Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Funnel Devices Based on Asymmetrically Strained Transition Metal Dichalcogenides.

The strain applied to transition metal dichalcogenides (TMDs) reduces their energy bandgap, and local strains result in a funnel-like band structure in which funneled excitons move toward the most strained region. Herein, a funnel device based on asymmetrically strained WS2 and MoS2 is reported. Asymmetric strains are induced by transferring the TMD flakes onto a fork-shaped SU-8 microstructure. Raman and photoluminescence spectra peaks are shifted according to the morphology of the SU-8 microstructure, indicating the application of asymmetric strains to the TMDs. To investigate whether funneled excitons can be converted to electrical currents, various devices are constructed by depositing symmetric and asymmetric electrodes onto the strained TMDs. The scanning photocurrent mapping images follow a fork-shaped pattern, indicating probable conversion of the funneled excitons into electrical currents. In the case of the funnel devices with asymmetric Au and Al electrodes, short-circuit current (ISC ) of WS2 is enhanced by the strains, whereas ISC of MoS2 is suppressed because the Schottky barrier lowers with increasing strain for the MoS2 . These results demonstrate that the funnel devices can be implemented using asymmetrically strained TMDs and the effect of strains on the Schottky barrier is dependent on the TMD used.

Distinctive role of inflammation in tissue repair and regeneration.

Inflammation is an essential host defense mechanism in response to microbial infection and tissue injury. In addition to its well-established role in infection, inflammation is actively involved in the repair of damaged tissues and restoration of homeostatic conditions after tissue injury. The intensity of the inflammatory response and types of cells involved in inflammation have a significant impact on the quality of tissue repair. Numerous immune cell subtypes participate in tissue repair and regeneration. In particular, immune cell-derived secretants, including cytokines and growth factors, can actively modulate the proliferation of resident stem cells or progenitor cells to facilitate tissue regeneration. These findings highlight the importance of inflammation during tissue repair and regeneration; however, the precise role of immune cells in tissue regeneration remains unclear. In this review, we summarize the current knowledge on the contribution of specific immune cell types to tissue repair and regeneration. We also discuss how inflammation affects the final outcome of tissue regeneration.

The effect of watching OTT late at night on the sleep pattern of users.

This study aimed to answer the question of how media users will reallocate their sleep time when their main content channel changes from real-time broadcasting to selective viewing through the over-the-top (OTT) media streaming service. To draw a causal inference between OTT consumption and sleep patterns, the difference-in-difference (DID) estimation method was applied. With the DID approach, a clear distinction between treatment and control groups is essential because the main treatment effects can be screened by the compounding effects. While the conventional way of dividing two groups relies on the selection of limited variables, this study adopted random forest nearest-neighbor propensity score matching based on a machine learning algorithm to divide the two groups. This allows for meticulous matching of the two groups except for treatment. Results show that watching OTT late at night has a significant effect on reducing the total sleep duration on average by about 18-20 min (maximum about 30 min at 95% confidence level) and delaying bedtime by about 18 min (maximum about 26 min at 95% confidence level). This study showed that the selective viewing of content through OTT has the advantage of widening the range of content choices for media users and helping in arranging their time more autonomously, but watching content through OTT late at night leads to media users' departure from the existing sleep routine.

Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model.

Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy.

Changes in regional knowledge bases and its effect on local labour markets in the midst of transition: Evidence from France over 1985-2015.

In the 2000s, the European labour market experienced a number of significant changes including the transition to a more knowledge-intensive economy as well as the introduction of various economic policies (e.g. Eurozone, subsidized jobs, and social tax cuts). In times like these, the role of knowledge, which is essentially the driving force of innovation and thus promoting technological change and economic growth, is shifting due to new labour market conditions. The present study aims to explore how processes of local knowledge bases have been altered in this transformative environment and how these have impacted on local employment growth. The investigation considers three different knowledge bases in conjunction, incl. knowledge size, knowledge creation, and knowledge application. The study is based on an econometric analysis of a panel of 94 France NUTS-3 regions covering the period 1985-2015, utilizing patent data from European Patent Office (EPO) Statistical Patent Database (PATSTAT), and regional data from European Regional Database (ERD). The result shows that the role of knowledge for employment growth has indeed changed towards more specialized inputs in applications while the importance of greater knowledge size remains still important.

Ferroelastic-Ferroelectric Multiferroicity in van der Waals Rhenium Dichalcogenides.

2D multiferroics with combined ferroic orders have gained attention owing to their novel functionality and underlying science. Intrinsic ferroelastic-ferroelectric multiferroicity in single-crystalline van der Waals rhenium dichalcogenides, whose symmetries are broken by the Peierls distortion and layer-stacking order, is demonstrated. Ferroelastic switching of the domain orientation and accompanying anisotropic properties is achieved with 1% uniaxial strain using the polymer encapsulation method. Based on the electron localization function and bond dissociation energy of the Re-Re bonds, the change in bond configuration during the evolution of the domain wall and the preferred switching between the two specific orientation states are explained. Furthermore, the ferroelastic switching of ferroelectric polarization is confirmed using the photovoltaic effect. The study provides insights into the reversible bond-switching process and potential applications based on 2D multiferroicity.

Estimating cost of fighting against fake news during catastrophic situations.

As the battle with COVID-19 continues, an Infodemic problem has been raised. Even though the distribution of false news in national disaster situations has been reported for a long time, little attention has been given to the quantitative research of the fake news problem from the audience's perspective. This study, therefore, aims to estimate how much tax taxpayers would gladly pay for a virtual public-run fact-checking system. Using a one-and-one-half bounded dichotomous choice contingent valuation method, a survey was conducted on 525 respondents in Korea, and the spike model was applied to distinguish zero willingness-to-pay (WTP). The results show that a household's WTP for the public fact-checking system is 10,652 KRW (9 USD), on average, in the form of income tax for five years. Given the amount is a regular payment in perpetuity, the total WTP is estimated at 23 billion KRW ($196 M) every year. The result also shows that an individual's WTP increases as his or her psychological damage caused by fake news is high, as well as his or her high reliance on news in a disaster situation.

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.

BACKGROUND: Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy. METHODS: Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology. RESULTS: Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the ß-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier. CONCLUSION: EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.

Ishige okamurae Ameliorates Methylglyoxal-Induced Nephrotoxicity via Reducing Oxidative Stress, RAGE Protein Expression, and Modulating MAPK, Nrf2/ARE Signaling Pathway in Mouse Glomerular Mesangial Cells.

Advanced glycation end-products (AGEs) such as methylglyoxal (MGO) play a vital role in the pathogenesis of nephropathy, a diabetic complication. In the present study, we evaluated the anti-glycation and renal protective properties of Ishige okamurae extract (IOE) against AGE-induced oxidative stress. HPLC analysis confirmed that bioactive phlorotannins such as diphlorethohydroxycarmalol and ishophloroglucin A are predominantly present in IOE. IOE showed strong anti-glycation activities via inhibition of AGE formation, inhibition of AGE-protein cross-linking, and breaking of AGE-protein cross-links. In addition, in vitro studies using mesangial cells demonstrated that IOE effectively suppressed intracellular reactive oxygen species production, intracellular MGO accumulation, and apoptotic cell death by MGO-induced oxidative stress, in addition to regulating the expression of proteins involved in the receptor for AGEs and nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathways. Therefore, IOE can serve as a natural therapeutic agent for the management of AGE-related nephropathy.

The nature of ICT in technology convergence: A knowledge-based network analysis.

This study aims to understand the nature of information and communication technology in technology convergence. We form a knowledge network by applying social network theories to Korean patent data collected from the European Patent Organization. A knowledge network consists of nodes representing technology sectors identified by their International Patent Classification codes and edges that link International Patent Classification codes when they appear concurrently in a patent. We test the proposed hypotheses using four indices (degree centrality, E-I index, entropy index, and clustering coefficient). The results show that information and communication technology is easily attached but tends to converge with similar technology and has the greatest influence on technology convergence over other technologies. This study is expected to help practitioners and policymakers understand the structure and interaction mechanisms of technology from a systematic perspective and improve national-level technology policies.

Distinct Features of Brain-Resident Macrophages: Microglia and Non-Parenchymal Brain Macrophages.

Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.

Pentacyanoammineferrate-Based Non-Enzymatic Electrochemical Biosensing Platform for Selective Uric Acid Measurement.

The electrochemical-based detection of uric acid (UA) is widely used for diagnostic purposes. However, various interfering species such as ascorbic acid, dopamine, and glucose can affect electrochemical signals, and hence there is an outstanding need to develop improved sensing platforms to detect UA with high selectivity. Herein, we report a pentagonal mediator-based non-enzymatic electrochemical biosensing platform to selectively measure UA in the presence of interfering species. The working electrode was fabricated by electrodepositing polymerized 1-vinylimidazole (PVI), which has an imidazole ligand, onto indium tin oxide (ITO), and then conjugating nickel ions to the PVI-coated ITO electrode. Electrode performance was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements and integrated together with pentacyanoammineferrate, which can bind to the amine groups of UA and function as an electron transferring mediator. The experimental results showed a wide linear range of UA concentration-dependent responses and the multi-potential step (MPS) technique facilitated selective detection of UA in the presence of physiologically relevant interfering species. Altogether, these findings support that pentacyanoammineferrate-based non-enzymatic electrodes are suitable biosensing platforms for the selective measurement of UA, and such approaches could potentially be extended to other bioanalytes as well.

Rectifying optoelectronic memory based on WSe2/graphene heterostructures.

van der Waals heterostructures composed of two-dimensional materials vertically stacked have been extensively studied to develop various multifunctional devices. Here, we report WSe2/graphene heterostructure devices with a top floating gate that can serve as multifunctional devices. They exhibit gate-controlled rectification inversion, rectified nonvolatile memory effects, and multilevel optoelectronic memory effects. Depending on the polarity of the gate voltage pulses (V Gp), electrons or holes can be trapped in the floating gate, resulting in rectified nonvolatile memory properties. Furthermore, upon repeated illumination with laser pulses, positive or negative staircase photoconductivity is observed depending on the history of V Gp, which is ascribed to the tunneling of electrons or holes between the WSe2 channel and the floating gate. These multifunctional devices can be used to emulate excitatory and inhibitory synapses that have different neurotransmitters. Various synaptic functions, such as potentiation/depression curves and spike-timing-dependent plasticity, have been also implemented using these devices. In particular, 128 optoelectronic memory states with nonlinearity less than 1 can be achieved by controlling applied laser pulses and V Gp, suggesting that the WSe2/graphene heterostructure devices with a top floating gate can be applied to optoelectronic synapse devices.

Immunopathogenesis of ANCA-Associated Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

Towards Understanding Tuberculosis-Related Issues in North Korea: A Narrative Review of North Korean Literature.

BACKGROUND: North Korea is one of the 30 countries with the highest tuberculosis (TB) and drug-resistant TB burdened. To understand the medical issues and research trends associated with TB in North Korea, we performed a comprehensive review of articles related to clinical and laboratory research on TB published in North Korean medical journals. METHODS: We reviewed all types of TB-related articles published in nine North Korean medical journals (Yebang uihak: Preventive medicine; Koryo uihak: Korea Medicine; Choson uihak: Chosun Medicine; Naekwa: Internal Medicine; Soa, sanbuinkwa: Pediatrics, Obstetrics, and Gynecology, Surgery; Uihak: Medicine; Kich'o uihak: Basic Medicine; and Choson yakhak: Chosun Pharmacy). We classified the articles according to the type and field of study and analyzed the data qualitatively to gain insights. RESULTS: We reviewed 106 articles (one- or two-page length) written in Korean, including reviews (n=43), original articles (n=52), and case reports (n=8). They were classified as follows: articles on diagnosis (n=52, 49%) and treatment (n=39, 37%). None of the studies investigated the commercialized molecular diagnosis systems such as Xpert MTB/RIF. Directly Observed Treatment, Short-course was reported as the basic treatment approach. Furthermore, six studies used Korean traditional medicines for treating TB, with one of them containing snake venom. CONCLUSION: The articles were not sufficiently detailed. Original articles on the treatment of multi-drug resistant TB were not found, and those on latent tuberculosis infection and nontuberculous mycobacteria were limited. To understand the current medical issues associated with TB in North Korea, articles from these nine journals were not sufficient.

Measures to Promote Rural Healthcare Tourism with a Scientific Evidence-Based Approach.

The present study aimed to evaluate the effects of physical activities on human health in forests in countryside and rural areas. The test experiment was conducted in a countryside forest, whereas the controlled experiment was conducted in an urban area where the study participants resided. A total of 22 participants (aged 20.9 ± 1.3 years) were evaluated in this study. Heart rate variability and salivary cortisol level were used as indices of physiological conditions, and semantic differential method, profile of mood states (POMS), and state-trait anxiety inventory (STAI) were used to evaluate the participants' emotional states. The participants were asked to walk around forest and urban areas for 15 min. The results were as follows. As compared to the urban area, in the forest area, (1) the power of the high-frequency (HF) component of the heart rate variability (HRV) was significantly higher; (2) low-frequency (LF)/(LF + HF) was significantly lower; (3) salivary cortisol level was significantly lower; (4) the participants felt more comfortable, natural, relaxed, and less anxious and showed higher levels of positive emotions and lower levels of negative emotions. Consequently, walking in the forest area induces relaxing short-term physiological and psychological effects on young people living in urban areas.

Multilevel MoS2 Optical Memory with Photoresponsive Top Floating Gates.

Optoelectronic memory devices, whose states can be controlled using electrical optical signals, are receiving much attention for their potential applications in image sensing and parallel data transmission and processes. Here, we report MoS2-based devices with top floating gates of Au, graphene, and MoS2. Unlike conventional floating gate memory devices, our devices have the photoresponsive floating gate at the top, acting as a charge trapping layer. Stable and reliable switching with an on/off ratio of ∼106 and a retention time of >104 s is achieved by illumination with 405 nm light pulses as well as application of gate voltage pulses. However, upon illumination with 532 or 635 nm light pulses, multilevel optical memory effects are observed, which are dependent on the wavelength and the optical exposure dosage. In addition, compared to the device employing a graphene floating gate, the device with an MoS2 floating gate is more sensitive to light, suggesting that the multilevel optical memory properties originate from photoexcited carriers in the top floating gate and can be modulated by adjusting the top floating gate materials. The structure of the top floating gate may open up a new way to novel optoelectronic memory devices.

The Effect of a Reduced Statutory Workweek on Familial Long-Term Care in Korea.

OBJECTIVES: We examine how statutory workweeks affect workers' provision of long-term care for their non-coresident elderly parents. METHOD: The Korean government reduced its statutory workweek from 44 to 40 hr, gradually from larger to smaller establishments, between 2004 and 2011. Using multiple regressions, we assess how the reduction affected visits, financial transfers, and in-kind transfers to parents. Annual longitudinal data come from the 2005 to 2013 waves of the Korea Labor and Income Panel Study. RESULTS: The reduction caused an increase in the frequency of visits and in-kind transfers among male workers, with no significant impact on their financial transfers. Among female workers, we found no impact on any outcomes. DISCUSSION: We interpret the findings within the context of developed Asian countries with long work hours and Confucian traditions, and suggest regulating workweeks as a policy tool to encourage familial long-term care in the rapidly aging societies.

Highly efficient new hole injection materials for organic light emitting diodes base on phenothiazine derivatives.

New hole injection materials for OLED based on phenothiazine were synthesized, and the electro-optical properties of synthesized materials were examined by through UV-Vis. and photoluminescence spectroscopy as well as cyclic voltammetry. 1-NDD-t-BPBP and 2-NDD-t-BPBP showed Tg of 180 and 177 °C. These are higher than that (110 °C) of 2-TNATA, commercial HIL material. As for the HOMO level of the synthesized materials, 1-NDD-t-BPBP and 2-NDD-t-BPBP were 4.99 and 5.02 eV, indicating well-matched values between HOMO (4.8 eV) of ITO and HOMO (5.4 eV) of NPB, HTL material. In addition, judging from the fact that the synthesized materials both barely showed any absorption in the range of over 450 nm, the synthesized materials could be effectively used as an HIL material. The synthesized materials were used as the HIL in OLED device, yielding luminance efficiencies of 4.51 cd/A (1-NDD-t-BPBP) and 4.44 cd/A (2-NDD-t-BPBP). These results indicated that 1-NDD-t-BPBP shows more excellent luminance efficiency which is about 11% improved over 2-TNATA a commercial HIL material.