Homemade weaning foods as a source of lead and mercury exposure in Korean infants - A dietary risk assessment study.

Lead (Pb) and mercury (Hg) are neurodevelopmental toxicants that pose risks to cognitive and behavioral health. Given early childhood's vulnerability to these metals, understanding their sources and pathways of exposure during infancy is crucial for public health. During the weaning process, infants may be exposed to metals through the baby food they consume. We aimed to assess metal exposure through homemade weaning foods by analyzing 288 samples consumed by 157 Korean infants aged 6-, 9-, 12-, 15-, and 24-27 months. Pb was detected in 65 % of samples, with levels reaching up to 169 ng/g. Notably, 58 % exceeded the Maximum Level (ML) of 10 ng/g, with a median concentration of 14.7 ng/g fresh weight. Total Hg was found in 88 % of samples, with a median concentration of 4.56 ng/g fresh weight. Estimated median daily intakes of Pb and Hg were 0.29 and 0.09 µg/kg/d, respectively. Considering a benchmark dose for Pb (0.5 µg/kg/d by EFSA), 94 % (the margin of exposure <10) of all age groups was estimated to have a potential health concern associated with homemade baby food consumption. For Hg, only 6 % exceeded a hazard quotients of 1 compared to a provisional tolerable weekly intake for Hg (4 µg/kg/week by WHO). This study marks the first direct assessment of daily Pb and Hg intake through homemade baby food among Korean infants. Our findings underscore the urgent need for heightened awareness regarding metal exposure through homemade baby food.

Exploring the Category and Use Cases on Digital Therapeutic Methodologies.

OBJECTIVES: As the Fourth Industrial Revolution advances, there is a growing interest in digital technology. In particular, the use of digital therapeutics (DTx) in healthcare is anticipated to reduce medical expenses. However, analytical research on DTx is still insufficient to fuel momentum for future DTx development. The purpose of this article is to analyze representative cases of different types of DTx from around the world and to propose a classification system. METHODS: In this exploratory study examining DTx interaction types and representative cases, we conducted a literature review and selected seven interaction types that were utilized in a large number of cases. Then, we evaluated the specific characteristics of each DTx mechanism by reviewing the relevant literature, analyzing their indications and treatment components. A representative case for each mechanism was provided. RESULTS: Cognitive behavioral therapy, distraction therapy, graded exposure therapy, reminiscence therapy, art therapy, therapeutic exercise, and gamification are the seven categories of DTx interaction types. Illustrative examples of each variety are provided. CONCLUSIONS: Efforts from both the government and private sector are crucial for success, as standardization can decrease both the expense and the time required for government-led DTx development. The private sector should partner with medical facilities to stimulate potential demand, carry out clinical research, and produce scholarly evidence.

Three-dimensional microengineered vascularised endometrium-on-a-chip.

STUDY QUESTION: Can we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model? SUMMARY ANSWER: Our representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner. WHAT IS KNOWN ALREADY: Organ-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems. STUDY DESIGN, SIZE, DURATION: The device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost. Two central channels are for 3D culture and morphogenesis of stromal fibroblast and endothelial cells. In addition, the outermost channel is for the culture of additional endometrial stromal fibroblasts that secrete biochemical cues to induce directional pro-angiogenic responses of endothelial cells. To seed endometrial epithelial cells, on Day 8, Ishikawa cells were introduced to one of the two medium channels to adhere on the gel surface. After that, the microengineered endometrium was cultured for an additional 5-6 days (total ∼ 14 days) for the purpose of each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Microfluidic 3D cultures were maintained in endothelial growth Medium 2 with or without oestradiol and progesterone. Some cultures additionally received exogenous pro-angiogenic factors. For the three distinct layers of microengineered endometrium-on-a-chip, the epithelium, stroma and blood vessel characteristics and drug response of each distinct layer in the microfluidic model were assessed morphologically and biochemically. The quantitative measurement of endometrial drug delivery was evaluated by the permeability coefficients. MAIN RESULTS AND THE ROLE OF CHANCE: We established microengineered vascularised endometrium-on-chip, which consists of three distinct layers: epithelium, stroma and blood vessels. Our endometrium model faithfully recapitulates in-vivo endometrial vasculo-angiogenesis and hormonal responses displaying key features of the proliferative and secretory phases of the menstrual cycle. Furthermore, the effect of the emergency contraception drug levonorgestrel was evaluated in our model demonstrating increased endometrial permeability and blood vessel regression in a dose-dependent manner. We finally provided a proof of concept of the multi-layered endometrium model for embryo implantation, which aids a better understanding of the molecular and cellular mechanisms underlying this process. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This report is largely an in-vitro study and it would be beneficial to validate our findings using human primary endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS: Our 3D microengineered vascularised endometrium-on-a-chip provides a new in-vitro approach to drug screening and drug discovery by mimicking the complicated behaviours of human endometrium. Thus, we suggest our model as a tool for addressing critical challenges and unsolved problems in female diseases, such as endometriosis, uterine cancer and female infertility, in a personalised manner. STUDY FUNDING/COMPETING INTEREST(S): This work is supported by funding from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) to Y.J.K. (No. 2018R1C1B6003), to J.A. (No. 2020R1I1A1A01074136) and to H.S.K. (No. 2020R1C1C100787212). The authors report no conflicts of interest.

Hyperthermic intraperitoneal chemotherapy as consolidation treatment of advanced stage ovarian cancer.

OBJECTIVE: To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. METHODS: A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. RESULTS: The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. CONCLUSION: This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.

CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice.

Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin ß3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

Self-Healable Organic Electrochemical Transistor with High Transconductance, Fast Response, and Long-Term Stability.

The major challenges in developing self-healable conjugated polymers for organic electrochemical transistors (OECTs) lie in maintaining good mixed electronic/ionic transport and the need for fast restoration to the original electronic and structural properties after the self-healing process. Herein, we provide the first report of an all-solid-state OECT that is self-healable and possesses good electrical performance, by utilizing a matrix of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and a nonionic surfactant, Triton X-100, as a channel and an ion-conducting poly(vinyl alcohol) hydrogel as a quasi-solid-state polymer electrolyte. The fabricated OECT exhibits high transconductance (maximum 54 mS), an on/off current ratio of ∼1.5 × 103, a fast response time of 6.8 ms, and good operational stability after 68 days of storage. Simultaneously, the OECT showed remarkable self-healing and ion-sensing behaviors and recovered ∼95% of its ion sensitivity after healing. These findings will contribute to the development of high-performance and robust OECTs for wearable bioelectronic devices.

Identification of safety benefits by inter-vehicle crash risk analysis using connected vehicle systems data on Korean freeways.

Worldwide efforts have been made to deploy connected vehicle (CV) technologies in practice. The Korean government has also conducted various projects to fully exploit the benefits of CVs. This study attempted to estimate the safety benefits achievable of CVs based on crash risk analyses, which is a part of a pre-deployment project for CVs on freeways. A nice feature of the CVs in this project is that they are equipped with in-vehicle forward collision warning systems that are capable of providing both the speed of a preceding vehicle and the spacing between the preceding vehicle and a subject vehicle. This technical support enables us to systematically analyze vehicle interactions in terms of traffic safety. The crash potential index (CPI), which is able to analyze vehicle interactions in terms of crash risks, was adopted to quantify the crash potential of CVs when the forward hazardous situation warning (FHSW) information was either provided or not provided. The results of this study show that the average speed decreased by 10.2 % and the time-to-collision (TTC) increased by 5.3 % when warning information was provided. In addition, the achievable reduction in the CPI was approximately 20.7 % due to the provision of warning information. An illustrative demonstration of identifying freeway hazardous spots was also presented as a further application of the CPI analysis. The outcomes of this study will be useful for the establishment of relevant policies to promote CV technologies.

Ionic-Liquid Doping Enables High Transconductance, Fast Response Time, and High Ion Sensitivity in Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) are highly attractive for applications ranging from circuit elements and neuromorphic devices to transducers for biological sensing, and the archetypal channel material is poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), PEDOT:PSS. The operation of OECTs involves the doping and dedoping of a conjugated polymer due to ion intercalation under the application of a gate voltage. However, the challenge is the trade-off in morphology for mixed conduction since good electronic charge transport requires a high degree of ordering among PEDOT chains, while efficient ion uptake and volumetric doping necessitates open and loose packing of the polymer chains. Ionic-liquid-doped PEDOT:PSS that overcomes this limitation is demonstrated. Ionic-liquid-doped OECTs show high transconductance, fast transient response, and high device stability over 3600 switching cycles. The OECTs are further capable of having good ion sensitivity and robust toward physical deformation. These findings pave the way for higher performance bioelectronics and flexible/wearable electronics.

Human Hair Keratin for Biocompatible Flexible and Transient Electronic Devices.

Biomaterials have been attracting attention as a useful building block for biocompatible and bioresorbable electronics due to their nontoxic property and solution processability. In this work, we report the integration of biocompatible keratin from human hair as dielectric layer for organic thin-film transistors (TFTs), with high performance, flexibility, and transient property. The keratin dielectric layer exhibited a high capacitance value of above 1.27 µF/cm2 at 20 Hz due to the formation of electrical double layer. Fully solution-processable TFTs based on p-channel poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b]dithiophen-2-yl)-alt[1,2,5]thiadiazolo[3,4-c]-pyridine] (PCDTPT) and keratin dielectric exhibited high electrical property with a saturation field-effect mobility of 0.35 cm2/(Vs) at a low gate bias of -2 V. We also successfully demonstrate flexible TFTs, which exhibited good mechanical flexibility and electrical stability under bending strain. An artificial electronic synaptic PCDTPT/keratin transistor was also realized and exhibited high-performance synaptic memory effects via simple operation of proton conduction in keratin. An added functionality of using keratin as a substrate was also presented, where similar PCDTPT TFTs with keratin dielectric were built on top of keratin substrate. Finally, we observed that our prepared devices can be degraded in ammonium hydroxide solution, establishing the feasibility of keratin layer as various components of transient electrical devices, including as a substrate and dielectric layer.

Flexible Ionic-Electronic Hybrid Oxide Synaptic TFTs with Programmable Dynamic Plasticity for Brain-Inspired Neuromorphic Computing.

Emulation of biological synapses is necessary for future brain-inspired neuromorphic computational systems that could look beyond the standard von Neuman architecture. Here, artificial synapses based on ionic-electronic hybrid oxide-based transistors on rigid and flexible substrates are demonstrated. The flexible transistors reported here depict a high field-effect mobility of ≈9 cm2 V-1 s-1 with good mechanical performance. Comprehensive learning abilities/synaptic rules like paired-pulse facilitation, excitatory and inhibitory postsynaptic currents, spike-time-dependent plasticity, consolidation, superlinear amplification, and dynamic logic are successfully established depicting concurrent processing and memory functionalities with spatiotemporal correlation. The results present a fully solution processable approach to fabricate artificial synapses for next-generation transparent neural circuits.

Self-Healing Polymer Dielectric for a High Capacitance Gate Insulator.

Self-healing materials are required for development of various flexible electronic devices to repair cracks and ruptures caused by repetitive bending or folding. Specifically, a self-healing dielectric layer has huge potential to achieve healing electronics without mechanical breakdown in flexible operations. Here, we developed a high performance self-healing dielectric layer with an ionic liquid and catechol-functionalized polymer which exhibited a self-healing ability for both bulk and film states under mild self-healing conditions at 55 °C for 30 min. Due to the sufficient ion mobility of the ionic liquid in the polymer matrix, it had a high capacitance value above 1 µF/cm(2) at 20 Hz. Moreover, zinc oxide (ZnO) thin-film transistors (TFTs) with a self-healing dielectric layer exhibited a high field-effect mobility of 16.1 ± 3.07 cm(2) V(-1) s(-1) at a gate bias of 3 V. Even after repetitive self-healing of the dielectric layer from mechanical breaking, the electrical performance of the TFTs was well-maintained.

Fully Solution-Processed and Foldable Metal-Oxide Thin-Film Transistor.

Flexible and foldable thin-film transistors (TFTs) have been widely studied with the objective of achieving high-performance and low-cost flexible TFTs for next-generation displays. In this study, we introduced the fabrication of foldable TFT devices with excellent mechanical stability, high transparency, and high performance by a fully solution process including PI, YOx, In2O3, SWCNTs, IL-PVP, and Ag NWs. The fabricated fully solution-processed TFTs showed a higher transmittance above 86% in the visible range. Additionally, the charge-carrier mobility and Ion/Ioff ratio of them were 7.12 ± 0.43 cm(2)/V·s and 5.53 ± 0.82 × 10(5) at a 3 V low voltage operating, respectively. In particular, the fully solution-processed TFTs showed good electrical characteristics under tensile strain with 1 mm bending and even extreme folding up to a strain of 26.79%. Due to the good compatibility of each component layer, it maintained the charge-carrier mobility over 79% of initial devices after 5,000 cycles of folding test in both the parallel and perpendicular direction with a bending radius of 1 mm. These results show the potential of the fully solution-processed TFTs as flexible TFTs for a next generation devices because of the robust mechanical flexibility, transparency, and high electrical performance of it.

Plasmon-Enhanced Surface Photovoltage of ZnO/Ag Nanogratings.

We investigated the surface photovoltage (SPV) behaviors of ZnO/Ag one-dimensional (1D) nanogratings using Kelvin probe force microscopy (KPFM). The grating structure could couple surface plasmon polaritons (SPPs) with photons, giving rise to strong light confinement at the ZnO/Ag interface. The larger field produced more photo-excited carriers and increased the SPV. SPP excitation influenced the spatial distribution of the photo-excited carriers and their recombination processes. As a result, the SPV relaxation time clearly depended on the wavelength and polarization of the incident light. All of these results suggested that SPV measurement using KPFM should be very useful for studying the plasmonic effects in nanoscale metal/semiconductor hybrid structures.

Direct electron injection into an oxide insulator using a cathode buffer layer.

Injecting charge carriers into the mobile bands of an inorganic oxide insulator (for example, SiO2, HfO2) is a highly complicated task, or even impossible without external energy sources such as photons. This is because oxide insulators exhibit very low electron affinity and high ionization energy levels. Here we show that a ZnO layer acting as a cathode buffer layer permits direct electron injection into the conduction bands of various oxide insulators (for example, SiO2, Ta2O5, HfO2, Al2O3) from a metal cathode. Studies of current-voltage characteristics reveal that the current ohmically passes through the ZnO/oxide-insulator interface. Our findings suggests that the oxide insulators could be used for simply fabricated, transparent and highly stable electronic valves. With this strategy, we demonstrate an electrostatic discharging diode that uses 100-nm SiO2 as an active layer exhibiting an on/off ratio of ∼10(7), and protects the ZnO thin-film transistors from high electrical stresses.

Organic nonvolatile resistive switching memory based on molecularly entrapped fullerene derivative within a diblock copolymer nanostructure.

Organic nonvolatile resistive switching memory is developed via selective incorporation of fullerene derivatives, [6,6]-phenyl-C61 butyric acid methyl ester (PCBM), into the nanostructure of self-assembled poly(styrene-b-methyl methacrylate) (PS10 -b-PMMA130) diblock copolymer. PS10 -b-PMMA130 diblock copolymer provides a spatially ordered nanotemplate with a 10-nm PS nanosphere domain surrounded by a PMMA matrix. Spin casting of the blend solution of PS10 -b-PMMA130 and PCBM spontaneously forms smooth films without PCBM aggregation in which PCBM molecules are incorporated within a PS nanosphere domain of PS10 -b-PMMA130 nanostructure by preferential intermixing propensity of PCBM and PS. Based on the well-defined PS10-b-PMMA 130/PCBM nanostructure, resistive random access memory (ReRAM) exhibits significantly improved bipolar-switching behavior with stable and reproducible properties at low operating voltages (RESET at 1.3 V and SET at -1.5 V) under ambient conditions. Finally, flexible memory devices are achieved using a nanostructured PS10 -b-PMMA130 /PCBM composite in which no significant degradation of electrical properties is observed before and after bending.

Analysis of cyclic pyrolysis products formed from amino acid monomer.

Amino acid was mixed with silica and tetramethylammonium hydroxide (TMAH) to favor pyrolysis of amino acid monomer. The pyrolysis products formed from amino acid monomer were using GC/MS and GC. 20 amino acids of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were analyzed. The pyrolysis products were divided into cyclic and non-cyclic products. Among the 20 amino acids, arginine, asparagine, glutamic acid, glutamine, histidine, lysine, and phenylalanine generated cyclic pyrolysis products of the monomer. New cyclic pyrolysis products were formed by isolation of amino acid monomers. They commonly had polar side functional groups to 5-, 6-, or 7-membered ring structure. Arginine, asparagine, glutamic acid, glutamine, histidine, and phenylalanine generated only 5- or 6-membered ring products. However, lysine generated both 6- and 7-membered ring compounds. Variations of the relative intensities of the cyclic pyrolysis products with the pyrolysis temperature and amino acid concentration were also investigated.