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Discoidin domain receptor 1 (DDR1) kinase has emerged as a promising target for cancer therapy, and selective DDR1 inhibitors have shown promise as effective therapeutic candidates. Herein, we have identified the first coumarin-based selective DDR1 inhibitors via repurposing of a recent series of carbonic anhydrase inhibitors. Among these, ureidocoumarins 3a, 3i, and 3q showed the best DDR1 inhibitory activities. The m-trifluoromethoxy phenyl member 3q potently inhibited DDR1 with an IC50 of 191 nM, while it showed less inhibitory activity against DDR2 (IC50 = 5080 nM). 3q also exhibited favorable selectivity in a screening platform with 23 common off-target kinases, including BCR-ABL. In the cellular context, 3q showed moderate antiproliferative effects, while 3i, with the third rank in DDR1 inhibition, exerted the best anticancer activity with sub-micromolar GI50 values over certain DDR1-dependent cell lines. Molecular docking and MD simulations disclosed the putative binding mode of this coumarin chemotype and provided insights for further optimization of this scaffold. The present findings collectively supported the potential improvement of ureidocoumarins 3i and 3q for cancer treatment. [ABSTRACT FROM AUTHOR]

BCR-ABL inhibition is an effective therapeutic approach for the treatment of chronic myeloid leukaemia (CML). Herein, we report the discovery of AKE-72 (5), a diarylamide 3-aminoindazole, as a potent pan-BCR-ABL inhibitor, including the imatinib-resistant mutant T315I. A focussed array of compounds 4a, 4b, and 5 has been designed based on our previously reported indazole I to improve its BCR-ABLT315I inhibitory activity. Replacing the morpholine moiety of I with the privileged tail (4-ethylpiperazin-1-yl)methyl afforded 5 (AKE-72) with IC50 values of < 0.5 nM, and 9 nM against BCR-ABLWT and BCR-ABLT315I, respectively. Moreover, AKE-72 potently inhibited a panel of other clinically important mutants in single-digit nanomolar IC50 values. AKE-72 elicited remarkable anti-leukemic activity against K-562 cell line (GI50 < 10 nM, TGI = 154 nM). In addition, AKE-72 strongly inhibited the proliferation of Ba/F3 cells expressing native BCR-ABL or its T315I mutant. Overall, AKE-72 may serve as a promising candidate for the treatment of CML, including those harbouring T315I mutation. [ABSTRACT FROM AUTHOR]

A series of 6-ureido/amidocoumarins (5a–p and 7a–c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7–82.4 nM) and hCA XII (KIs: 5.9–95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach. Fractionation and characterization of cell-free mRNA carriers - mostly EVs - from various human plasma samples leads to identification of cancer-specific EV enrichment patterns [ABSTRACT FROM AUTHOR]

The emergence of cancer resistance to targeted therapy represents a significant challenge in cancer treatment. Therefore, identifying new anticancer candidates, particularly those addressing oncogenic mutants, is an urgent medical demand. A campaign of structural modifications has been conducted to further optimize our previously reported 2-anilinoquinoline-diarylamides conjugate VII as a B-RAFV600E/C-RAF inhibitor. Considering the incorporation of a methylene bridge between the terminal phenyl and cyclic diamine, focused quinoline-based arylamides have been tailored, synthesized, and biologically evaluated. Among them, the 5/6-hydroxyquinolines 17b and 18a stood out as the most potent members, with IC50 values of 0.128 µM, 0.114 µM against B-RAFV600E, and 0.0653 µM, 0.0676 µM against C-RAF. Most importantly, 17b elicited remarkable inhibitory potency against the clinically resistant B-RAFV600K mutant with an IC50 value of 0.0616 µM. The putative binding mode of 17b and 18a were studied by molecular docking and molecular dynamics (MD). Moreover, the antiproliferative activity of all target compounds has been examined over a panel of NCI-60 human cancer cell lines. In agreement with cell-free assays, the designed compounds exerted superior anticancer impact over the lead quinoline VII against all cell lines at a 10 µM dose. Notably, both 17b and 18b showed highly potent antiproliferative activity against melanoma cell lines with growth percent under −90% (SK-MEL-29, SK-MEL-5, and UACC-62) at a single dose, while 17b maintained potency with GI50 values of 1.60–1.89 µM against melanoma cell lines. Taken together, 17b, a promising B-RAFV600E/V600K and C-RAF kinase inhibitor, may serve as a valuable candidate in the arsenal of anticancer chemotherapeutics. [ABSTRACT FROM AUTHOR]

This study investigates the effect of annealing temperature on the microstructure, deformation behavior, and mechanical properties of a rolled AZ31 alloy having {10–12} twins. To this end, rolled AZ31 samples are precompressed to 6.0% along the rolling direction (RD) to introduce {10–12} twins and then are annealed at 200, 250, and 300 °C for 1 h. The results reveal that as the annealing temperature increases, the grain size of the annealed samples increases and their RD-oriented basal texture is strengthened. In addition, the number of {10–12} twin boundaries gradually decreases and they almost disappear after annealing at 300 °C. Under tension along the RD, the predominant deformation mechanism of the annealed samples changes from detwinning of preexisting twins to {10–12} twinning as the annealing temperature increases. The annealed samples exhibit different tensile strengths and elongations according to the annealing temperature. Particularly, the tensile elongation increases by 56%, from 13.2% to 20.6%, as the annealing temperature increases from 200 to 300 °C. The variations in the mechanical properties of the annealed samples with the annealing temperature are discussed in detail on the basis of their microstructural characteristics and deformation behaviors. [Display omitted] • A rolled AZ31 alloy is compressed to 6% and then annealed at 200, 250, and 300 °C. • The activation of SIBM during annealing enhances with increasing annealing temperature. • Tensile deformation mechanism of annealed materials varies with annealing temperature. • It changes from detwinning (200) to detwinning + twinning (250) and twinning (300). • Tensile elongation of annealed materials gradually increases with annealing temperature. [ABSTRACT FROM AUTHOR]

The discovery and utility of clinically relevant circulating biomarkers depend on standardized methods that minimize preanalytical errors. Despite growing interest in studying extracellular vesicles (EVs) and cell-free messenger RNA (cf-mRNA) as potential biomarkers, how blood processing and freeze/thaw impacts the profiles of these analytes in plasma was not thoroughly understood. We utilized flow cytometric analysis to examine the effect of differential centrifugation and a freeze/thaw cycle on EV profiles. Utilizing flow cytometry postacquisition analysis software (FCMpass) to calibrate light scattering and fluorescence, we revealed how differential centrifugation and post-freeze/thaw processing removes and retains EV subpopulations. Additionally, cf-mRNA levels measured by RT-qPCR profiles from a panel of housekeeping, platelet, and tissue-specific genes were preferentially affected by differential centrifugation and post-freeze/thaw processing. Critically, freezing plasma containing residual platelets yielded irreversible ex vivo generation of EV subpopulations and cf-mRNA transcripts, which were not removable by additional processing after freeze/thaw. Our findings suggest the importance of minimizing confounding variation attributed to plasma processing and platelet contamination. [ABSTRACT FROM AUTHOR]

Exponential development in artificial intelligence or deep learning technology has resulted in more trials to systematically determine the pathological diagnoses using whole slide images (WSIs) in clinical and nonclinical studies. In this study, we applied Mask Regions with Convolution Neural Network (Mask R-CNN), a deep learning model that uses instance segmentation, to detect hepatic fibrosis induced by N-nitrosodimethylamine (NDMA) in Sprague-Dawley rats. From 51 WSIs, we collected 2011 cropped images with hepatic fibrosis annotations. Training and detection of hepatic fibrosis via artificial intelligence methods was performed using Tensorflow 2.1.0, powered by an NVIDIA 2080 Ti GPU. From the test process using tile images, 95% of model accuracy was verified. In addition, we validated the model to determine whether the predictions by the trained model can reflect the scoring system by the pathologists at the WSI level. The validation was conducted by comparing the model predictions in 18 WSIs at 20× and 10× magnifications with ground truth annotations and board-certified pathologists. Predictions at 20× showed a high correlation with ground truth (R 2 = 0.9660) and a good correlation with the average fibrosis rank by pathologists (R 2 = 0.8887). Therefore, the Mask R-CNN algorithm is a useful tool for detecting and quantifying pathological findings in nonclinical studies. [ABSTRACT FROM AUTHOR]

Natural colorants (anthocyanin and shikonin) were blended in different ratios (3:1 and 1:3) and used for the preparation of carboxymethyl cellulose (CMC)/agar-based functional halochromic films. The colorants were compatible with the polymer matrix and evenly spread over the polymer matrix. The addition of colorants slightly improved the mechanical strength and significantly improved the water vapor barrier properties of CMC/agar-based films without altering the thermal stability. The color indicator film exhibited excellent UV- barrier properties without substantially reducing the transparency. It also showed distinct pH-responsive color-changing properties in the pH range of 2–12, showing excellent acid and base gas sensing properties. The shikonin-added film showed potent antimicrobial activity against food-borne pathogenic bacteria, and the color indicator films exhibited intense antioxidant activities. The CMC/agar-based color indicator films with improved physical and functional properties are likely to be used in active and intelligent food packaging applications. [Display omitted] • Blended colorant of anthocyanin and shikonin was used to fabricate CMC/agar-based film. • Film properties (WVP, WCA, and strength) were improved by adding the colorants. • The film showed a considerable UV-light barrier property with high transparency. • The film showed excellent pH-responsive color-changing and gas sensing properties. • The color indicator film also showed potent antioxidant and antibacterial activities. [ABSTRACT FROM AUTHOR]

Neurogenic claudication is a typical manifestation of lumbar spinal stenosis (LSS). However, its pathophysiology is still unclear. The severity of clinical symptoms has been shown not to correlate with the degree of structural stenosis. Altered cerebrospinal fluid (CSF) flow has been suggested as one of the causative factors of LSS. The objectives of this study were to compare CSF dynamics at the lumbosacral level between patients with LSS and healthy controls and to investigate whether CSF dynamics parameters explain symptom severity in LSS. Phase-contrast magnetic resonance imaging (PC-MRI) was conducted to measure CSF dynamics in 18 healthy controls and 9 patients with LSS. Cephalic peak, caudal peak, and peak-to-peak CSF velocities were evaluated at the lumbosacral level in the patients and controls. The power of CSF dynamics parameters to predict symptom severity was determined using a linear regression analysis adjusted for demographic and structural variables. Significantly attenuated CSF flow velocity was observed in the patients compared with the controls. The cephalic peak, caudal peak, and peak-to-peak velocities at the lumbar level were greater in the controls than in the patients (p<0.001). The predictive power increased most when the peak-to-peak velocity was added (adjusted R2 = 0.410) to the model with age, body mass index, and the minimum anterior-posterior diameter (adjusted R2 = 0.306), and the peak-to-peak velocity was the only statistically significant variable. CSF dynamics variables showed an association with the severity of LSS symptoms, independent of structural stenosis. PC-MRI can help to further our understanding of the pathophysiology of neurogenic claudication and support the diagnosis of LSS. [ABSTRACT FROM AUTHOR]

Although cardiac tissue is considered a target of gravitational force (g-force), the mechanism of hypergravity on the ion modulation or identification of ion transporters is still unknown. Thus, we determine the effect of hypergravity on a physical force-sensitive cytokine, IL-6 and its related channel activity to investigate rat cardiac function changes in response to accelerated g-force. Serum IL-6 levels and intracellular calcium levels of the right atrium were moderately increased under hypergravity stimulation (4g). IL-6 was involved in the modulation of sodium-potassium-chloride cotransporter (Nkcc) activity. Surprisingly, the right atrium under 4g revealed significantly enhanced Nkcc1 activity. The use of IL-6 on the NKCC1-overexpressed or native NKCC-expressing cells also showed enhanced NKCC1 activity. Hypergravity conditions were also involved in the oxidative stress activated Trpm2 channel and revealed an enhanced expression of the Trpm2 channel under 4g in the rat right atrium. In conclusion, hypergravity revealed that moderate increases in serum IL-6 and enhanced Nkcc1 activity was modulated by IL-6. In addition, enhanced Trpm2 channel expression could be involved in the increased intracellular calcium levels of the right atrium under hypergravitational force. We therefore address that enhanced physical force-sensitive cytokine and oxidative stress by the gravitational force mediate activation of the cotransporter involved in possibilities of edema and calcium loading in cardiac tissue. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the surgical and fertility outcomes of reduced port robotic myomectomy (RPRM) using the Da Vinci® Xi™ system as a fertility-preserving surgery. The study included 401 patients who underwent RPRM performed by a single surgeon at a tertiary hospital between October 2017 and October 2021. RPRM required three ports, including a 1.5cm umbilical incision and two 0.8cm incisions located 8cm laterally to the umbilicus. A glove port was utilized through the umbilical incision for scope entry, inserting and removing suture materials, and handling small specimens. The lateral ports were used for tenaculum forceps, bipolar and monopolar forceps, and needle drivers. Fertility outcomes were evaluated through medical records review and follow-up telephone contact. The average age of patients was 39.7 ± 6.0 years. The primary indication was menorrhagia (n=128, 31.9%). On average, 4.7 ± 4.1 (1-22) myomas were removed, with the largest myoma measuring 7.8 ± 2.5 cm (2.5-16). The mean operation time was 103.7 ± 45.6 minutes. Postoperative complications occurred in 9.6% (n=39), mainly transfusions (n=31, 7.7%). Recurrence was evaluated over 1-5 years, revealing a symptomatic recurrence rate of 14.7% (95/401), a median 3.1 cm myoma diameter and 7.4% reoperation rate. Among the 70 patients attempting conception after the surgery, 56 achieved pregnancy either naturally or by assisted reproduction (56/70, 80.0%). The average time interval from surgery to conception was 13.5 ± 10.1 months. Of the 56 pregnancies, 44 resulted in live births (62.9%), five were ongoing (7.1%), and seven ended in miscarriages (10.0%). Cesarean section was performed in the majority of cases (43/44, 97.9%). Eight patients experienced obstetric complications (16.3%), but no uterine rupture was reported. RPRM, offering the advantages of conventional robotic surgery as well as favorable obstetric and cosmetic outcomes, represents a feasible option for patients with symptomatic uterine myomas who desire future conception. [ABSTRACT FROM AUTHOR]

Turquoise hydrogen is produced through a process of separating carbon into solid carbon based on fossil fuels and refers to hydrogen that does not produce carbon dioxide. In this study, the characteristics of turquoise hydrogen production through a methane thermal cracking reaction using an arc plasma torch were investigated. The plasma torch operated stably under high voltage and transport gas flow conditions. The composition of the gas generated from the methane plasma reaction was analyzed using an online IR gas analyzer and GC-FID. The experimental results show that the hydrogen yield decreased to 16.4% as the methane feed rate increased but increased to 58.8% as the plasma power increased. Under these conditions, the yield of solid carbon, a valuable byproduct, was also shown to increase to 62.9%. In addition, solid carbon showed high-temperature heat-treated characteristics based on its generation location. Carbon oxides such as CO and CO2 are rarely generated under any experimental conditions. Consequently, it can be considered that plasma thermal cracking is a promising technology for CO2-free hydrogen production and a valuable solid carbon. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a chronic disease requiring continuous management and is a well-known risk factor for cardiovascular diseases as well as hypertension and diabetes. However, no studies have so far visualized and predicted the probability of dyslipidemia. Hence, this study proposes a nomogram based on a logistic regression model that can visualize its risk factors and predict the probability of developing dyslipidemia. Twelve risk factors for dyslipidemia are identified through a chi-squared test. We then conduct a logistic regression analysis with two interaction variables to obtain a model and build a nomogram for dyslipidemia. Finally, we verify the constructed nomogram using a receiver operation characteristic curve and calibration plot. [ABSTRACT FROM AUTHOR]

Until now, SnO2 nanowires have been directly grown on alumina substrates with Au or Au-coated Pt electrodes by a thermal evaporation method using Sn or SnO2 powders under vacuum. However, in this study, SnO2 nanowires were successfully synthesized on the Pt phase of an alumina substrate by a thermal evaporation method using dibutyltin oxide [DBTO, (C4H9)2SnO] even at atmospheric pressure, resulting in nanowire networks between the Pt phases. Ar with 1% O2 was used as carrier gas with a flow rate of 100 mL/min at 900 °C (heating rate of 25 °C/min). The SnO2 nanowires consisted of straight and branched nanowires, and exhibited a SnO2 phase with a tetragonal structure. Both the DBTO and evaporation temperature play an important role on the synthesis of SnO2 nanowires at atmospheric pressure. The SnO2 nanowire sensor fabricated by an evaporation method showed a sensor response of ~ 500 for 0.05 ppm of NO2, being ~ 10 times greater than that of a SnO2 nanoparticle sensor. Furthermore, the SnO2 nanowire sensor showed excellent repeatability and selectivity for NO2 in the presence of SO2, Cl2, and H2S. [ABSTRACT FROM AUTHOR]

The article discusses a study to examine predictive factors for the rehabilitation of patients with unilateral deafness, including single¿sided deafness (SSD) and asymmetric hearing loss (AHL) through bone¿anchored hearing implants (BAHI) implantation. Topics discussed include the audiological performance of pBAHIs, transcutaneous BAHIs (tBAHIs) without percutaneous abutments and subjective satisfaction in CROS¿tBAHI.

Development of new hole-transport layer (HTL) materials for organic photovoltaic (OPV) applications is one crucial issue to mitigate such limitations of low power efficiency, processibility, and stability derived from poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as a common HTL material. To this end, poly(3-hexylthiophene) (P3HT)-based diblock copolymers including the different ratios between polystyrene (PSty) or/and poly(neopentyl styrene sulfonate) (PNSS) as a second block segment were designed and then used for incorporating with single wall carbon nanotubes (SWCNTs) to form potentially self-dopable nanocomposites. The structure of fabricated P3HT-based diblock copolymer/SWCNT nanocomposites was examined by microscopic and spectroscopic characterizations, exhibiting a charge transfer behavior between P3HT and SWCNT, and growth of the P3HT crystalline phase along the SWCNT surface with a form of the conducting path. The acquired SWCNT nanocomposites exhibited good solubility and dispersion in various organic solvents including toluene, chlorobenzene, THF, chloroform, and DMF, which are good solvents for the PSty or/and PNSS neutral second block. The concept for the neutralized second block by protecting groups can prevent the poisoning ITO substrate by water contamination as shown in the conventional aqueous PEDOT-PSS solution. Notably, the PNSS constituent in the nanocomposite was merely acidified to give in-situ sulfonic acid groups in PSty by simple thermolysis process at 160 °C for 30 min after a solution process for fabrication of a thin film. The thermolysis step provided efficient doping of P3HT by PSS, in which the thiophene groups worked as Brønsted base are protonated by taking protons from sulfonic acid groups and then lead to a form of ionic bonds between cationic thiophene and anionic sulfonate groups. In addition, the formed ionic bonds in the nanocomposites led to an insoluble thin film, which has a good advantage for the further solvent process without substantial damages. The beneficial features of the conducting path along SWCNT and the efficient doping of P3HT by PSS in the acquired nanocomposites led to ca. 5-fold higher electrical conductivity (3.16 S cm−1) and similar work function (5.1 eV) in comparison to water contained commercial PEDOT:PSS (0.6 S cm−1 and 5.0 eV, respectively). As such, the rationally designed potentially self-dopable SWCNT nanocomposites can be one of the promising alternatives beyond the commercial PEDOT: PSS HTL material. [ABSTRACT FROM AUTHOR]

Testing for potential drug interactions of new chemical entities is essential when developing a novel drug. In this study, an assay was designed to evaluate drug interactions with 10 major human cytochrome P450 (P450) enzymes incubated in liver microsomes, involving 12 probe substrates with two cocktail incubation sets used in a single liquid chromatography–tandem mass spectrometry (LC–MS/MS) run. The P450 substrate composition in each cocktail set was optimized to minimize solvent effects and mutual drug interactions among substrates as follows: cocktail A was composed of phenacetin for CYP1A2, bupropion for CYP2B6, amodiaquine for CYP2C8, diclofenac for CYP2C9, S‐mephenytoin for CYP2C19, and dextromethorphan for CYP2D6; cocktail B was composed of coumarin for CYP2A6, chlorzoxazone for CYP2E1, astemizole for CYP2J2, and midazolam, nifedipine, and testosterone for CYP3A. Multiple probe substrates were used for CYP3A owing to the multiple substrate‐binding sites and substrate‐dependent inhibition. After incubation in human liver microsomes, each incubation mixture was pooled and all probe metabolites were simultaneously analysed in a single LC–MS/MS run. Polarity switching was used to acquire the negative‐ion mode for hydroxychlorzoxazone and positive‐ion mode for the remaining analytes. The method was validated by comparing the inhibition data obtained from incubation of each individual probe substrate alone and with the substrate cocktails. The half‐maximal inhibitory concentration values obtained from the cocktail and individual incubations were well correlated and in agreement with previously reported values. This new method will be useful in assessing the drug interaction potential of new chemical entities during new drug development. [ABSTRACT FROM AUTHOR]

Two series of water-soluble metalloporphyrin-cored amphiphilic star block copolymers were synthesized by controlled radical polymerizations such as atom transfer radical polymerization (ATRP) and reversible addition fragmentation chain transfer (RAFT), which gave eight amphiphilic block copolymer arm chains consisting of poly(n-butyl acrylate-b-poly(ethylene glycol) methyl ether methacylate) (PnBA-b-PEGMEMA, Mn,GPC = 78,000, Mw/Mn = 1.2, 70 wt% of PPEGMEMA) and poly(styrene-b-2-dimethylamino ethyl acrylate) (PS-b-PDMAEA, Mn,GPC = 83,000, Mw/Mn = 1.2, 67 wt% of PDMAEA), yielding porphyrin(Pd)-(PnBA-b-PPEGMEMA)8 and porphyrin(Pd)-(PS-b-PDMAEA)8, respectively. Obtained metalloporphyrin polymer photocatalysts were homogeneously solubilized in water to apply to the removal of chlorophenols in water, and was distinguished from conventional water-insoluble small molecular metalloporphyrin photocatalysts. Notably, we found that the water-soluble star block copolymers with hydrophobic-hydrophilic core-shell structures more effectively decomposed the chlorophenol, 2,4,6-trichlorophenol (2,4,6-TCP), in water under visible light irradiation (k = 1.39 h−1, t1/2 = 0.5 h) in comparison to the corresponding water-soluble star homopolymer, because the hydrophobic core near the metalloporphyrin effectively captured and decomposed the hydrophobic chlorophenols in water. [ABSTRACT FROM AUTHOR]

Studies have shown that γ-irradiation induces various biological responses, including oxidative stress and apoptosis, as well as cellular repair and immune system responses. However, most such studies have been performed using traditional two-dimensional cell culture systems, which are limited in their ability to faithfully represent in vivo conditions. A three-dimensional (3D) environment composed of properly interconnected and differentiated cells that allow communication and cooperation among cells via secreted molecules would be expected to more accurately reflect cellular responses. Here, we investigated γ-irradiation–induced changes in the secretome of 3D-cultured keratinocytes. An analysis of keratinocyte secretome profiles following fractionated-dose γ-irradiation revealed changes in genes involved in cell adhesion, angiogenesis, and the immune system. Notably, peroxisome proliferator-activated receptor-α (PPARα) was upregulated in response to fractionated-dose γ-irradiation. This upregulation was associated with an increase in the transcription of known PPARα target genes in secretome, including angiopoietin-like protein 4, dermokine and kallikrein-related peptide 12, which were differentially regulated by fractionated-dose γ-irradiation. Collectively, our data imply a mechanism linking γ-irradiation and secretome changes, and suggest that these changes could play a significant role in the coordinated cellular responses to harmful ionizing radiation, such as those associated with radiation therapy. This extension of our understanding of γ-irradiation-induced secretome changes has the potential to improve radiation therapy strategies. [ABSTRACT FROM AUTHOR]

Understanding metal alloy migration in metal-catalyzed nanowires growth is a prerequisite for improving its potential applications in the field of nanodevices. Here, we explored the surface migration of Au alloys in vertically aligned Si nanowires with different cooling rates. We varied the diameter of Au alloys by controlling the thickness of Au film as a catalyst for SiNW growth, and found that the behavior of Au alloys migration is dependent on size of Au alloys. In addition, the size-dependent migration mechanism of Au alloys was investigated at different cooling rates, which is related to different Au-Si eutectics. [ABSTRACT FROM AUTHOR]

Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer ( n = 581, p = 0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation. [ABSTRACT FROM AUTHOR]

The purpose of this research is to examine the differences of perception between health tour seekers and non-seekers of subjective well-being (SWE). Relative data were collected from 158 Korean package tourists who traveled to Sapporo, Japan, and from 111 Japanese package tourists who traveled to Busan, Korea. The results indicated that health tourism seekers perceived the level of contribution of the health tour to SWE to be more positive than non-seekers. It also revealed that the satisfaction levels of the tourism activities had a partially significant impact on the SWE of participants and non-participants. [ABSTRACT FROM PUBLISHER]

Conclusion: The three-point fix tympanoplasty procedure is a stable and effective technique - with a high degree of graft take and satisfactory hearing results - for reconstruction of most tympanic membrane (TM) perforations. Objective: It is difficult to repair a TM perforation, including subtotal perforation, involving the anterior part of the annulus. Reperforation can occur when an underlay graft technique is used. An overlay graft technique may result in anterior blunting/lateralization. We introduce a three-point fix tympanoplasty procedure, which can provide additional support to yield a stable graft. Methods: The study enrolled a total of 234 patients who underwent a three-point fix tympanoplasty procedure from November 2005 to June 2011. Anatomic success was defined as an intact, repaired TM, while functional success was defined as a significant decrease in the air-bone gap at the end of follow-up compared with preoperative hearing (air-bone gap). The complication rate was also analyzed. Results: The anatomic success rate was 93.2% (218/234 patients). The functional success rate after an average of 1 year was 73.5%. The postoperative average pure-tone air-bone gap (15.4 ± 11.4 dB) decreased successfully in comparison with the preoperative average air-bone gap (20.6 ± 12.1 dB). There were few postoperative complications (7.7%). [ABSTRACT FROM AUTHOR]

A liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometric method (LC–APCI–MS/MS) has been developed for the sensitive determination of antitumor thioproline and methylthioproline from fermented foods. Thioproline and methylthioproline were derivatized in one step with ethyl chloroformate at room temperature. These compounds were identified and quantified in various traditional Korean fermented foods by LC–APCI–MS/MS. The concentration range of thioproline of each food was found for doenjang (0.011–0.032 mg/kg), gochujang (0.010–0.038 mg/kg), and ganjang (0.010–0.038 mg/kg). Those of methylthioproline of each food was found for doenjang (0.098–0.632 mg/kg), gochujang (0.015–0.112 mg/kg), and ganjang (0.023–1.468 mg/kg). A prolonged aging time leads to an increase in both the thioproline and methylthioproline contents, suggesting that the storage time plays a key role in the formation of thioproline and methylthioproline in Korean traditional foods. The results here suggest that thioproline and methylthioproline are related to the biological activities of traditional Korean fermented foods. [ABSTRACT FROM AUTHOR]

Monoamine oxidase-B (MAO-B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) have been considered target enzymes of depression and neurodegenerative diseases, including Alzheimer's disease (AD). In this study, seventeen N-methyl-piperazine chalcones were synthesized, and their inhibitory activities were evaluated against the target enzymes. Compound 2k (3-trifluoromethyl-4-fluorinated derivative) showed the highest selective inhibition against MAO-B with an IC50 of 0.71 μM and selectivity index (SI) of 56.34, followed by 2n (2-fluoro-5-bromophenyl derivative) (IC50 = 1.11 μM, SI = 16.04). Compounds 2k and 2n were reversible competitive MAO-B inhibitors with Ki values of 0.21 and 0.28 μM, respectively. Moreover, 2k and 2n effectively inhibited AChE with IC50 of 8.10 and 4.32 μM, which underscored their multi-target inhibitory modes. Interestingly, compound 2o elicited remarkable inhibitions over MAO-B, AChE, and BChE with IC50 of 1.19–3.87 μM. A cell-based assay of compounds 2k and 2n against Vero normal cells pointed out their low cytotoxicity. In a docking simulation, 2k showed the lowest energy for MAO-B (−11.6 kcal/mol) with four hydrogen bonds and two π-π interactions. Furthermore, in silico studies were conducted, and disclosed that 2k and 2n are expected to possess favorable pharmacokinetic properties, such as the ability to penetrate the blood–brain barrier (BBB). In view of these findings, compounds 2k and 2n could serve as promising potential candidates for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Gelatin/agar-based smart and functional freshness indicator films were fabricated using blue anthocyanin and zinc oxide nanoparticles (ZnO). The anthocyanin was extracted from butterfly pea (Clitoria ternatea) flower, and ZnO was synthesized using a simple hydrothermal method. The butterfly pea anthocyanin (BA) and ZnO were evenly dispersed in the polymer matrix to form a compatible film with the gelatin/agar polymer. The addition of BA and ZnO significantly increased the UV blocking properties and surface hydrophobicity without significant changes in the film's mechanical, thermal stability, and water vapor barrier properties. The BA and BA-added films showed excellent pH-responsive color-change properties as well as good color stability and reversibility. In addition, the composite film showed strong antioxidant and strong bactericidal properties, and the antioxidant function was mainly attributed to the BA, and the antibacterial function was attributed to ZnO. The functional and color indicator film was tested to monitor the freshness of shrimp. It showed distinctive color changes during storage, indicating the degradation of the quality of shrimp accompanied by the total volatile basic nitrogen (TVB-N). [Display omitted] • Gelatin/agar-based color-indicator films integrated with butterfly anthocyanin and ZnO were developed. • The fabricated film showed excellent pH sensitivity and volatile gas sensitivity. • The film showed a significant UV-light barrier property with high transparency. • The film also exhibited good antioxidant and antibacterial activities. • The color indicator films have a high potential for monitoring the freshness of the seafood. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) are toxic and are considered the most important sources for the formation of photochemical smog, secondary organic aerosols (SOAs), and ozone. These can also greatly affect the environment and human health. For this reason, VOCs are removed by applying various technologies or reused after recovery. Catalytic oxidation for VOCs removal is widely applied in the industry and is regarded as an efficient and economical method compared to other VOCs removal technologies. Currently, a large amount of VOCs are generated in industries with solvent-based processes, and the ratio of aromatic compounds is high. This paper covers recent catalytic developments in VOC combustion over noble-metal-based catalysts. In addition, this report introduces recent trends in the development of the catalytic mechanisms of VOC combustion and the deactivation of catalysts, such as coke formation, poisoning, sintering, and catalyst regeneration. Since VOC oxidation by noble metal catalysts depends on the support of and mixing catalysts, an appropriate catalyst should be used according to reaction characteristics. Moreover, noble metal catalysts are used together with non-noble metals and play a role in the activity of other catalysts. Therefore, further elucidation of their function and catalytic mechanism in VOC removal is required. [ABSTRACT FROM AUTHOR]

Conclusion:The dehydration test using isosorbide is well tolerated when used to detect endolymphatic hydrops and may also be used to improve the sensitivity of ECoG performed on patients with MD, especially in poor hearing at low-frequency. Objective:This prospective study was to explore the diagnostic utility of a dehydration test, administering oral isosorbide, which has been used to treat Meniere’s disease (MD). Method:Electrocochleography (ECoG) and the dehydration test with isosorbide were performed on 32 patients diagnosed with definite diagnosed MD. Isosorbide (120 mL) was orally administered after baseline audiometric testing, and the testing was repeated 3 h later. The dehydration test was considered positive when improvements in hearing thresholds of 10 dB or more were evident at two or more frequencies, or the speech discrimination score increased by 12% or more. An abnormal ECoG finding was defined as an SP/AP (summating potential/action potential) ratio ≥0.4. Results:The dehydration test using isosorbide was positive in 10 of 32 patients (31.3%). The test was not associated with development of any serious side-effect. Abnormal ECoG findings were noted in 14 of 32 patients (43.8%). When endolymphatic hydrops was defined as an abnormal ECoG or a positive dehydration test, the condition was detected in 21 of 32 patients (65.6%). The positive result in dehydration test was significantly higher in patients with above moderate hearing loss at low-frequency. [ABSTRACT FROM PUBLISHER]

Abstract: Aims: Danshensu [3-(3,4-dihydroxyphenyl)-lactic acid], a phenylpropanoid compound isolated from Prunella vulgaris var. lilacina, is a well-known antioxidant. Although its antioxidant activity and cardioprotective effect have been reported, the pharmacological properties of danshensu in the central nervous system remain unclear. We investigated whether danshensu exerts anxiolytic-like activity in mice. Main methods: We conducted monoamine oxidase A (MAO-A) inhibition assay on danshensu in vitro, and behavioral tests including the elevated plus-maze test (EPM), the hole-board test, the rotarod test and the open field test were employed. Key findings: We found that danshensu significantly inhibited the activity of MAO-A in vitro. The administration of danshensu (3 or 10mg/kg) produced a significant anxiolytic-like effect in the EPM and hole-board test. In addition, no changes in the spontaneous locomotor activity and no myorelaxant effects were observed compared to the control group; these effects were confirmed with the open field test and the rotarod test. Moreover, the anxiolytic-like properties of danshensu were antagonized by a dopamine D1 receptor antagonist (SCH 23390) but not by a 5-HT1A receptor antagonist (WAY 100635) or an α1-adrenergic receptor antagonist (prazosin). Significance: These results indicate that danshensu exerts its anxiolytic-like properties, in part, through dopaminergic neurotransmitter signaling. [Copyright &y& Elsevier]

A liquid chromatography-electrospray ionization tandem mass spectrometric method (LC-ESI-MS/MS) has been developed for the determination of benzidine (BZ) and 3, 3′-dichlorobenzidine (DCBZ) from surface water. Parent ion of DCBZ gave strong signal with ESI by dissolving with 15 mM ammonium formate, which is also used as mobile phase. Deuterated BZ (d8-BZ) was chosen as the internal standard (IS). BZ and DCBZ were extracted by solid-phase extraction on Oasis hydrophilic-lipophilic balance (HLB) from water at pH 8.0. The coefficients of variation of BZ and DCBZ were less than 13.1% and the detection limits were 0.004 ng L−1for BZ and 0.7 ng L−1for DCBZ using 0.5 L surface water. The detection limit shows fair lower value than the water quality criteria for BZ and DCBZ established by the US EPA. When the proposed method was used to analyze the target compounds in sixteen surface water samples, BZ was detected in a concentration range of 0.15–2.33 ng L−1in four of sixteen surface water samples [ABSTRACT FROM AUTHOR]

The selective hybrid formation of numerous tiny carbon nanofibers (CNFs) in carbon-based nonwoven fabrics (c-NFs), namely CNFs formed only on the surfaces of individual carbon fibers (i-CFs) constituting c-NFs and not on the surfaces of carbon microcoils (CMCs), could be formed by the incorporation of H2 gas flow into the C2H2 + SF6 gas flow in a thermal chemical vapor deposition system. On the other hand, the nonselective hybrid formation of numerous tiny CNFs in c-NFs, that is, tiny CNFs formed on the surfaces of both i-CFs and CMCs, could be achieved by simply modulating the SF6 gas flow on and off in continuous cycles during the reaction. Detailed mechanisms are suggested for the selective or nonselective formation of tiny CNFs in c-NFs. Furthermore, the electromagnetic wave shielding effectiveness (SE) values of the samples were investigated across operating frequencies in the 8.0–12.0 GHz range. Compared with previously reported total SE values, the presently measured values rank in the top tier. Although hybrid formation reduced the electrical conductivity of the native c-NFs, the total SE values of the native c-NFs greatly increased following hybrid formation. This dramatic improvement in the total SE values is ascribed to the increased thickness of c-NFs after hybrid formation and the electromagnetic wave absorption enhancement caused by the intrinsic characteristics of CMCs and the numerous intersections of tiny CNFs. [ABSTRACT FROM AUTHOR]

Highlights: [•] The new analysis method of TSNAs in replacement liquids by LC–MS/MS. [•] First article for the identification and quantification of TSNAs in replacement liquids. [•] The TSNA analytical data in 105 replacement liquids of E-cigarettes. [Copyright &y& Elsevier]

Abstract: A liquid chromatography–tandem mass spectrometry method (LC–MS/MS) was developed in order to determine the bromate in mineral water and table salt. The following optimum conditions for the LC–MS/MS detection were established: derivatization reagent (300mg/L of 2,6-dimethylaniline), acidity (0.2M HCl), reaction temperature (30°C) and heating time (20min). The formed derivative was directly injected in the LC system without extraction or purification procedures. In the established conditions, the method was used to detect bromate in mineral water and table salt. The limit of detection and limit of quantification of bromate in mineral water were 0.02μg/L and 0.07μg/L, respectively, and those of table salt were 0.07μg/kg and 0.23μg/kg, respectively. The 17 common ions did not interfere even when present in 1,000-fold excess over the bromated ion of 10.0μg/L. The accuracy was in a range of 92–104% and the assay precision was less than 9% in the table salt. The method was successfully applied to determine bromate in mineral water and table salt. [Copyright &y& Elsevier]

Abstract: Ethonopharmacological relevance: Cortex Mori Radicis (CMR), the root epidermis of Morus alba L., has been traditionally used for cough treatment in Oriental medicine. In the present study, immunological mechanism of CMR in inhibition of airway hyperresponsiveness (AHR) was investigated in a mouse asthma model. Materials and methods: Experimental asthma model was established in Balb/c mice sensitized by ovalbumin (OVA), followed by aerosol allergen challenges. CMR (50 or 200mg/kg) was orally administered for 6-weeks from 3-weeks after OVA sensitization. AHR, pulmonary eosinophilic accumulation, immunoglobulin E (IgE), histamine, Th2 cytokine expression, and CD4+CD25+Foxp3+ regulatory T cells (Tregs) were evaluated by flow cytometry, enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Results: CMR significantly reduced AHR response, eosinophil infiltration, and production of serum histamine and OVA-specific IgE. Furthermore, CMR suppressed Th2 cytokines such as interleukin (IL)-4, -5 and -13 at protein (secreted) and mRNA levels. Of note, CMR significantly increased Foxp3+ Tregs population and enhanced Foxp3+ mRNA expression in a mouse asthma model. Conclusions: CMR exerts anti-allergic effect via enhancement of CD4+CD25+Foxp3+ regulatory T cells and inhibition of Th2 cytokines in a mouse asthma model as a potent anti-asthmatic agent. [Copyright &y& Elsevier]

Regioregular poly(3-hexyl thiophene) ( rr-P3HT)-based star polymers were synthesized by a crosslinking reaction of the linear rr-P3HT macroinitiator and ethylene glycol dimethacrylate (EGDMA) crosslinker through Ru-based atom transfer radical polymerization (ATRP), where the rr-P3HT macroinitiator was prepared by Grignard metathesis method (GRIM) followed by end functionalization of the ATRP initiator with chlorophenylacetate (CPA) to the rr-P3HT. Relatively high molecular weight of the star polymers were obtained ( Mp = 8,988,000 g/mol), which consisted of large numbers of the rr-P3HT arm chains radiating from the EGDMA-based microgel core. The yield of the star polymers were strongly affected by the added amount of the EGDMA crosslinker. The crystalline structure of the rr-P3HT by intermolecular π-π stacking interaction gradually decreased as the star polymer formed, which was confirmed by differential scanning calorimeter (DSC), atomic force microscopy (AFM), and electro-optical analyses. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011 [ABSTRACT FROM AUTHOR]

Abstract: We describe a simple derivatization method to determine aldehydes. This method is based on derivatization with d-cysteine and consecutive liquid chromatography–tandem mass spectrometry (LC–MS/MS). The optimum derivatization conditions of aldehydes with d-cysteine were 10min at 50°C and pH 7.0. The formed alkyl thiazolidine-4-carboxylic acid derivatives were directly injected in LC–MS/MS. In the established condition, the method was used to detect eight aldehydes in beverages. The limit of detection (LOD) and limit of quantification (LOQ) of the aldehydes were 0.2–1.9μgL−1 and 0.7–6.0μgL−1 and the relative standard deviation was less than 2.0% at concentrations of 0.1mgL−1 and 1.0mgL−1 with the exception of octanal. All the beverage samples had detectable levels of methanal (0.033–0.145mgL−1), ethanal (0.085–2.12mgL−1), propanal (ND to 0.250mgL−1), butanal (ND to 0.003mgL−1), pentanal (ND to 0.471mgL−1), hexanal (ND to 0.805mgL−1), heptanal (0.019–3.91mgL−1) and octanal (0.029–0.118mgL−1). [Copyright &y& Elsevier]

Transforming growth factor-β (TGF-β) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. βig-h3 is an extracellular matrix protein which is induced in many cells by TGF-β. This study examined urinary βig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary βig-h3 as a marker of diabetic nephropathy. Urinary and serum βig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary βig-h3 and TGF-β to creatinine was analyzed in patients with different degree of nephropathy. The βig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6±9.27), microalbuminuria (120.2±14.48), and overt proteinuria (146.3±16.34), when compared with control subjects (64.8±7.14) (P<0.01). There was a positive correlation between urinary βig-h3 and TGF-β excretion rate and a positive correlation between urinary βig-h3 and albumin excretion rate (AER). These data show that urinary levels of βig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy. [Copyright &y& Elsevier]

Purpose: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. Methods: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. Results: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. Conclusions: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients. [ABSTRACT FROM AUTHOR]

Isobaric vapor-liquid equilibrium data were measured for the two binary systems of 2-methyl-1-pentanol + 2,3-butanediol and 3-methyl-1-butanol + 2,3-butanediol using a modified Othmer still VLE apparatus at 40, 60, 80 and 101 kPa. The standard uncertainty of the pressure and temperature was 0.13 kPa and 0.1 K, respectively. To assess the thermodynamic consistency of the experimental data, Herington area test method and Van Ness-Byer-Gibbs test method have been used. The experimental data were also correlated with the two activity coefficient models, NRTL and UNIQUAC, and the binary parameters for the models have been calculated. For the quantitative analysis of the experimental data, we used the root-mean-square deviation (RMSD) and the average absolute deviation of the temperature (AAD-T) and the vapor-phase composition (AAD-y). Overall AAD-y were 4 × 10−4 (NRTL) and 5 × 10−4 (UNIQUAC) for 2-methyl-1-pentanol + 2,3-butanediol system, and 5 × 10−4 (NRTL) and 6 × 10−4 (UNIQUAC) for 3-methyl-1-butanol + 2,3-butanediol system, respectively. This test results support the validity of the models used for the two binary systems studied in this work. [ABSTRACT FROM AUTHOR]

Sulfur nanoparticles (SNPs) were prepared and embedded in calcium cross-linked alginate films in varying concentration, and their effect on the functional properties of the films were studied. The FE-SEM image showed uniform dispersion of up to 2 wt% of SNPs, above which aggregation was observed. The addition of 2 wt% of SNPs showed the best results of the tensile and water vapor barrier properties, with an increase in 12% and 41%, respectively. The surface color of the films changed significantly by the addition of SNPs with a decrease in transparency. However, the UV barrier properties showed a considerable increase of 99%. In addition, the incorporation of SNPs increased the hydrophobicity of the film, which was evident by the increased water contact angle and decreased moisture content of the film, as indicated by the thermal analysis results. The antimicrobial activity of alginate/SNPs composite film was tested against foodborne pathogenic bacteria, E. coli and L. monocytogenes. The nanocomposite film did not completely destroy E. coli but showed a bacteriostatic activity to reduce the 60% of bacterial colonies. However, the activity against L. monocytogenes was found to be highly bactericidal at the highest nanoparticle concentration, where a 100% bacterial elimination was observed after 12 h of exposure. Thus, the alginate/SNPs composite film can be used for the packaging of frozen foods with high moisture content that are susceptible to Listeria monocytogenes contamination, such as meat products. Image 1 • Active alginate films incorporated with sulfur nanoparticles (SNPs) were fabricated. • Films with 2% (w/w) SNPs displayed best barrier and mechanical properties. • The films indicated high UV-barrier properties with 99% reduced UV transmittance. • The films were highly bactericidal against meat spoiling bacteria L. monocytogenes. • Packaging of frozen meat products can be a possible application of the films. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the leading causes of death in cancer patients. Epithelial-mesenchymal transition (EMT) plays an important role in lung cancer progression. Therefore, for lung cancer treatment, it is crucial to find substances that inhibit EMT. Ethacrynic acid (ECA) is a diuretic that inhibits cellular ion flux and exerts anticancer effects. However, the effects of ECA on EMT in lung cancer remain unclear. We examined the effects of ECA on sphingosylphosphorylcholine (SPC) or TGF-β1-induced EMT process in A549 and H1299 cells via reverse transcription polymerase chain reaction and Western blotting. We found that ECA inhibited SPC-induced EMT and SPC-induced WNT signalling in EMT. We observed that SPC induces the expression of NDP [Norrie disease protein] and WNT-2, whereas ECA suppressed their expression. SPC-induced WNT activation, EMT, migration, and invasion were suppressed by NDP small-interfering RNA (siNDP), but NDP overexpression (pNDP) enhanced these events in A549 and H1299 cells. Accordingly, NDP expression may influence lung cancer prognosis. In summary, our results revealed that ECA inhibited SPC or TGF-β1-induced EMT in A549 and H1299 lung cancer cells by downregulating NDP expression and inhibiting WNT activation. Therefore, ECA might be a new drug candidate for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Many emerging technologies are reliant on circulating cell-free DNA (cfDNA) and cell-free RNA (cfRNA) applications in the clinic. However, the impact of diurnal cycles or daily meals on circulating analytes are poorly understood and may be confounding factors when developing diagnostic platforms. To begin addressing this knowledge gap, we obtained plasma from four healthy donors serially sampled five times during 12 h in a single day. For all samples, we measured concentrations of cfDNA and cfRNA using both bulk measurements and gene-specific digital droplet PCR. We found no significant variation attributed to blood draw number for the cfDNA or cfRNA. This indicated that natural diurnal cycles and meal consumption do not appear to significantly affect abundance of total cfDNA, total cfRNA, or our two selected cfRNA transcripts. Conversely, we observed significant variation between individual donors for cfDNA and one of the cfRNA transcripts. The results of this work suggest that it will be important to consider patient-specific baselines when designing reliable circulating cfDNA or cfRNA clinical assays. [ABSTRACT FROM AUTHOR]

The liquid–liquid equilibriums (LLE) in two ternary systems, {water + 2,3-butanediol + 2-methyl-1-pentanol} and {water + 2,3-butanediol + 3-methyl-1-butanol}, were studied at three temperatures, 298.2 K, 308.2 K, and 318.2 K. To complete the phase diagram, the LLE data and solubility data were obtained. To select a suitable solvent, distribution coefficient (D) and selectivity (S) were calculated. The values of D and S of 2-methyl-1-pentanol were (0.36–0.67) and (3.29–7.97) and those of 3-methyl-1-butanol were (0.44–0.95) and (2.29–5.80), respectively. Compared to the values of previously reported solvents, the values of D and S of 3-methyl-1-butanol were relatively higher. Nonrandom two liquids (NRTL) model was used to correlate the experimental data. All root mean square deviation (RMSD) values were 0.0166 in average, which indicates successful correlations between the experimental data and those obtained from the NRTL model. [ABSTRACT FROM AUTHOR]

H2 plasma treatment was performed on carbon-based nonwoven fabrics (c-NFs) in a 900 W microwave plasma-enhanced chemical vapor deposition system at 750 °C and 40 Torr. Consequently, the electromagnetic wave shielding effectiveness (SE) of the c-NFs was significantly enhanced across the operating frequency range of 0.04 to 20.0 GHz. We compared the electromagnetic wave SE of the H2 plasma-treated c-NFs samples with that of native c-NFs samples coated with nano-sized Ag particles. Despite having a lower surface electrical conductivity, H2 plasma-treated c-NFs samples exhibited a considerably higher electromagnetic wave SE than the Ag-coated c-NFs samples, across the relatively high operating frequency range of 7.0 to 20.0 GHz. The carbon component of H2 plasma-treated c-NFs samples increased significantly compared with the oxygen component. The H2 plasma treatment transformed the alcohol-type (C–O–H) compounds formed by carbon-oxygen bonds on the surface of the native c-NFs samples into ether-type (C–O–C) compounds. On the basis of these results, we proposed a mechanism to explain the electromagnetic wave SE enhancement observed in H2 plasma-treated c-NFs. [ABSTRACT FROM AUTHOR]

• Development of a GC–MS method to screen 53 PDE-5i drugs in dietary supplements. • Microscale sample preparation combined with simple LLE and trimethylsilylation. • First description of characteristic common EI fragment ions of PDE-5i TMS derivatives. • Construction of ECICs and discriminant analysis (DA) based on specific common ions. • Reliable screening and classification of PDE-5i in supplements using ECICs and DA. Illegal dietary supplements adulterated with phosphodiesterase type 5 inhibitors (PDE-5i) are increasingly widely distributed through internet markets and underground routes. For this reason, it demands development of reliable screening methods to determine a wide range of PDE-5i drugs in various types of dietary supplements. Herein, we developed a screening method using gas chromatography-mass spectrometry (GC–MS) for simultaneous detection of 53 PDE-5i drugs in supplements. Common formulations (such as capsule, powder, pill, and tablet) of supplements with complicated matrices were treated by simple liquid–liquid extraction and trimethylsilyl (TMS) derivatization. With the aid of TMS derivatization, 53 PDE-5i drugs could be successfully separated and detected within 15 min, using a short microbore GC column (15 m). Moreover, owing to enhanced detection sensitivity and selectivity of PDE-5i TMS derivatives, 0.5 mg of sample was sufficient to screen and confirm targeted PDE-5i drugs. In this study, specific common ions according to structural characteristics of PDE-5i drugs were found under the electron ionization (EI) of their TMS derivatives. These specific common fragments could reflect the common pharmacophores for 4 classes of PDE-5i drugs (sildenafil, other sildenafil, vardenafil, and tadalafil analogues). Based on characteristic EI fragment ions, extracted common ion chromatograms (ECICs) and discriminant analysis (DA) were effectively used for reliable screening and classification of various types of PDE-5i drugs. Specific ECICs and DA using characteristic EI fragments here will aid in identification of newly emerging PDE-5i counterfeits in supplements. This study will be helpful to supervise illegal adulteration of PDE-5i drugs in dietary supplements to protect public health and consumer safety. [ABSTRACT FROM AUTHOR]

[Display omitted] • New coumarin benzamides 3a – j were designed and synthesized. • Selective MAO-B inhibition (IC 50 = 95 nM, K i = 46 nM) was elicited by compound 3i. • The 6-amidocoumarins 3i and 3j showed a safe cytotoxicity profile. • Compounds 3i and 3j showed neuroprotective effects in SH-SY5Y neuroblastoma cells. • Docking and MD simulations highlighted the favorable binding mode of 3i with MAO-B. A series of new 6-amidocoumarin derivatives, 3a – j, was synthesized and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase. All compounds, except 3 g , showed higher inhibitory activity towards MAO-B than MAO-A. Compound 3i most potently inhibited MAO-B with an IC 50 value of 0.095 μM, followed by 3j (0.150 μM), 3b (0.190 μM), and 3c (0.204 μM). Compound 3i demonstrated the highest selectivity index (>421.05) for MAO-B. The remarkable MAO-B inhibitory activity of compounds 3i , 3j , 3b , and 3c highlighted the substantial role of the substituents at the 3,4-position of the terminal phenyl group in achieving optimal MAO-B inhibition, especially 3-Cl (3i) > 3-CF 3 (3b). In the kinetic study, the K i value of 3i for MAO-B was 0.046 ± 0.010 μM with a competitive reversible mode. Moreover, compounds 3i and 3j were nontoxic to normal (MDCK), cancer (HL-60), and neuroblastoma (SH-SY5Y) cells and showed protective effects against damage induced by reactive oxygen species in SH-SY5Y neuroblastoma cells. Moreover, molecular docking and molecular dynamics simulations highlighted the tight interactions of 3i with Tyr398 at the binding site of MAO-B. These findings suggest that 3i is a potent, reversible, and selective MAO-B inhibitor that could potentially treat neurological disorders. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the human SCN5A gene encoding the a-subunit of the principle Na+ channel (Nav1.5) are associated with long QT syndrome (LQTS) 3. LQT3 patients display variable responses to Na+ channel blockers demanding for the development of variant-specific therapeutic strategies. Here we performed a combined electrophysiological analysis with in silico simulation of variant channel to elucidate mechanisms of therapeutic responsiveness. We identified a novel SCN5A variant (A1656D) in a LQTS patient with a distinct response to mexiletine resulting in suppression of non-sustained ventricular tachycardia and manifestation of premature atrial contraction. Patch clamp analysis revealed that A1656D variant exerted gain-of-function effects including hyperpolarizing shift of the voltage-dependence of activation, depolarizing shift in the voltage-dependence of inactivation, and slowing of fast inactivation. Among ranolazine, flecainide, and mexiletine, only mexiletine restored inactivation kinetics of A1656D currents. In silico simulation to assess the effect of A1656D variant on ventricular cardiac cell excitation predicted a prolonged action potential which is consistent with the prolonged QT and non-sustained ventricular tachycardia of the patient. It also predicted that only mexiletine suppressed the prolonged action potential of human ventricular myocytes expressing A1656D. These data elucidate the underlying mechanism of the distinct response to mexiletine in this patient. [ABSTRACT FROM AUTHOR]