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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]

In the process of pyrolyzing waste plastics, the generation of Cl2 gas can pose a problem. During the pyrolysis processing, incomplete combustion of organic compounds containing chlorine can lead to the formation of toxic chemicals, which can cause issues in subsequent processing stages. Therefore, an adsorbent plays an important role in removing Cl2 in the dechlorination process, and alkaline adsorbents and metal oxides are generally used. Waste red mud is composed of Fe metal oxide and alkaline components, so it is intended to be used as a Cl2 adsorbent. The Cl2 removal ability of red mud with different redox status of iron oxides was assessed. Hydrogen treatment was performed at various temperatures to control the reduction potential of the Fe in the metal oxides, and phase changes in the Fe oxide component of red mud were confirmed. In the case of red mud hydrogenated at 700 °C, most of the Fe2O3 structure could be converted to the Fe3O4 structure, and the Fe3O4 structure showed superior results in Cl2 adsorption compared to the Fe2O3 structure. As a result, red mud at an H2 treatment temperature of 700 °C showed about three times higher Cl2 adsorption compared to red mud without H2 treatment. [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]

A new series of 3,4,5-trimethoxyphenyl thiazole pyrimidines has been synthesized and biologically evaluated for its in vitro anticancer activity. Compounds 4a, 4b, and 4h with substituted piperazine showed the best antiproliferative activity. In the NCI-60 cell line screening, compound 4b showed promising cytostatic activity against multiple cell lines. Notably, it elicited a GI value of 86.28% against the NSCL cancer cell line HOP-92 at a 10 μM dose. Compounds 4a and 4h at 10 μM showed promising GI values of 40.87% and 46.14% against HCT-116 colorectal carcinoma and SK-BR-3 breast cancer cell lines, respectively. ADME-Tox prediction of compounds 4a, 4b, and 4h revealed their acceptable drug-likeness properties. In addition, compounds 4a, 4b, and 4h showed a high probability of targeting kinase receptors via Molinspiration and Swiss TargetPrediction. [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]

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]

Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer's disease, Parkinson's disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases. [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]

As climates change around the world, concern regarding environmental pollutants emitted into the atmosphere is increasing. The cement industry consistently produces more than 4000 million metric tons of cement per year. However, the problem of air pollutants being emitted from the calcination process is becoming more critical because their amount increases proportionally with cement production. Each country has established regulatory standards for pollutant emission. Accordingly, the cement industry is equipped with facilities to reduce air pollutants, one of which is the NOx removal process. NOx reduction processes under combustion conditions are modified to minimize NOx generation, and the generated NOx is removed through post-treatment. In terms of NOx removal efficiency, the post-treatment process effectively changes the combustion conditions during calcination. Selective non-catalytic reduction (SNCR) and selective catalytic reduction (SCR) processes are post-treatment environmental facilities for NOx reduction. Accordingly, considering the stringent NOx emission standards in the cement industry, SNCR is essential, and SCR is selectively applied. Therefore, this paper introduces nitrogen oxide among air pollutants emitted from the South Korean cement industry and summarizes the technologies adapted to mitigate the emission of NOx by cement companies in South Korea. [ABSTRACT FROM AUTHOR]

ARG2 has been reported to inhibit autophagy in vascular endothelial cells and keratinocytes. However, studies of its mechanism of action, its role in skin fibroblasts, and the possibility of promoting autophagy and inhibiting cellular senescence through ARG2 inhibition are lacking. We induced cellular senescence in dermal fibroblasts by using H2O2. H2O2-induced fibroblast senescence was inhibited upon ARG2 knockdown and promoted upon ARG2 overexpression. The microRNA miR-1299 suppressed ARG2 expression, thereby inhibiting fibroblast senescence, and miR-1299 inhibitors promoted dermal fibroblast senescence by upregulating ARG2. Using yeast two-hybrid assay, we found that ARG2 binds to ARL1. ARL1 knockdown inhibited autophagy and ARL1 overexpression promoted it. Resolvin D1 (RvD1) suppressed ARG2 expression and cellular senescence. These data indicate that ARG2 stimulates dermal fibroblast cell senescence by inhibiting autophagy after interacting with ARL1. In addition, RvD1 appears to promote autophagy and inhibit dermal fibroblast senescence by inhibiting ARG2 expression. Taken together, the miR-1299/ARG2/ARL1 axis emerges as a novel mechanism of the ARG2-induced inhibition of autophagy. Furthermore, these results indicate that miR-1299 and pro-resolving lipids, including RvD1, are likely involved in inhibiting cellular senescence by inducing autophagy. [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]

LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchymal transition (EMT) of lung cancer cells. A549 and H1299 lung cancer cells were induced to undergo via TGF-β1 treatment, resulting in the downregulation of E-cadherin and upregulation of N-cadherin and Vimentin concurrently with increases in the migration and invasion capacities of the cells. These effects of TGF-β1 were suppressed upon co-treatment of the cells with LW1497. An RNA-seq analysis revealed that LW1497 induced differential expression of genes related to hypoxia, RNA splicing, angiogenesis, cell migration, and metastasis in the A549 lung cancer cell lines. We confirmed the differential expression of Slug, an EMT-related transcription factor. Results from Western blotting and RT-PCR confirmed that LW1497 inhibited the expression of EMT markers and Slug. After orthotopically transplanting A549 cancer cells into mice, LW1497 was administered to examine whether the lung cancer progression was inhibited. We observed that LW1497 reduced the area of cancer. In addition, the results from immunohistochemical analyses showed that LW1497 downregulated EMT markers and Slug. In conclusion, LW1497 suppresses cancer progression through the inhibition of EMT by downregulating Slug. [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]

This study was conducted using the database of the Korea National Health and Nutrition Examination Survey to determine whether age-related eye diseases such as cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are related to hearing loss. 12,899 participants ≥ 40 years of age were included. The weighted prevalence of diabetic retinopathy was not significantly different between the normal hearing group and hearing-impaired group, but the weighted prevalences of cataract, glaucoma, early AMD, and late AMD were significantly different in the two groups. The odds ratio for cataract in the hearing-impaired group was 1.373 (1.118–1.687). The odds ratios of glaucoma, DR, early AMD, and late AMD were not significantly different in the hearing-impaired group. Age was significantly associated with the presence of concurrent cataract and hearing impairment by 6.574-fold per decade. Significant factors that increased the risk of concurrent glaucoma and hearing impairment were age, male gender, and triglyceride. Age, ex-smoker, systolic BP elevation, BMI decline, and fasting blood sugar significantly predicted the presence of concurrent DR and hearing loss. In early AMD, age and triglyceride, and in late AMD, age and systolic BP elevations increased the risk of concurrent AMD and hearing impairment. [ABSTRACT FROM AUTHOR]

Carbon fiber-carbon microcoil (CF-CMC) hybrids were formed on carbon fiber (CF)-based fabric. The morphologies of CF-based fabrics and CF-CMC hybridized fabrics were investigated. The electrical conductivities of the CF-CMC hybridized fabrics were examined and compared with those of native CF-based fabrics. Furthermore, the electromagnetic wave shielding effectiveness (SE) of the CF-CMC hybridized fabrics was investigated across operating frequencies in the 8.0–12.0 GHz range, and the results were compared with those for native CF-based fabrics. For the CF-based nonwoven fabrics, the SE values were improved by the CF-CMC hybridization reaction, although the electrical conductivities of the nonwoven fabric were reduced by the CF-CMC hybrid formation. For the CF-based woven fabrics, the SE values were improved by more than twofold throughout the entire range of frequencies, owing to the CF-CMC hybrid formation. This dramatic improvement was partly ascribed to the enhanced electrical conductivity, particularly in the transverse direction to the individual CFs. Owing to the increased thickness of the woven or nonwoven fabrics after the CF-CMC hybrid formation and the intrinsic characteristics of CMCs, the absorption mechanism for the SE was determined for the main factor that contributed to the improvement of the SE values. [ABSTRACT FROM AUTHOR]

A rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of organic anion transporting polypeptide 1B1 (OATP1B1) and cytochrome P450 (P450) probe substrates and their phase I metabolites in human plasma was developed. The OATP1B1 (pitavastatin) and five P450 probe substrates, caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A) and their metabolites were extracted from human plasma (50 µL) using methanol. Analytes were separated on a C18 column followed by selected reaction monitoring detection using MS/MS. All analytes were separated simultaneously within a 9 min run time. The developed method was fully validated over the expected clinical concentration range for all analytes tested. The intra- and inter-day precisions for all analytes were lower than 11.3% and 8.82%, respectively, and accuracy was 88.5–117.3% and 96.1–109.2%, respectively. The lower limit of quantitation was 0.05 ng/mL for dextromethorphan, dextrorphan, midazolam, and 1′-hydroxymidazolam; 0.5 ng/mL for losartan, EXP-3174, omeprazole, 5′-hydroxyomeprazole, and pitavastatin; and 5 ng/mL for caffeine and paraxanthine. The method was successfully used in a pharmacokinetic study in healthy subjects after oral doses of five P450 and OATP1B1 probes. This analytical method provides a simple, sensitive, and accurate tool for the determination of OATP1B1 and five major P450 activities in vivo drug interaction studies. [ABSTRACT FROM AUTHOR]

Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study. In each sample, the keratinocytes were isolated and cultured, and the intracellular Ca 2+ level at the time of stimulation of each factor was quantified and the interaction was screened. PAR2 function was reduced by antagonism of TRPV3. Inhibiting protein kinase A (PKA) and protein kinase C (PKC) reduced TRPV3 function. TSLP mRNA and protein, and TSLPR protein expressions, increased in scars with post-burn pruritus, compared to scars without it or to normal tissues. In addition, TRPV1 or TRPV3 activation induced increased TSLP expression. Conclusively, TRPV3 may contribute to pruritus in burn scars through TSLP, and can be considered a potential therapeutic target for post-burn pruritus., Competing Interests: The authors declare no conflicts of interest.