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Since the first demonstration of a biosensor was reported, big efforts have been reported to improve the sensing performance of bioelectronics by investigating the material compositions, device configurations, process optimization, and system integration. In this paper, we demonstrate highly sensitive wearable carbon-based glucose sensors fabricated by all-solution process at low temperature. Solution-processed single-wall carbon nanotube (SWCNT) random networks as a sensing platform were surface-functionalized with the enzyme glucose oxidase (GOD)-nafion composites, which can detect glucose down to 50 μM with a response time of less than 5 s. We also investigate the sensing mechanism of SWCNT-based glucose sensors through molecular oxidation-reduction reactions in GOD with glucose. Material characterization using X-ray photoelectron spectroscopy and Raman spectra measurements proves the existence of SWCNT random networks with chemical incorporation through a surface-functionalization process. We believe that the proposed wearable SWCNT-based glucose sensors fabricated by all-solution process can open up a promising route to realize a low-cost and high performance health-care diagnosis system integrated with the user’s smartphone for diabetic patients.

Cinnamomum cassia has been widely used as a natural product to treat diseases in Asia due to its diverse pharmacological functions including anti-inflammatory, anti-oxidant, anti-microbial, anti-diabetic, and anti-tumor effects. Despite its ethnomedicinal benefits, little information regarding its toxicity is currently available. The aim of this study was to evaluate its potential long-term toxicity and genotoxicity in compliance with test guidelines of the Organization for Economic Cooperation and Development. A 13-week repeat-dose oral toxicity study revealed that body weights of rats were normal after receiving cinnamon extract at up to 2000 mg/kg. High-dose intake of cinnamon extract (2000 mg/kg) showed potential nephrotoxicity and hepatotoxicity to both males and females as evidenced by obvious increases of kidney/liver weight along with a small but statistically elevation of total cholesterol level. Overall findings from genetic toxicity testing battery including Ames test, in vitro mammalian cell micronucleus assay, and in vivo bone marrow micronucleus assay indicated that cinnamon extract was not mutagenic or clastogenic. In conclusion, cinnamon extract may possess potential nephrotoxicity and hepatotoxicity at dose higher than its recommended daily safe dose. Further study is needed to clarify the mechanism involved in its induction of liver and kidney injury.

Wearable triboelectric nanogenerators (TENGs) are considered viable for mobile applications of self-powered electronics operating on human body but limited by relatively low output performance. In this study, the effects of interfacial layers used as hole transport layers (HTLs) which affect triboelectric charge separation on the output performance of TENGs are investigated. Comparative analyses of different interfacial layers prove that the incorporation of single-wall carbon nanotube (SWCNT) random networks into TENGs can reduce the loss of triboelectric charges. Improvements in the charge-repelling force and hole-blocking barrier at the interface between the HTL and electrode enabled the wearable TENGs to achieve output voltages of ∼760 V and currents of ∼51 μA at 3 Hz. Such advances can be realized by optimizing SWCNT-based HTL through a simple and effective bar-printing technology in an ambient atmosphere. Moreover, a practical application of the wearable TENG exhibiting a maximum instantaneous power of 19.2 mW and a power density of 0.77 mWcm−2 with a load resistance of 5 MΩ is demonstrated. Mechanical finger-tapping on wearable TENGs enables operation of small electric devices without energy storage. The utilization of SWCNT-based HTLs fabricated by effective and practical bar-printing can stimulate the development of energy-harvesting technologies based on wearable TENGs.

Although conventional skin-attachable electronics exhibit good functionalities, their direct attachment (without any adhesive) to human skin with sufficient conformal contact is challenging. Herein, all-solution-processed on-skin electronics based on self-reconfigurable high-weight-per- volume-gelatin (HWVG) film constructed using an effective, biocompatible water absorption-evaporation technique are demonstrated. Completely conformal contact of self-reconfigurable HWVG films is realized by rapidly inducing anisotropic swelling in the perpendicular direction and covering any curvature on the skin without spatial gap or void after shrinking. A sufficiently thin HWVG film (~2 um) exhibited higher adhesion owing to van der Waals force and the carboxylic acid and amine groups in HWVG film form cross-linkages through intermolecular bonds with human skin. Self-reconfigurable HWVG films with high biocompatibility are optimized to afford a superior efficiency of 87.83 % at a concentration of 20 % (w/v) and a storage modulus of 1822 MPa at 36.5 °C. Furthermore, functional nanoelectrodes consisting of self-reconfigurable silver nanowires/HWVG films for high-performance on-skin sensors allowing the detection of sensitive motion and electrophysiological signals, as well as an armband-type sensor system incorporated with a smartphone for health-care monitoring are demonstrated. Outstanding performances, including stability, reliability, flexibility, re-usability, biocompatibility, and permeability of on-skin electronics based on HWVG films can open-up a prospective route to realizing breathable human-machine interfaces based on biocompatible materials and processes.

Artemisia capillaris (AC) has been used as an alternative therapy in obesity, atopic dermatitis, and liver diseases through several biological activity including anti-steatotic, antioxidant, and anti-inflammatory activities. Despite its ethnomedicinal benefits, no sufficient background information is available about the long-term safety and genotoxicity of the AC extract. Therefore, the present study was carried out to investigate the 13-week subchronic toxicity and genotoxicity of the AC extract according to the test guidelines published by the Organization for Economic Cooperation and Development. In the 13-week toxicity study using doses of 25, 74, 222, 667, and 2000 mg/kg body weight, oral administration of the AC extract in male and female rats did not result in any significant adverse effects in food/water consumption, body weight, mortality, hematology, serum biochemistry, organ weight and histopathology. Accordingly, the no-observed-adverse-effect level in rats of both genders was established for the AC extract at 2000 mg/kg/day, the highest dose level tested. In addition, the AC extract was not genotoxic in a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. In conclusion, we demonstrated that the AC extract is considered as a safe traditional medicine for human consumption.

In vivo animal studies are required by regulatory agencies to investigate drug safety before clinical trials. In this review, we summarize the process of selecting a relevant non-rodent species for preclinical studies. The dog is the primary, default non-rodent used in toxicology studies with multiple scientific advantages, including adequate background data and availability. Rabbit has many regulatory advantages as the first non-rodent for the evaluation of reproductive and developmental as well as local toxicity. Recently, minipigs have increasingly replaced dogs and rabbits in toxicology studies due to ethical and scientific advantages including similarity to humans and breeding habits. When these species are not relevant, nonhuman primates (NHPs) can be used as the available animal models, especially in toxicology studies investigating biotherapeutics. Particularly, based on the phylogenetic relationships, the use of New-World marmosets can be considered before Old-World monkeys, especially cynomolgus with robust historical data. Importantly, the use of NHPs should be justified in terms of scientific benefits considering target affinity, expression pattern, and pharmacological cross-reactivity. Strict standards are required for the use of animals. Therefore, this review is helpful for the selection of appropriate non-rodent in regulatory toxicology studies by providing sufficient regulatory, ethical, and scientific data for each species.

High-performance flexible pH sensors based on nanocomposites of single-wall carbon nanotubes (SWCNTs) and Nafion, fabricated by screen printing on flexible substrates in ambient air are demonstrated. The electrical characteristics and thus the sensing performance of the pH sensors monitoring the change in resistance of printed nanocomposite films in a wide range of pH from 1 to 12 were controlled by the number of printed layers in multi-patterns. The operational stability of the flexible pH sensors was nearly unchanged after 200 cycles of bending tests having a curvature radius of 5 mm, which is essential for intergration of flexible pH sensors into wearable nanoelectronics. The sensing mechanism of the chemiresistive pH sensors based on nanocomposites is investigated in terms of chemical reaction. The hydrogen or hydroxide ions in the pH solution interact with the carbonyl and C H bonds bonds of the nanocomposite film, which induces or withdraws positively charged carriers, respectively. In addition, a real-time pH sensor system integrated into a drone application with wireless communication and data transmitting modules is demonstrated for the simultaneous visualization of processed data and remote detection of targets on the user's smartphone based on a designed Android algorithm.

The functional inhibition of mast cells, which serve as a key effector cells in allergic reactions may be a specific target for treating immunoglobulin (Ig)E-mediated allergic reactions, which occur in various allergic diseases including anaphylaxis, asthma, and atopic dermatitis. In this study, we demonstrated the effects of dabrafenib, a therapeutic agent used to treat metastatic melanoma, with a focus on mast cell activation and local cutaneous anaphylaxis. In two types of mast cells (RBL-2H3 and mouse bone marrow-derived mast cells), dabrafenib (0.01, 0.1, 1 μM) pretreatment significantly decreased IgE-induced degranulation, intracellular calcium influx, and the activity of intracellular signaling molecules, such as Lyn, Syk, Akt, and PLCγ. Dabrafenib ameliorated mRNA and protein expression levels of interleukin-4 and tumor necrosis factor-α by the reduction of nuclear localization of nuclear factor-κB and nuclear factor of activated T-cells. In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10 mg/kg) reduced local pigmentation and ear thickness in a dose-dependent manner. Taken together, these results suggest that dabrafenib is a therapeutic drug candidate that controls IgE-mediated allergic inflammatory diseases through suppression of mast cell activity.

Although many methods to assess sensitization have been investigated to replace animal testing, it is still imperative to develop an in vitro method to minimize the use of animals and to classify sensitizers. Recently, an assay using the human keratinocyte cell line (HaCaT) was developed as an alternative method. Our aim was to optimize this method and validate its ability to assess sensitization. The highest dose that resulted in 75% cell viability was determined for each test substance. Then, serial dilutions of the dose were applied to measure the levels of secreted proinflammatory cytokines. To optimize the assay, statistical analyses were performed to determine whether all of the doses tested were necessary to maintain the predictive values. Exclusion of the 0.5× dose did not change the predictive values drastically. To validate the optimized method, 22 substances were evaluated without the 0.5× dose, resulting in overall predictive values of 83.3% for sensitivity, 80.0% for specificity, and 81.8% for accuracy, which are comparable to results from other validated assays. These results suggest that statistical analysis can assist in development of alternative in vitro methods and that the optimized HaCaT cell assay is reproducible.

As a well-known traditional medicine, Angelica gigas (AG) and its active constituents, including decursin and decursinol, have been shown to possess several health beneficial properties such as anti-bacterial, immunostimulating, anti-tumor, neuroprotective, anti-nociceptive and anti-amnestic activities. However, there is lack of toxicity studies to assess potential toxicological concerns, especially long-term toxicity and genotoxicity, regarding the AG extract. Therefore, the safety of AG extract was assessed in subchronic toxicity and genotoxicity assays in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In a subchronic toxicity study for 13 weeks (125, 250, 500, 1000 and 2000 mg/kg body weight, delivered by gavage), data revealed no significant adverse effects of the AG extract in food consumption, body weight, mortality, hematology, biochemistry, necropsy, organ weight and histopathology throughout the study in male and female rats. These results suggest that no observed adverse effect level of the AG extract administered orally was determined to be greater than 2000 mg/kg/day, the highest dose tested. In addition, a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay suggested that the AG extract was not genotoxic. In conclusion, the AG extract appears to be safe as a traditional medicine for oral consumption.

Paecilomyces tenuipes is entomogenous fungus that is called snow-flake Dongchunghacho in Korea. Although it is widely used in traditional medicines, its safety has not yet been comprehensively investigated. Therefore, the aim of this study was to evaluate the genotoxicity, acute and subchronic toxicity of P. tenuipes . The acute oral LD 50 of P. tenuipes extract in rats was estimated to be greater than 2000 mg/kg of body weight. In the subchronic study, the oral treatment of rats with 500, 1000 or 2000 mg/kg P. tenuipes extract daily for 13 weeks did not induce any dose-related changes (body weight, food consumption, clinical observation, urinalysis, hematology, clinical chemistry and organ weight). In contrast, histopathological observation revealed that P. tenuipes extract induced karyomegaly in outer medulla of kidney in all treated rats. Importantly, P. tenuipes extract exerted the mutagenic potential in Ames assay. Since karyomegalic alterations have been known to be associated with carcinogenicity, our finding on the mutagenicity of P. tenuipes extract supports the possibility on the potential involvement of P. tenuipes in carcinogenicity at least partially. In conclusion, the subchronic oral exposure of P. tenuipes may induce kidney abnormality at the concentration higher than 500 mg/kg body weight, although further studies using other animal models are needed to identify the toxicity of P. tenuipes .

We demonstrate human-interactive drone remote control system consisting of high-performance printed strain/pressure sensors with carbon-based nanocomposites, fabricated by all-solution-process at 80 °C. The armband-type drone remote control system was designed by a main control operation module, a sensing module and a signal processing module at an overall size of 12 cm × 7 cm x 1.5 cm (width x length x height). Rapid and accurate sensing properties of the sensing module were realized by the structural integration of nanocomposites on flexible/stretchable substrates attached to the human body. Furthermore, simultaneous visualization of processed data on the user's smartphone with an Android application by detecting the movements of human-body in real-time can open up new routes for the upcoming internet of things platform based on nanocomposition in industries. Notably, it is the feasible demonstration of a system-level drone remote controller operated by signal processing in real-time from highly sensitive printed strain/pressure sensors with carbon-based nanocomposites, exhibiting important functionality of waterproof and electric-isolation for human-interactive electronics.

Ethnopharmacology relevance Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. Aim of the study Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. Materials and methods We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. Results Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. Conclusion The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine.

The size effect of nanomaterials is of major interest, since it may affect their bioavailability and toxicity. In this study, bovine serum albumin (BSA) nanoparticles were prepared using a modified desolvation method. Bare BSA nanoparticles and calcium (Ca)-loaded BSA nanoparticles were fabricated at the targeted sizes, 100, 400, and 800 nm. The mean diameters of the prepared BSA nanoparticles were 125, 393, and 713 nm; those of the Ca-BSA nanoparticles were 260, 353, and 919 nm. The surface-area-to-volume-ratios of the prepared BSA nanoparticles were 4.82, 1.53, and 1.03 nm −1 ; those of the Ca-BSA nanoparticles were 2.34, 1.72, and 0.90 nm −1 . The size and the surface-area-to-volume-ratio of the BSA nanoparticles were controlled by adjusting BSA concentration, pH, and NaCl content, which affected the coagulation of the BSA molecules. The surface-area-to-volume-ratio is a more useful parameter than the mean diameter of particles for comparing effectiveness of nanoparticles.