buffer (1:2, v/v), chloroform addition, drop formation and extraction of HTL. The pre-concentration of HTL inside a separation capillary was performed by FASI. For sample separation, the 0.1 mol/L pH 4.75 phosphate buffer served as the background electrolyte, and HTL was detected at 240 nm. A standard fused-silica capillary (effective length 55.5 cm, 75 μm id) and a separation voltage of 21 kV (~99 μA) were used. Electrophoretic separation was completed within 7 min, whereas the LOD and LOQ for HTL were 0.04 and 0.1 μmol/L urine, respectively. The calibration curve in urine was linear in the range of 0.1–0.5 μmol/L, with R² = 0.9991. The relative standard deviation of the points of the calibration curve varied from 2.4% to 14.9%. The intra- and inter-day precision and recovery were 6.4–10.2% (average 6.0% and 6.7%) and 94.9–102.7% (average 99.7% and 99.5%), respectively. The analytical procedure was successfully applied to the analysis of spiked urine samples obtained from apparently healthy volunteers. Full article

A plasma photonic crystal (PPC) was formed using an array of discharge plasma tubes. The transmission spectra and bandstructure of PPCs with different lattice types under different polarization modes were studied through simulation and measurement. To study the types of bandgap in PPCs, the bandstructure of the PPC is calculated using symplectic finite difference time domain (SFDTD), a modified plane wave expansion (PWE) method, and a finite element method (FEM) based on weak form equations. The bandstructure of the PPC is compared with the transmission curve results. The results show that the bandgap is stable in the PPC, and the experimental and numerical results of the transmission spectra agree well. There are different types of bandgap in the PPC; the bandgap under TE-like polarization is caused by localized surface plasmon (LSP) and Bragg scattering. The bandgap under TM-like polarization is caused by the cutoff effect of plasma on the electromagnetic wave and Bragg scattering. The lattice type also affects the position and number of the bandgap. The three methods have their advantages and disadvantages when calculating bandstructure. Therefore, it is necessary to combine the results of three methods and experimental results to accurately determine the bandgap type of the PPC. Full article

Chips are obtained by subtractive processes such as machining workpieces and until recently considered as waste. However, in recent years they are shown to have great potential as sustainable raw materials for powder technologies. Powder production from metal chips, through the application of solid-state processes, seems to be an alternative to conventional atomization from liquid cooled with different fluids. However, chip material and processing have an essential role in the characteristics of powder particles, such as particle size, shape, size distribution and structure (4S’s), which are essential parameters that must be considered having in mind the powder process and the metallurgy applications. Moreover, different approaches refereed in the application of this new “powder process” are highlighted. The goal is to show how the actual research has been transforming subtractive processes from a contributor of wastes to clean technologies. Full article

c-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects. Eight compounds exhibited submicromolar binding affinity for at least one JNK isoform. Most of these compounds also inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) activation and interleukin-6 (IL-6) production in human monocytic THP1-Blue cells and human MonoMac-6 cells, respectively. Selected compounds (4f and 4m) also inhibited LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. We conclude that indenoquinoxaline-based oximes can serve as specific small-molecule modulators for mechanistic studies of JNKs, as well as potential leads for the development of anti-inflammatory drugs. Full article

In this study, proximal composition, mineral analysis, polyphenolic compounds identification, and antioxidant and functional activities were determined in green bean (GBF), mesquite (MF), and pea (PF) flours. Different mixtures of legume flour and wheat flour for bread elaboration were determined by a simplex-centroid design. After that, the proximal composition, color, specific volume, polyphenol content, antioxidant activities, and functional properties of the different breads were evaluated. While GBF and PF have a higher protein content (41–47%), MF has a significant fiber content (19.9%) as well as a higher polyphenol content (474.77 mg GAE/g) and antioxidant capacities. It was possible to identify Ca, K, and Mg and caffeic and enolic acids in the flours. The legume–wheat mixtures affected the fiber, protein content, and the physical properties of bread. Bread with MF contained more fiber; meanwhile, PF and GBF benefit the protein content. With MF, the specific bread volume only decreased by 7%. These legume flours have the potential to increase the nutritional value of bakery goods. Full article

A lithium titanate oxide (LTO) anode based battery has high power density, and it is widely applied in transportation and energy storage systems. However, the thermal performance of LTO anode based battery module is seldom studied. In this work, a heat generation theoretical model of the battery is explored. The thermal performance of LTO anode based battery modules under high discharge rates is studied by both experiment and simulation. It is found that the temperature rise of the battery can be estimated accurately with the calculation of the equivalent internal resistance under different discharge rates. In addition, under the same depth of discharge, both the temperature rise and the temperature difference in the battery module increase with the discharge rates. Full article

Exposure to air pollutants in wildfire smoke and indoor pollution causes lung diseases. Short-term exposure to wood smoke (WS) is partially known to alter the expression of human matrix metalloproteinases (MMPs), inflammatory cytokines, and tissue inhibitors of metalloproteinases (TIMPs). Accordingly, we investigated the effect of exposing guinea pigs to WS for two and four three-hour periods on different days. The daily content of particles reported by indoor pollution was produced by 60 g of pinewood. We analyzed the cell profile and collagen content in bronchoalveolar lavages (BAL). The mRNA expression of pro-inflammatory cytokines, MMPs, and TIMPs was studied in lung tissue. Cytokines and gelatinolytic activity were analyzed in BAL and serum. The results showed that total cells, macrophages, neutrophils, and collagen increased in BAL, whereas neutrophils and lymphocytes decreased. TGF-β1, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MMP-2, MMP-9, TIMP-1, and TIMP-2 were upregulated in lungs, downregulating IL-12. TNF-α, IFN-γ, TGF-β1, IL-1β, IL-6, and IL-8 were increased in BAL and serum, decreasing IL-12. Gelatinase activity was increased in serum. Thus, guinea pigs exposed to short-term domestic doses of WS overexpressed pro-inflammatory cytokines, MMPs, and TIMPs. These results are similar to ECM remodeling and pulmonary and systemic inflammation reported in humans. Full article

Oral minoxidil is an approved treatment for high blood pressure which is also used as an off-label drug for alopecia. Knowledge about the effects of systemic minoxidil in the paediatric population is limited. A retrospective case series study of paediatric patients with history of systemic minoxidil intake due to contaminated sets of omeprazole was performed to describe side effects of high dose oral minoxidil intake in children. Twenty patients aged between 2 months and 13 years joined the study. They had received high doses of oral minoxidil (mean dose 0.90 mg/kg/day) during a mean time of 38.3 days. Hypertrichosis appeared in 65%, with a mean latency time of 24.31 days. Treatment time was associated with the appearance of hypertrichosis (p < 0.05). Most common initial zone of hypertrichosis was the face. Systemic effects developed in 15%, with no cases of severe disorders. The present study shows a novel insight into the side effects of high doses of oral minoxidil in children. Full article

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R² = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring. Full article

Introduction: Adherence to medications is very crucial for an optimized clinical outcome in the management of chronic diseases. Beliefs about medications and other factors can significantly affect adherence to chronic medications. The objective of the present research was to identify the associated factors of adherence to medication in Jordanian patients with chronic diseases utilizing a stepwise binary logistical regression model. Methods: A cross-sectional study was carried out between November 2018 and March 2020. The participants were reached from secondary and tertiary care setting clinics in Jordan. The recruited patients were asked to report their attitudes of adherence to medications and beliefs about medications via filling out the MARS-5 and BMQ-specific tools. Sociodemographic data were also collected from the recruited patients and included in the regression model. A stepwise binary logistical regression model was applied to identify the associated factors of adherence to chronic medications in the tested sample. Results: A total of 485 patients who met the inclusion criteria were recruited. The mean age of the participants was 57.14 (age ranged from 22 to 82 years). Around 39% of the participants were older than 65 years. Most of the patients were either hypertensive or diabetic (35.7% and 32.2%, respectively). The logistic regression model indicated that necessity beliefs are strongly associated with adherence (OR 4.22), while concerns beliefs, dosage frequency and having medical insurance were negatively associated with adherence (OR 0.73, 0.74 and 0.26, respectively), with a p-value ≤ 0.05. Conclusions: Both the MARS-5 and BMQ-specific questionnaires were applied successfully on the tested sample. Better attention should be paid to the logistic regression model variables that were associated with adherence in order to guarantee optimal treatment outcomes in the treatment of chronic diseases. Full article

Objective: Signet-ring cell carcinoma (SRCC) is a rare histopathological subtype of colorectal cancer (CRC) constituting approximately 1% of CRC cases. This study analyzed the incidence and survival rates of colorectal SRCC. Methods: We analyzed the incidence and survival rates of colorectal SRCCs based on patients’ data of the Korea Central Cancer Registry. Results: The age-standardized incidence rates of colon and rectum SRCC in 2017 were 0.17 and 0.07 individuals per 100,000, respectively. Between 1993 and 2017, the 1-, 2-, 3-, 4-, and 5-year relative survival rates of patients with colon SRCC were 65.6%, 49.0%, 38.9%, 34.9%, and 33.0%, respectively, while those of patients with rectum SRCC were 69.6%, 47.8%, 38.5%, 32.8%, and 29.4%, respectively. According to the Surveillance, Epidemiology, and End Results summary stages, the 5-year relative survival rates of colon SRCC between 1993 and 2017 were 70.4% for the localized stage, 41.0% for the regional stage, and 7.0% for the distant stage, while those for rectum SRCC were 60.7%, 34.4, and 3.3%, respectively. Conclusions: Although the incidence of colorectal SRCC is extremely low in South Korea, it has been increasing in recent decades. As the prognosis of colorectal SRCC is extremely poor; clinicians should be aware of the differential diagnosis of SRCC in colorectal cancer cases. Full article

Inhibition of K⁺-conductance through the human ether-a-go-go related gene (hERG) channel leads to QT prolongation and is associated with cardiac arrhythmias. We previously reported that physiological concentrations of some estrogens partially suppress the hERG channel currents by interacting with the S6 residue F656 and increase the sensitivity of hERG blockade by E-4031. Although these studies suggested that clinically used synthetic estrogens with similar structures have the marked potential to alter hERG functions, the hERG interactions with synthetic estrogens have not been assessed. We therefore examined whether ethinylestradiol (EE2), a synthetic estrogen used in oral contraceptives, affects hERG function and blockade by drugs. Supratherapeutic concentrations of EE2 did not alter amplitudes or kinetics of the hERG currents elicited by train pulses at 20 mV (0.1 Hz). On the other hand, EE2 at therapeutic concentrations reduced the degree of hERG current suppression by E-4031. The administration of EE2 followed by E-4031 blockade reversed the current suppression, suggesting that the interaction of EE2 and E-4031 alters hERG at the drug-binding site. The effects of EE2 on hERG blockade raised the possibility that other estrogens, including synthetic estrogens, can alter hERG blockade by drugs that cause QT prolongation and ventricular arrhythmias. Full article

Clear-sky detection (CSD) is of critical importance in solar energy applications and surface radiative budget studies. Existing CSD methods are not sufficiently validated due to the lack of high-temporal resolution and long-term CSD ground observations, especially at polluted sites. Using five-year high resolution ground-based solar radiation data and visual inspected Total Sky Imager (TSI) measurements at polluted Xianghe, a suburban site, this study validated 17 existing CSD methods and developed a new CSD model based on a machine-learning algorithm (Random Forest: RF). The propagation of systematic errors from input data to the calculated global horizontal irradiance (GHI) is confirmed with Mean Absolute Error (MAE) increased by 99.7% (from 20.00 to 39.93 W·m⁻²). Through qualitative evaluation, the novel Bright-Sun method outperforms the other traditional CSD methods at Xianghe site, with high accuracy score 0.73 and 0.92 under clear and cloudy conditions, respectively. The RF CSD model developed by one-year irradiance and TSI data shows more robust performance, with clear/cloudy-sky accuracy score of 0.78/0.88. Overall, the Bright-Sun and RF CSD models perform satisfactorily at heavy polluted sites. Further analysis shows the RF CSD model built with only GHI-related parameters can still achieve a mean accuracy score of 0.81, which indicates RF CSD models have the potential in dealing with sites only providing GHI observations. Full article

Anthracnose disease caused by Colletotrichum spp. makes heavy losses for post-harvest mangoes of Cat Hoa Loc variety during storage, packaging, and transportation. The synthetic fungicides are commonly used to control the disease, but they are not safe for consumers’ health and environment. This study was aimed to investigate the use of essential oils (EOs) as the safe alternative control. Pathogen was isolated from the infected Cat Hoa Loc mangoes and identified by morphology and DNA sequencing of the ITS region. Six EOs (cinnamon, basil, lemongrass, peppermint, coriander, and orange) were chemically analyzed by GC–MS. The antifungal activity of EOs was studied in vitro and in vivo. The results showed that the isolated pathogen was Colletotrichum acutatum. Cinnamon, basil, and lemongrass EOs effectively inhibited the growth of C. acutatum in descending order of cinnamon, basil, and lemongrass. However, they (except basil oil) severely damaged fruit peels. The antifungal activity was closely related to the main compounds of EOs. Basil EOs effectively controlled anthracnose development on Cat Hoa Loc mangoes artificially infected with C. acutatum, and its effectiveness was comparable to that of fungicide treatment. Consequently, basil EOs can be used as a biocide to control anthracnose on post-harvest Cat Hoa Loc mangoes. Full article

Delays in the execution stage of road construction projects are one of the significant challenges. The incapability of finishing projects according to schedule has attracted many researchers’ attention to this issue. This study has been formed to investigate delays in road construction projects from a risk management perspective. In this study, risks have been identified by structured interviews with experts. Qualitative risk analysis by a survey of experts and quantitative risk analysis by analytical hierarchy process (AHP) technique have been performed. Research results show that financial and credit problems, lands’ funding, management problems, technical problems, and natural disasters have the highest risk among the main criteria. Among the subcriteria of the risk, incomplete funding with a weight of 0.188, gardens and land price with 0.114 are the most critical risk, and ground operations with 0.017, asphalt problems with 0.009, and accident insurance with a weight of 0.006 are the least essential risk. In the following, critical criteria analysis has been performed, and solutions to reduce or eliminate these delays in road construction projects are presented. Full article

The purpose of this study was to investigate the prevalence of self-reported restrictive eating, current or past eating disorder, and menstrual dysfunction and their relationships with injuries. Furthermore, we aimed to compare these prevalences and associations between younger (aged 15–24) and older (aged 25–45) athletes, between elite and non-elite athletes, and between athletes competing in lean and non-lean sports. Data were collected using a web-based questionnaire. Participants were 846 female athletes representing 67 different sports. Results showed that 25%, 18%, and 32% of the athletes reported restrictive eating, eating disorders, and menstrual dysfunction, respectively. Higher rates of lean sport athletes compared with non-lean sport athletes reported these symptoms, while no differences were found between elite and non-elite athletes. Younger athletes reported higher rates of menstrual dysfunction and lower lifetime prevalence of eating disorders. Both restrictive eating (OR 1.41, 95% CI 1.02–1.94) and eating disorders (OR 1.89, 95% CI 1.31–2.73) were associated with injuries, while menstrual dysfunction was associated with more missed participation days compared with a regular menstrual cycle (OR 1.79, 95% CI 1.05–3.07). Our findings indicate that eating disorder symptoms and menstrual dysfunction are common problems in athletes that should be managed properly as they are linked to injuries and missed training/competition days. Full article

The description of Medical Student Syndrome is based on the assumption that inexperienced medical students are prone to develop a pathological fear of medical conditions they are taught about. The aim of this study is to examine the sample of students (medical and non-medical) in order to assess and compare their level of hypochondriacal attitudes and health-related anxiety. We also examined other factors which might have had an influence on hypochondria and nosophobia attitudes among students. Methods: The study was conducted in two groups of students: 313 medical students at the Medical University of Silesia and 293 students at non-medical universities in Katowice, Poland. The study used the medical student syndrome self-explanatory questionnaire constructed for the study, taking into account the specificity of the group and the research problem. The research questionnaire was completed in an online survey by 606 students. Results: The results of the study showed that medical students obtained the same scores on a nosophobic scale as the non-medical students (p = 0.5). The analysis of hypochondriacal behavior showed significantly higher results in the non-medical student group (p = 0.02). In the entire study group, females and participants with mental disorders obtained higher scores in relation to nosophobia. Symptoms of depression and anxiety were more common in the group of medical students. Conclusions: Medical studies are not a risk factor for the occurrence of health anxiety and hypochondrial attitudes. Such factors are female gender and having a mental illness. Full article

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 has been noted. We exposed human HEK293 and mouse As4.1 renal cells to experimental IH or normoxia for 24 h and then measured the mRNA levels using a real-time reverse transcription polymerase chain reaction. The mRNA levels of Renin (Ren) and Cd38 were significantly increased by IH, indicating that they could be involved in the CD38-cyclic ADP-ribose signaling pathway. We next investigated the promotor activities of both genes, which were not increased by IH. Yet, a target mRNA search of the microRNA (miRNA) revealed both mRNAs to have a potential target sequence for miR-203. The miR-203 level of the IH-treated cells was significantly decreased when compared with the normoxia-treated cells. The IH-induced upregulation of the genes was abolished by the introduction of the miR-203 mimic, but not the miR-203 mimic NC negative control. These results indicate that IH stress downregulates the miR-203 in renin-producing cells, thereby resulting in increased mRNA levels of Ren and Cd38, which leads to hypertension. Full article

Flexible PVC/BT (Polyvinyl chloride/Barium Titanate) composite thick films with (0–30%) volume fractions of BaTiO₃ were fabricated via the solution casting method. The effects of BaTiO₃ filler on the phase, microstructure and dielectric properties of composite films were investigated. The XRD results revealed that BT particles are embedded in the PVC matrix with no chemical reaction taking place between the two phases. It was observed that the glass transition temperature of PVC had increased with the addition of BT. The frequency dispersion in the dielectric constant versus temperature curves indicated the relaxor nature of the composites. The dielectric constant (ε_r) measured at 40 °C, increased from 7.6 for pure PVC to 16.1 for 30% of BaTiO₃ content in PVC polymer matrix. It is suggested that BaTiO₃ ceramic powder enhanced the dielectric properties of PVC and may be used as a flexible dielectric material. Full article

Chiral total syntheses of both enantiomers of the anti-MRSA active plymuthipyranone B and all of the both enantiomers of three unnatural and synthetic analogues were performed. These two pairs of four chiral compounds are composed of the same 3-acyl-5,6-dihydro-2H-pyran-2-one structure. The starting synthetic step utilized a privileged asymmetric Mukaiyama aldol addition using Ti(OiPr)₄/(S)-BINOL or Ti(OiPr)₄/(R)-BINOL catalysis to afford the corresponding (R)- and (S)-δ-hydroxy-β-ketoesters, respectively, with highly enantiomeric excess (> 98%). Conventional lactone formation and successive EDCI-mediated C-acylation produced the desired products, (R)- and (S)-plymuthipyranones B and three (R)- and (S)- synthetic analogues, with an overall yield of 42–56% with a highly enantiomeric excess (95–99%). A bioassay of the anti-MRSA activity against ATCC 43300 and 33591 revealed that (i) the MICs of the synthetic analogues against ATCC 43300 and ATCC 33591 were between 2 and 16 and 4 and 16 μg/mL, respectively, and those of vancomycin (reference) were 1 μg/mL. (ii) The natural (S)-plymuthipyranone B exhibited significantly higher activity than the unnatural (R)-antipode against both AACCs. (iii) The natural (R)-plymuthipyranone B and (R)-undecyl synthetic analogue at the C6 position exhibited the highest activity. The present work is the first investigation of the SAR between chiral R and S forms of this chemical class. Full article

Pharmacological allosteric agonists (calcimimetics) of the extracellular calcium-sensing receptor (CaSR) have substantial gastro-intestinal side effects and induce the expression of inflammatory markers in colon cancer cells. Here, we compared the effects of both CaSR-specific (R enantiomers) and -unspecific (S enantiomers) enantiomers of a calcimimetic (NPS 568) and a calcilytic (allosteric CaSR antagonists; NPS 2143) to prove that these effects are indeed mediated via the CaSR, rather than via off-target effects, e.g., on β-adrenoceptors or calcium channels, of these drugs. The unspecific S enantiomer of NPS 2143 and NPS S-2143 was prepared using synthetic chemistry and characterized using crystallography. NPS S-2143 was then tested in HEK-293 cells stably transfected with the human CaSR (HEK-CaSR), where it did not inhibit CaSR-mediated intracellular Ca²⁺ signals, as expected. HT29 colon cancer cells transfected with the CaSR were treated with both enantiomers of NPS 568 and NPS 2143 alone or in combination, and the expression of CaSR and the pro-inflammatory cytokine interleukin 8 (IL-8) was measured by RT-qPCR and ELISA. Only the CaSR-selective enantiomers of the calcimimetic NPS 568 and NPS 2143 were able to modulate CaSR and IL-8 expression. We proved that pro-inflammatory effects in colon cancer cells are indeed mediated through CaSR activation. The non-CaSR selective enantiomer NPS S-2143 will be a valuable tool for investigations in CaSR-mediated processes. Full article

The results of the analysis on some fragments of bronze belts and a bowl discovered from southwestern Armenia at the Yegheghnadzor archaeological site are discussed. The samples are dated to the 7–6th millennium BCE from the Urartian period. The artefacts were corroded, and a multilayer structure was formed. To study the stratigraphy of layers and their composition, the samples have been analyzed using SEM-EDS (Scanning Electron Microscopy, Energy-Dispersive Spectrometry) and OM (Optical Microscopy) techniques. The bronze finds appear with the typical incrustations rich in alloy alteration compounds. Concentrations of copper and tin in the alloys were quantified by SEM-EDS: the pattern and the percentage of the alloy are the same for the belts. Regarding the bowl sample, it is constituted by two foils perfectly in contact but different in color, thickness, and composition. The results evidenced that only two elements participate in forming the alloy composition in the samples: Cu and Sn. The tin content is variable from 7.75% to 13.56%. Other elements such as Ag, As, Fe, Ni, P, Pb, Sb, and Zn make up less than 1% and can be considered as impurities. Full article