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In recent years, the rapid development of genetically modified (GM) technology has raised concerns about the safety of GM crops and foods for human health and the ecological environment. Gene flow from GM crops to other crops, especially in the Brassicaceae family, might pose a threat to the environment due to their weediness. Hence, finding reliable, quick, and low-cost methods to detect and monitor the presence of GM crops and crop products is important. In this study, we used visible near-infrared (Vis-NIR) spectroscopy for the effective discrimination of GM and non-GM Brassica napus, B. rapa, and F1 hybrids (B. rapa X GM B. napus). Initially, Vis-NIR spectra were collected from the plants, and the spectra were preprocessed. A combination of different preprocessing methods (four methods) and various modeling approaches (eight methods) was used for effective discrimination. Among the different combinations, the Savitzky-Golay and Support Vector Machine combination was found to be an optimal model in the discrimination of GM, non-GM, and hybrid plants with the highest accuracy rate (100%). The use of a Convolutional Neural Network with Normalization resulted in 98.9%. The same higher accuracy was found in the use of Gradient Boosted Trees and Fast Large Margin approaches. Later, phenolic acid concentration among the different plants was assessed using GC-MS analysis. Partial least squares regression analysis of Vis-NIR spectra and biochemical characteristics showed significant correlations in their respective changes. The results showed that handheld Vis-NIR spectroscopy combined with chemometric analyses could be used for the effective discrimination of GM and non-GM B. napus, B. rapa, and F1 hybrids. Biochemical composition analysis can also be combined with the Vis-NIR spectra for efficient discrimination.

Background Next‐generation sequencing has mostly been used for genotyping cell‐free DNA (cfDNA) in plasma. However, this assay has several clinical limitations. We evaluated the clinical utility of a novel polymerase chain reaction–free nanowire (NW)‐based plasma cfDNA assay for detecting ALK fusion and mutations. Patients, Materials, and Methods We consecutively enrolled 99 patients with advanced non‐small cell lung cancer undergoing a fluorescence in situ hybridization (FISH) test for ALK fusion; ALK‐positive (n = 36). The NW‐based assay was performed using 50–100 μL of plasma collected at pretreatment and every 8 weeks during ALK inhibitor treatment. Results There was high concordance between the NW‐based assay and the FISH test for identification of ALK fusion (94.9% with a kappa coefficient value of 0.892, 95% confidence interval [CI], 0.799–0.984). There was no difference in the response rate to the first anaplastic lymphoma kinase inhibitor between the ALK‐positive patients identified by the NW‐based assay and by the FISH test (73.5% vs. 72.2%, p = .931). In the ALK variant analysis, variants 1 and 3 subgroups were detected in 27 (75.0%) and 8 (22.2%) patients, respectively. Among 24 patients treated with crizotinib, variant 3 subgroup was associated with worse median overall survival than variant 1 subgroup (36.5 months; 95% CI, 0.09–87.6 vs. 19.8 months; 95% CI, 9.9–not reached, p = .004]. A serial assessment identified that ALK L1196M resistance mutation emerged before radiologic progression during crizotinib treatment. Conclusion The newly developed simple NW‐based cfDNA assay may be clinically applicable for rapid diagnosis of ALK fusion with its variant forms and early detection of resistance. Implications for Practice The authors developed a novel one‐step polymerase chain reaction–free nanowire (NW)‐based plasma cell‐free DNA (cfDNA) assay. This study evaluated the clinical utility of this novel method for the diagnosis of EML4‐ALK fusion in advanced non‐small cell lung cancer (NSCLC). The NW‐based assay and FISH test showed high concordance rate in 99 patients with advanced NSCLC. Serial cfDNA assessment demonstrated this method provided early detection of resistance before radiologic progression during crizotinib treatment. Taken together, plasma cfDNA genotyping by the NW‐based cfDNA assay may be useful for the rapid diagnosis of ALK fusion, classifying variants, and early detection of resistance., This article describes a novel one‐step polymerase chain reaction–free nanowire‐based plasma cell‐free DNA assay and evaluates the clinical utility of this novel method for the diagnosis of EML4‐ALK fusion in advanced non‐small cell lung cancer.

Background Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. Methods This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. Results Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. Conclusion Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

We profiled and quantified primary (amine, organic acids, tricarboxylic acid cycle intermediates, amino acids, and carbohydrates) and secondary metabolites (triterpenoids, phenolic acids, carotenoids, flavonoids, and anthocyanins) in the edible parts (leaves and fruits) of the diploid and tetraploid cultivar Morus alba L. 'Cheongil.' Through comprehensive metabolic profiling, the tetraploid mulberry cultivar was able to produce diverse metabolites supported by higher accumulation patterns of primary and secondary metabolites in their edible parts. In particular, the edible parts of the tetraploid showed higher accumulation patterns of most metabolites (amino acids, carbohydrates, carotenoids, and anthocyanins) than the diploid, which was supported by the results of principal component analyses (PCAs) showing a clear separation between the diploid and tetraploid groups. Additionally, this metabolome study comprehensively described the correlation between primary and secondary metabolites in the edible parts of diploid and tetraploid mulberry cultivars and provided information useful for plant breeding strategies to improve metabolite biosynthesis using polyploidy.

We profiled and quantified primary and secondary metabolites in the leaves and roots of xBrassicoraphanus (Baemuchae), Brassica campestris ssp. pekinensis (Chinese cabbage), and Raphanus sativus (radish). We obtained 72 metabolites from leaves and 68 metabolites from both leaves and roots of xBrassicoraphanus, Chinese cabbage, and radish. The metabolic profiles in this study revealed intermediate-level production of most metabolites from different parts of Baemuchae compared with that from different parts of Chinese cabbage and radishes. This was supported by the results of principal component analyses for the detected metabolites, which indicated that the Baemuchae group was located between the Chinese cabbage and radish groups. In particular, several amino acids (phenylalanine, tryptophan, and methionine) played the main role in phenylpropanoid and glucosinolate biosynthesis and were positively correlated with phenolic compounds, indolic glucosinolates, and aliphatic glucosinolates, respectively, in different parts. Furthermore, analysis of different species revealed the presence of 10 different glucosinolates, 10 phenolics, and 7 carotenoids, and their levels varied in the roots and leaves of the studied species. Among the leaves of the three species, Chinese cabbage had the highest total glucosinolate level, which was 3.14 times higher than the lowest level observed in radish. Baemuchae had the highest total phenolic compound level, which was 2.87 times higher than the lowest level found in Chinese cabbage, and radish had the highest carotenoid level, which was 12.41 times higher than the lowest one observed in Chinese cabbage. In the roots of Baemuchae, Chinese cabbage, and radish, glucosinolate levels did not vary significantly. Chinese cabbage contained the highest total phenolic compound level, which was 2.38 times higher than the lowest level found in radish, and the highest total carotenoid level, which was 2.49 times higher than the lowest level observed in Baemuchae. This metabolomic study provided chemical composition information that can be applied to future breeding strategies and comprehensively described the relationship among metabolites detected in the three plant species.

Purpose: In this study, we aim to study the functionality of multiple effects of peptide collagen and naturally derived compounds through in vitro experiments and human application tests. Method: Cytotoxicity of inner beauty film (IBF), pro-collagen generation ability, elastase and collagenase inhibition, DPPH radical scavenging and tyrosinase inhibition ability were measured, and skin improvement, through in vitro and human application test. Results: Cytotoxicity was not confirmed up to 1000 μg/mL. Elastase inhibition was 7.2% at a concentration of 125 μg/mL, and collagenase showed an inhibition rate of 16.3% at 31.3 μg/mL. The pro-collagen synthesis showed expression of 34%, compared with the negative control when the concentration was 62.5 μg/mL. The antioxidant activity of 250 μg/mL and whitening effect of 62.5 μg/mL are showed in the Results section, and there was no observed deformation or color change even after confirming the stability for 6 months. Even in the human clinical study, the wrinkle improvement before and after using the IBF was 32.2% at maximum, skin melanin and brown spot improvement was 32.5%, pore improvement was 31.5%, and skin density improvement was 12.8%, as shown in the Results section. Conclusion: Therefore, the IBF containing the complex of peptide collagen and naturally derived compounds has a positive effect on wrinkle improvement, skin melanin and brown spot improvement, skin pore improvement, and skin density improvement, as well as exhibiting antioxidant and whitening effects. As a result, IBF can be developed as a key material for cosmetics and foods.

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases. In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.

Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosomal pathway (ALP). Here, we cloned a novel splicing variant of TFEB, comprising 281 amino acids (hereafter referred to as small TFEB), and lacking the helix-loop-helix (HLH) and leucine zipper (LZ) motifs present in the full-length TFEB (TFEB-L). The TFEB variant is widely expressed in several tissues, including the brain, although its expression level is considerably lower than that of TFEB-L. Intriguingly, in cells stably expressing small TFEB, the expression profile of genes was inverted compared to that in cells ectopically expressing TFEB-L. In addition, fisetin-induced luciferase activity of promoter containing either coordinated lysosomal expression and regulation (CLEAR) element or antioxidant response element (ARE) was significantly repressed by co-transfection with small TFEB. Moreover, fisetin-mediated clearance of phosphorylated tau or α-synuclein was attenuated in the presence of small TFEB. Taken together, the results suggest that small TFEB is a novel splicing variant of TFEB that might act as a negative regulator of TFEB-L, thus fine tuning the activity of ALP during cellular stress.

We obtained a new hybrid soybean (Hybrid) by hybridizing β-carotene-enhanced soybean (BCE, Glycine max L.) containing the phytoene synthase-2A-carotene desaturase gene and wild-type soybean (Wild, Glycine soja). To investigate metabolic changes between variants, we performed metabolic profiling of leaves (three growth stages) and seeds. Multivariate analyses revealed significant metabolic differences between genotypes in seeds and leaves, with seeds showing accumulation of phytosterols, tocopherols, and carotenoids (BCE only), indicating co-induction of the methylerythritol 4-phosphate and mevalonic acid pathways. Additionally, Hybrid produced intermediate levels of carotenoids and high levels of amino acids. Principal component analysis revealed metabolic discrimination between growth stages of soybean leaves and identified differences in leaf groups according to different genotypes at 8, 12, and 16 weeks, with Wild showing higher levels of environmental stress-related compounds relative to BCE and Hybrid leaves. The metabolic profiling approach could be a useful tool to identify metabolic links in various soybean cultivars.

Purpose: This study aimed to determine the optimal blending ratio of extracts of Hippophae rhamnoides (H. rhamnoides ) fruit, Rubus fruticosus (R. fruticosus ) leaf, and Perillae folium (P. folium) leaf as a potential functional material for antiwrinkle, antioxidant, anti-inflammatory, and whitening properties. Methods: We used the design of experiment (DOE) efficacy method to identify the optimal blend ratio for a natural extract complex. In addition, we tested the efficacy of the extract complex and the individual extracts by experiments, including elastase inhibition assay, NO inhibition assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay, tyrosinase inhibition assay, and ROS inhibition assay. Results: DOE methods using natural extracts showed that the most efficacious ratio of H. rhamnoides fruit: R. fruticosus leaf: P. folium leaf was 0.25:0.7:0.05. At this ratio, the elastase inhibitory effect, an indicator of wrinkle improvement, was 28% compared to the control. The antioxidant activity was 71.8% higher than the control. Additionally, NO formation was significantly suppressed by the extract complex. Tyrosinase inhibitory activity, a whitening index, showed 24.4% improvement over the control. Finally, hydrogen peroxide-induced cytotoxicity was significantly inhibited following treatment with the extract complex. Conclusion: The natural extract complex of H. rhamnoides , R. Fruticosus , and P. folium was found to have beneficial wrinkle improvement, antioxidant, anti-inflammatory, and whitening effects, and has potential as a functional cosmetic material.

Transcriptional factor EB (TFEB) and nuclear factor E2-related factor 2 (Nrf2) play crucial roles in the biological response against cellular stressors; however, their relationship has not yet been investigated. Here, we constructed human neuroglioma cell lines stably expressing TFEB. The expression of Nrf2-response genes, including heme oxygenase (HO)-1, glutathione-s-transferase-mu1 (GSTM1), and p62, was induced in the cell line, independent of oxidative stress. Of note, the protein level of Nrf2 was significantly increased, and its ubiquitinated fraction was reduced in stable cells compared to that in the control cells. Among E3 ubiquitin ligases known to be involved in the ubiquitination of Nrf2, DDB1 and Cullin4 associated factor 11 (DCAF11) was down-regulated at both protein and mRNA levels in stable cells, indicating that the repression of DCAF11 by TFEB may be mainly involved in the stabilization of Nrf2. In addition, the level of phosphorylated p62 at S349 was highly increased in stable cells compared to that in control cells, which could allow it to interfere with the association of Keap1 and Nrf2, thus stabilizing Nrf2. We suggest for the first time that TFEB could activate Nrf2 by increasing its stability under conditions devoid of oxidative stress.

The use of chemoresistive gas sensors based on metal oxides has expanded to various fields such as medical diagnosis and air quality systems as well as gas leakage detectors with the development of the Internet of Things. Accordingly, sensitivity, selectivity, power consumption, and reproducibility become important factors in the development of gas sensors. Herein, we developed a facile method to fabricate a gas sensor based on porous Au-incorporated tungsten trioxide (WO3) thin films for highly sensitive and selective NO2 sensing. The mixed solution of ammonium tetrathiotungstate [(NH4)2WS4] and gold chloride (AuCl3) was transformed to Au-incorporated WO3 thin films through the spin-coating and annealing process. The gas sensors based on the Au-incorporated WO3 thin films exhibited improved sensitivity, selectivity, and response time upon exposure to NO2 with a significantly low theoretical detection limit of 28 ppt at 150 ℃ compared to gas sensors based on the pristine WO3 thin film. The high sensing properties are attributed to the porous structure and catalytic effects of Au nanoparticles. In addition to these remarkable NO2 sensing properties, the facile and cost-effective fabrication process enlarges the potential of the Au-incorporated WO3 thin films for practical and commercial gas sensing applications.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) such as molybdenum disulfide (MoS2) and tungsten diselenide (WSe2), have recently attracted attention for their applicability as building blocks for fabricating advanced functional materials. In this study, a high quality hybrid material based on 2D TMD nanosheets and ZnO nanopatches was demonstrated. An organic promoter layer was employed for the large-scale growth of the TMD sheet, and atomic layer deposition (ALD) was utilized for the growth of ZnO nanopatches. Photodetectors based on 2D TMD nanosheets and ZnO nanopatches were successfully fabricated and investigated, which showed a high photoresponsivity of 2.7 A/W. Our novel approach is a promising and effective method for the fabrication of photodetectors with a new structure for application in TMD-based transparent and flexible optoelectronic devices.

Residual impurities on the surface of graphene after device fabrication degrade the performance of graphene electronic devices. It is important to solve this issue in order to use graphene in electronic devices. In this study, we removed residues using four plasma treatment methods following the photolithography process. The four plasma treatment methods were hydrogen plasma treatment (Process 1, P1), methane plasma treatment (Process 2, P2), hydrogen plasma pre- and methane plasma post-treatment (Process 3, P3), and hydrogen-methane mixed plasma treatment (Process 4, P4). The results were analyzed using atomic force microscopy and Raman spectroscopy. Of the four treatments, Process 4 showed the most remarkable removal of photoresist residue and healing of the damaged graphene film, thereby improving the mobility of the graphene. The total resistance of the graphene channel in the device was also considerably reduced. These results reveal that a hydrogen-methane mixed plasma treatment (P4) could be a powerful method for removing residue on the surface of graphene after the lithography process.

Curcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.

Aims Berteroin (5-methylthiopentyl isothiocyanate) is a naturally occurring sulforaphane analog containing a non-oxidized sulfur atom in cruciferous vegetables. The objectives of the present study were to determine the effects of berteroin on lipid metabolism in hepatocytes and adipocytes and to elucidate the mechanisms involved. Main methods The effect of berteroin on lipid metabolism were evaluated in liver X receptor α agonist-stimulated HepG2 cells and adipocyte differentiation-induced 3T3-L1 cells using MTT assay, western blot, real time polymerase chain reaction, oil red O staining, and triglyceride assay. Key findings T0901317 treatment increased the expression of sterol regulatory element binding protein (SREBP)-1c, a major transcription factor that mediates lipogenesis, and berteroin pretreatment significantly inhibited the expressions of T0901317-induced SREBP-1c and lipogenic genes. Especially, berteroin had a greater inhibitory effect on T0901317-induced SREBP-1c activation than sulforaphane, AICAR, or metformin. Berteroin also markedly suppressed lipid droplet formations and triglyceride accumulations caused by both T0901317 stimulation in HepG2 hepatocytes and differentiation induction in 3T3-L1 preadipocytes. However, berteroin significantly increased the expression of mitochondrial fatty acid oxidation-related genes (carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptor gamma coactivator-1α) and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in HepG2 cells. Interestingly, effects of berteroin on the expressions of SREBP-1c protein and CPT-1 mRNA were remarkably prevented by compound C (an AMPK inhibitor). Significance Our results suggest berteroin-inhibited hepatic lipid accumulation and adipocyte differentiation might be mediated by AMPK activation and that berteroin might be useful for the prevention, amelioration, and treatment of metabolic diseases, including hepatic steatosis.

For centuries, Fructus ligustri lucidi (FLL, the fruit of Ligustrum lucidum Aiton or Ligustrum japonicum Thunb.) has been commonly used in traditional Chinese medicine for treating hepatitis and aging-related symptoms and in traditional Korean medicine to detoxify kidneys and the liver. Pharmacological research has shown FLL has antioxidant, anti-inflammatory, anticancer, anti-osteoporosis, and hepatoprotective activities. This study was undertaken to investigate the effects of FLL extract (FLLE) on neuroinflammation. After setting a non-toxic concentration using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay data, we investigated the effects of FLLE using Western blotting, cell migration, enzyme-linked immunosorbent assay, a nitric oxide (NO) assay, and immunofluorescence staining in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. FLLE was non-toxic to BV2 cells up to a concentration of 500 μg/mL and concentration-dependently inhibited the production of NO and prostaglandin E2 and the protein levels of inducible nitric oxide synthase and cyclooxygenase-2 under LPS-induced inflammatory conditions. It also inhibited the secretion of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Furthermore, FLLE pretreatment attenuated LPS-induced increases of CD68 (a marker of microglia activation) and suppressed the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-stimulated BV2 cells, and significantly increased heme oxygenase (HO)-1 levels. FLLE also reduced the LPS-induced increase in the migratory ability of BV2 cells and the phosphorylation of vascular endothelial growth factor receptor 1. Collectively, FLLE effectively inhibited inflammatory response by suppressing the MAPK and NF-κB signaling pathways and inducing HO-1 in LPS-stimulated BV2 microglial cells. Our findings provide a scientific basis for further study of FLL as a candidate for preventing or alleviating neuroinflammation.

Objectives. Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. Methods. The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. Results. Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. Conclusions. Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.

An active compound, triterpene saponin, astersaponin I (AKNS-2) was isolated from Aster koraiensis Nakai (AKNS) and the autophagy activation and neuroprotective effect was investigated on in vitro and in vivo Parkinson’s disease (PD) models. The autophagy-regulating effect of AKNS-2 was monitored by analyzing the expression of autophagy-related protein markers in SH-SY5Y cells using Western blot and fluorescent protein quenching assays. The neuroprotection of AKNS-2 was tested by using a 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP+)-induced in vitro PD model in SH-SY5Y cells and an MPTP-induced in vivo PD model in mice. The compound-treated SH-SY5Y cells not only showed enhanced microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and decreased sequestosome 1 (p62) expression but also showed increased phosphorylated extracellular signal–regulated kinases (p-Erk), phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated unc-51-like kinase (p-ULK) and decreased phosphorylated mammalian target of rapamycin (p-mTOR) expression. AKNS-2-activated autophagy could be inhibited by the Erk inhibitor U0126 and by AMPK siRNA. In the MPP+-induced in vitro PD model, AKNS-2 reversed the reduced cell viability and tyrosine hydroxylase (TH) levels and reduced the induced α-synuclein level. In an MPTP-induced in vivo PD model, AKNS-2 improved mice behavioral performance, and it restored dopamine synthesis and TH and α-synuclein expression in mouse brain tissues. Consistently, AKNS-2 also modulated the expressions of autophagy related markers in mouse brain tissue. Thus, AKNS-2 upregulates autophagy by activating the Erk/mTOR and AMPK/mTOR pathways. AKNS-2 exerts its neuroprotective effect through autophagy activation and may serve as a potential candidate for PD therapy.

Purpose Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.Materials and Methods Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.Results A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).Conclusion Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

One of the well‐known strategies for achieving high‐performance light‐activated gas sensors is to design a nanostructure for effective surface responses with its geometric advances. However, no study has gone beyond the benefits of the large surface area and provided fundamental strategies to offer a rational structure for increasing their optical and chemical performances. Here, a new class of UV‐activated sensing nanoarchitecture made of highly periodic 3D TiO2, which facilitates 55 times enhanced light absorption by confining the incident light in the nanostructure, is prepared as an active gas channel. The key parameters, such as the total 3D TiO2 film and thin‐shell thicknesses, are precisely optimized by finite element analysis. Collectively, this fundamental design leads to ultrahigh chemoresistive response to NO2 with a theoretical detection limit of ≈200 ppt. The demonstration of high responses with visible light illumination proposes a future perspective for light‐activated gas sensors based on semiconducting oxides., The high‐performance light‐activated NO2 gas sensors using 3D TiO2 nanostructures are achieved by the unique light harvesting properties of the nanoporous structures. The light scattering effects from optical maze‐like nanostructures and numerous intermediate energy states from atomic layer deposition of the film electronically activate 3D TiO2 and enhance its gas sensing performance under UV illumination.

Background Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. Methods This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. Results Urinary bisphenol A (BLA) level was significantly higher in the DOR group with anti-Müllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). Conclusion BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women., Graphical Abstract

Genetically modified (GM) soybean events CT-4025 and CT-1001, which contain genes encoding thioredoxin and epidermal growth factor, respectively, have previously been developed for use in cosmetic materials. In this study, compositional analyses and metabolic profiling were carried out to assess the unintended effects on the composition of metabolites between GM soybeans and non-GM soybeans. The soybeans were cultivated in 2016 and 2017 in two regions (Ochang and Jeonju) in the Republic of Korea. Statistical analyses were performed using univariate and multivariate methods. Results from the compositional analysis showed that the compositional variation in the tested GM varieties was within the range of conventional varieties. Furthermore, the results of multivariate analysis revealed that the growing year had a much stronger effect on soybean composition than did the growing site or genotypes. In the case of soybeans harvested in 2016, the levels of most amino acids decreased while those of secondary metabolites and sucrose increased, indicating that water stress due to low rainfall in 2016 induced metabolic changes. These results suggest that environmental factors have a major impact on the composition of GM and non-GM soybeans. We further demonstrated that metabolic approaches are useful for investigating the environmental change-induced metabolic network in GM crops intended for use in cosmetic materials.

In this study, a polystyrene-block-polyisoprene-block-polystyrene (SIS) based dielectric paste was fabricated using barium titanate (BT) as dielectric filler in order to produce organic-inorganic composites for 3D dispenser printing applications. Since a high loading of inorganic filler is generally required to obtain high dielectric properties, the surface of BT was modified with two different phosphonic acids having functional groups resembling the groups contained in the block copolymer, in order to achieve a high compatibility between the filler and the polymer matrix. Upon incorporation of 80 wt% of BT in SIS, the dielectric constant was found to be approximately 3 times higher than that of bare SIS. The surface modification of the filler enhanced its dispersion within the polymer matrix, as confirmed by the surface morphology of the composite film at a high filler content. The desired viscoelasticity was achieved through the fine-tuning of the total solid content, and consequently, the potential application of the composite as 3D printable paste was demonstrated through the formation of a layer-by-layer printed structure on a flexible substrate.

Recently, two-dimensional (2D) materials have attracted attention for gas sensor fields due to their unique properties such as high surface to volume ratio and numerous active sites. In particular, reduced graphene oxide (rGO) and MoS2 are one of the most promising materials for humidity sensor due to the oxygen containing functional groups on the surface of rGO and dangling bonds at the edge site of MoS2. Herein, we present 2D rGO/2D MoS2 hybrid composites (MS-GOs) synthesized by hydrothermal method. rGO and MoS2 are mixed with different molar ratios and drop-casted on SiO2 substrate with Pt interdigitated electrode. At an optimized molar ratio of rGO/MoS2, the sensor device exhibits high sensitivity, good selectivity, rapid response and recovery, and good linearity for humidity sensing. The enhanced sensing properties are attributed to the p-n junction between rGO and MoS2. Our work provides an efficient way for realizing high-performance and fast responding humidity sensors utilizing 2D-2D heterojunction materials based chemoresistive humidity sensors for use in diverse applications.

Reduced graphene oxide (rGO) and MoS2, the most representative two-dimensional (2D) materials, are receiving significant attention for the fabrication of sensing devices owing to their high surface area, many abundant sites, and excellent mechanical flexibility. Herein, we demonstrated chemoresistive humidity sensors with fast response, excellent selectivity, and ultrahigh sensitivity based on 2D rGO and 2D MoS2 hybrid composites (RGMSs). The RGMSs were fabricated by simple ultrasonication without the addition of additives and additional heating. Compared to pristine rGO, the RGMS exhibited a 200 times higher response to humidity at room temperature. The significant enhancement in the sensing performance of the composite was attributed to electronic sensitization due to p–n heterojunction formation and porous structures between rGO and MoS2. The synergistic combination of rGO and MoS2 could be applied to construct a flexible humidity sensor. The sensing performance of an RGMS flexible device remains the same before and after bending; this indicates that the use of rGO and MoS2 is a viable new and simple strategy to realize a humidity sensor for use in wearable electronics.

Lipophilic bioactive compounds and hydrophilic primary metabolites from potato (solanum tubersum L.) tubers with different-colored flesh (white-, yellow-, red-, and purple) were characterized. The carotenoid content was relatively higher in red-colored potatoes, in which lutein was most plentiful. Among the other lipophilic compounds analyzed, including policosanols, tocopherols, and phytosterols, octacosanol was measured in the largest amount, followed by β-sitosterol, irrespective of color variations. Forty-three hydrophilics consisting of amino acids, organic acids, sugars, and sugar alcohols and 18 lipophilics were subjected to data-mining processes. The results of multivariate statistical analyses clearly distincted the different varieties and separated red-fleshed potatoes from other color-fleshed potatoes according to abundance of amino acids, sugars, and carotenoids. This study confirmed the metabolic association-related biochemical pathway between metabolite characteristic and color differences in potato tubers. These results can facilitate understanding the metabolic differences among diverse colored potatoes and provide fruitful information for genetic engineering of potato cultivars.

Liquid viscosity is an important physical property utilized in engineering designs for transportation and processing of fluids. However, the measurement of liquid viscosity is not always easy when the materials have toxicity and instability. In this study, a modified scaled variable reduced coordinate (SVRC)-quantitative structure property relationship (QSPR) model is suggested and analyzed in terms of its performance of prediction for liquid viscosity compared to the conventional SVRC-QSPR model and the other methods. The modification was conducted by changing the initial point from triple point to ambient temperature (293 K), and assuming that the liquid viscosity at critical temperature is 0 cP. The results reveal that the prediction performance of the modified SVRC-QSPR model is comparable to the other methods as showing 7.90% of mean absolute percentage error (MAPE) and 0.9838 of R 2. In terms of both the number of components and the performance of prediction, the modified SVRC-QSPR model is superior to the conventional SVRC-QSPR model. Also, the applicability of the model is improved since the condition of the end points of the modified model is not so restrictive as the conventional SVRC-QSPR model.

Nutritional composition is important for assessing the safety of genetically modified (GM) crops for human consumption. Three beta-carotene-enhanced soybean lines were developed by introducing the β-conglycinin promoter::Phytoene synthase-2A-Carotene desaturase/t35S gene cassette into the genome of the commercial Kwangan (Glycine max L.) soybean variety. Transgenic soybeans were successfully detected on beta-carotene productions ranged from 170.47 to 213.58 µg/g. Comparative assessments of nutrition were conducted with 3 transgenic soybeans, their non-GM counterpart, and several commercial soybean varieties. Results indicated that most levels of proximate, fatty acids, amino acids, and vitamins showed non-significant differences between transgenic soybeans and their counterpart, and fit within the reference ranges established for other commercial soybeans and Organization for Economic Cooperation and Development Guidelines. However, significant differences on levels of crude fat, carbohydrate, δ-tocopherol, and oleic acid of transgenic soybeans comparing to those of non-transgenic counterpart Kwangan cannot eliminate the influences of transgene insertion. Alternations on compositions should be definite by further studies, such as transcriptome and metabolome profiling.

Tar formation resulting during lignocellulosic biomass gasification is a major impediment to utilizing biomass energy sources, in that it blocks and fouls the processing equipment; as such, any tar present in the produced syngas much be effectively removed. This study analyzes the ability of commercially available Ni and Ru based CH4 reforming catalysts to effect tar removal and compares deactivation characteristics. Toluene was used as the model biomass tar at concentrations of 30 and 100 g/Nm3. Several additional parameters were also tested, including reaction temperatures (400–800 °C), space velocities (5000–30,000 h−1), and the steam/toluene ratios (2–20). The variation of toluene conversion and product gas composition with reaction conditions was analyzed. Overall, H2 and CO production were favored by the Ru catalyst and generally increased with temperature. Conversion also increased with temperature, with conversions higher than 90% obtained at 800 °C.

A cross-stacking MoS2/graphene hybrid patterns for the application to advanced flexible opto-electronic devices have been demonstrated by soft-lithographic patterning method. Well-defined MoS2/graphene hybrid pattern was fabricated simply by a soft lithographic patterning technique. In-depth exploration for the optical properties of diverse cross-stacking photodetectors based on MoS2/graphene patterns was carried out. In addition, cross-stacking MoS2/graphene was demonstrated onto a flexible polyethylene terephthalate (PET) substrate for the analysis of physical properties of devices. Substantially, this method should pave the way for realistic applications of transparent and flexible nano-electronic devices based on 2D materials.

Kohlrabi (Brassica oleracea var. gongylodes) is a dietary Brassica vegetable with noted health-beneficial properties associated with its numerous metabolites. The aim of this study was to elucidate phenotypic variation between the two cultivars through comprehensive analysis of the relationship of their primary and secondary metabolites. High-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS) are considered useful tools for profiling primary and secondary metabolites. A total of 45 metabolites, including organic acids, amino acids, sugars, and an amine, were identified in pale green and purple kohlrabies using GC-TOFMS-based metabolic profiling. The resulting data sets were analyzed by principal component analysis to determine the overall variation, and the purple and pale green vegetables were separated by the score plots generated. Additionally, HPLC analysis of anthocyanins in both cultivars revealed that green kohlrabies did not contain any anthocyanidins, while 11 anthocyanins were quantified in the purple ones. Cyanidin was the dominant anthocyanin found in the purple cultivar, with cyanidin-3-(feruloyl)-diglucoside-5-glucoside being the major one. This study suggests that GC-TOFMS and HPLC are suitable tools to determine metabolic connection among various metabolites and describe phenotypic variation between green and purple kohlrabies.

Vitamins are known to be associated with immunity and nutrition. Moreover, vitamin deficiency can affect host immunity to various infectious diseases, including tuberculosis. Although patients with tuberculosis often have vitamin D deficiency, little is known about the levels of other vitamins. Here, we aimed to investigate the status of vitamins A, BWe performed a case-control study to investigate the serum vitamin concentrations in 152 patients with tuberculosis and 137 control subjects. The concentrations of vitamin A, vitamin D, vitamin E, homocysteine, and methylmalonic acid were measured using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. Patient demographic data and other biochemical parameters were also analyzed.The serum concentrations of vitamins A, D, and E were significantly lower in patients with tuberculosis than in control subjects (1.4 vs. 2.0 μmol/L, P 0.001; 10.6 vs. 19.3 ng/mL, P 0.001; and 22.8 vs. 30.6 μmol/L, P 0.001, respectively). In contrast, the methylmalonic acid levels were higher in patients with tuberculosis (134.9 vs. 110.8 nmol/L, P 0.001). The prevalences of vitamin deficiencies were significantly higher in patients with tuberculosis. Moreover, multiple vitamin deficiencies were only observed in patients with tuberculosis (22.4% of all patients with tuberculosis vs. 0% of all control subjects). Positive correlations among vitamin A, D, and E concentrations were observed (vitamins A and D, r = 0.395; vitamins D and E, r = 0.342; and vitamins A and E, r = 0.427, P 0.001). Body mass index, total cholesterol, low-density lipoprotein, iron, and total iron-binding capacity all showed positive correlations with vitamin A, D, and E concentrations.Vitamin deficiencies are common in patients with tuberculosis. Further research investigating the clinical importance of vitamin and nutritional status in patients with tuberculosis is needed.

Chemoresistive gas sensors based on two-dimensional (2D) materials including graphene-based materials have attracted significant research interest owing to their potential use in next-generation technologies including the Internet of Things (IoT). The functionalization of 2D materials is considered as a key strategy to achieve superior gas sensing properties such as high selectivity, high sensitivity, and reversible response and recovery, because it can modulate the chemical and electrical properties of 2D materials for more efficient gas sensing. Herein, we present a facile solution process and the room temperature gas sensing properties of chemically fluorinated graphene oxide (CFGO). The CFGO sensors exhibit improved sensitivity, selectivity, and reversibility upon exposure to NH3 with a significantly low theoretical detection limit of ∼6 ppb at room temperature in comparison to NO2 sensing properties. The effect of fluorine doping on the sensing mechanism is examined by first-principles calculations based on density functional theory. The calculations reveal that the fluorine dopant changes the charge distribution on the oxygen containing functional groups in graphene oxide, resulting in the preferred selective adsorption and desorption of NH3 molecules. We believe that the remarkable NH3 sensing properties of CFGO and investigation by first-principles calculations would enlarge the possibility of functionalized 2D materials for practical gas sensing applications such as the IoT.

Background: Normal cells are sensitive to anoikis, which is a cell detachment-induced apoptosis. However, cancer cells acquire anoikis resistance that is essential for successful metastasis. This study aimed to demonstrate the function and potential mechanism of NADPH oxidase 4 (NOX4) and EGFR activation in regulating anoikis resistance in lung cancer. Methods: Cells were cultured either in the attached or suspended condition. Cell viability was measured by cell counting and live and dead cell staining. Expression levels of NOX4 and EGFR were measured by PCR and immunoblotting. Reactive oxygen species (ROS) levels were measured by flow cytometry. Effects of NOX4 overexpression or NOX4 knockdown by si-NOX4 on anoikis sensitivity were explored. Levels of NOX4 and EGFR in lung cancer tissues were evaluated by IHC staining. Results: NOX4 was upregulated but EGFR decreased in suspended cells compared with attached cells. Accordingly, ROS levels were increased in suspended cells, resulting in the activation of Src and EGFR. NOX4 knockdown decreased activation of Src and EGFR, and thus sensitised cells to anoikis. NOX4 overexpression increased EGFR levels and attenuated anoikis. NOX4 expression is upregulated and is positively correlated with EGFR levels in the lung cancer patient tissues. Conclusions: NOX4 upregulation confers anoikis resistance by ROS-mediated activation of EGFR and Src, and by maintaining EGFR levels, which is critical for cell survival.

Oxidative stress causes neuronal cell death in various neurodegenerative diseases, such as Alzheimer’s disease, ischemia, and Parkinson’s disease. Therefore, reducing intracellular reactive oxygen species (ROS) has been evaluated as an effective treatment strategy for neurodegenerative disorders. Methyl lucidone (MLC) extracted fromLindera erythrocarpaMakino (Lauraceae) has been previously reported to exhibit microglial-mediated neuroprotective effects via inhibiting neuroinflammation. However, the antioxidant effects of MLC are still unclear. The aim of this study was to determine the neuroprotective mechanism of MLC in HT-22 neurons against oxidative stress induced by glutamate. In results, the pretreatment of MLC significantly enhanced the viability of HT-22 cells under glutamate-induced oxidative conditions, suggesting that MLC has a neuronal mechanism to protect neurons without microglial regulation. Also, the glutamate effect to increase ROS production was effectively blocked by MLC without any free radical scavenging activity. To induce this antioxidant effect, MLC upregulated the expression of heme oxygenase 1 (HO-1) and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf-2), known as an intracellular antioxidant enzyme, and its transcription factor. Additionally, Akt phosphorylation regulating Nrf-2 was confirmed to be involved in the neuroprotective signaling activated by MLC. These results indicate that MLC may play a role as an antioxidant agent to inhibit neurodegenerative processes via activating antioxidant signaling pathways that include Nrf-2 and phosphatidylinositol 3-kinase (PI3K).

ObjectiveTo assess the effect of vitamin D and calcium supplementation in preventing recurrences of benign paroxysmal positional vertigo (BPPV).MethodsWe performed an investigator-initiated, blinded-outcome assessor, parallel, multicenter, randomized controlled trial in 8 hospitals between December 2013 and May 2017. Patients with confirmed BPPV were randomly assigned to the intervention (n = 518) or the observation (n = 532) group after successful treatment with canalith repositioning maneuvers. The primary outcome was the annual recurrence rate (ARR). Patients in the intervention group had taken vitamin D 400 IU and 500 mg of calcium carbonate twice a day for 1 year when serum vitamin D level was lower than 20 ng/mL. Patients in the observation group were assigned to follow-ups without further vitamin D evaluation or supplementation.ResultsThe intervention group showed a reduction in the ARR (0.83 [95% confidence interval (CI), 0.74–0.92] vs 1.10 [95% CI, 1.00–1.19] recurrences per 1 person-year) with an incidence rate ratio of 0.76 (95% CI, 0.66–0.87, p < 0.001) and an absolute rate ratio of −0.27 (−0.40 to −0.14) from intention-to-treat analysis. The number needed to treat was 3.70 (95% CI, 2.50–7.14). The proportion of patients with recurrence was also lower in the intervention than in the observation group (37.8 vs 46.7%, p = 0.005).ConclusionsSupplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal.Classification of evidenceThis study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV.

Red peppers are a remarkable source of nutrients in the human diet. However, comprehensive studies have not reported on the effects of genotype, cultivation region, and year on pepper fruit characteristics. To address this, 12 commercial pepper varieties were grown at two locations in South Korea, during 2016 and 2017, representing four environments, and concentrations of proximate, minerals, amino acids, fatty acids, capsaicinoids, and free sugars in pepper pericarps were determined. Variation in most nutrients was observed among the 12 varieties grown within each location in each year, indicating a significant genotype effect. Statistical analysis of combined data showed significant differences among varieties, locations, and years for the measured components. The % variability analysis demonstrated that environment (location and year) and genotype-environment interaction contributed more to the nutritional contents than genotype alone. Particularly, variation in many amino acids, capsaicinoids, free sugars, and myristic acid was attributed to location. Year effect was significant for palmitoleic acid, ash, tryptophan, copper, linolenic acid, crude fiber, and tyrosine. Insoluble dietary fiber, soluble dietary fiber, sodium, sulfate, linoleic acid, and alanine were primarily varied by genotype–environment interaction. Palmitic acid was the trait the most highly affected by genotype. Cultivation and the genotype–environment interaction have a major role in determining the composition of 12 pepper varieties across four environments. The data from this study could explain the natural variation in the compositional data of peppers by genotypes and environments.

Graphene is one of the most promising materials for high-performance gas sensors due to its unique properties such as high sensitivity at room temperature, transparency, and flexibility. However, the low selectivity and irreversible behavior of graphene-based gas sensors are major problems. Here, we present unprecedented room temperature hydrogen detection by Au nanoclusters supported on self-activated graphene. Compared to pristine graphene sensors, the Au-decorated graphene sensors exhibit highly improved gas-sensing properties upon exposure to various gases. In particular, an unexpected substantial enhancement in H2 detection is found, which has never been reported for Au decoration on any type of chemoresistive material. Density functional theory calculations reveal that Au nanoclusters on graphene contribute to the adsorption of H atoms, whereas the surfaces of Au and graphene do not bind with H atoms individually. The discovery of such a new functionality in the existing material platform holds the key to diverse research areas based on metal nanocluster/graphene heterostructures.

Although transition metal carbides (TMCs) exhibit intriguing physical and chemical properties, a central issue for multifaceted applications based on TMC materials is to meet a large-scale and reliable synthetic route of air-stable TMC materials. Here, the primary aim is to address the issues by synthesizing Mo2C encapsulated with multilayer graphene coral-like nanostructure. The oxidation stability of Mo2C can be effectively compensated by the complementary hybridization of multilayer graphene, which serves as a perfect chemical barrier. Large-scale graphene/Mo2C can be readily synthesized on commercial Mo foils by surface-oxidation-mediated chemical vapor deposition. Explicit structural and chemical evaluation was implemented to explore the structural and chemical manipulation of Mo2C by selecting the starting material (Mo or MoO3). Differences in the thickness of the oxide layers on the Mo surface led to structural and material diversities for the formation of Mo2C with nanogranular and graphene/Mo2C coral-like nanostructures. The capability of graphene/Mo2C for applications in nanostructured electrodes and heaters was validated by its extraordinary electrical conductivity, substantial enhancement in chemical durability and mechanical flexibility, and outstanding performance of deformable heaters.