E-Cigarette Nicotine Delivery Among Young Adults by Nicotine Form, Concentration, and Flavor: A Crossover Randomized Clinical Trial.

Importance: Concerns have been raised about the abuse liability of modern e-cigarettes that use acidic additives to form nicotine salts, making the inhalation of nicotine smoother than freebase nicotine. Objective: To examine the effects of nicotine form and concentration and e-liquid flavor on subjective effects ratings, vaping behavior, and nicotine uptake among young adults who use e-cigarettes. Design, Setting, and Participants: In this single-blind, within-participant, crossover randomized clinical trial, a convenience sample of young adults aged 21 to 25 years who currently used e-cigarettes was recruited from December 2021 to August 2023, for in-person research laboratory visits in Columbus, Ohio. Interventions: Participants completed up to 9 vaping sessions, starting with their usual e-cigarette brand in the first session followed by 1 of 8 laboratory-prepared e-liquids in a randomly assigned order in each subsequent session. Prepared e-liquids varied by nicotine form (salt-based vs freebase), nicotine concentration (5% vs 1% weight per weight), and flavor (menthol vs tobacco). Each session included a 5-minute, 10-puff standardized vaping period followed by 30 minutes of ad libitum vaping. Main Outcomes and Measures: At 4 time points (0, 5, 10, and 35 minutes) during each vaping session, plasma samples were collected for assessing nicotine uptake, and self-reports of urges, craving, and withdrawal were collected via questionnaires. Positive subjective effects were self-reported after 35 minutes of vaping using a visual analog scale; urges and cravings were reported using the Questionnaire of Smoking Urges (QSU). Puff topography data were collected throughout each vaping session. Results: Seventy-two participants (mean [SD] age, 22.4 [1.4] years; 42 [58.3%] female) who sampled at least 1 laboratory-prepared e-liquid composed the analytic sample. Salt-based (vs freebase) nicotine e-liquids increased nicotine intake, with 5% salt-based e-liquids delivering the highest mean plasma levels of nicotine (11.2 ng/mL [95% CI, 9.3-13.2 ng/mL] at 5 minutes; 17.2 ng/mL [95% CI, 14.3-20.1 ng/mL] at 35 minutes) irrespective of flavors. Higher positive subjective effect ratings (eg, for liking) were received by salt-based (42.8; 95% CI, 39.4-46.1) vs freebase (32.0; 95% CI, 28.6-35.3) nicotine, 1% (43.4; 95% CI, 40.2-46.6) vs 5% (31.2; 95% CI, 27.7-34.6) nicotine, and menthol-flavored (43.2; 95% CI, 39.7-46.7) vs tobacco-flavored (31.5; 95% CI, 28.4-34.7) e-liquids. Salt-based and 1% but not menthol-flavored nicotine elicited more intense puffing (eg, 25% [95% CI, 12%-40%] more total puffs for nicotine salts vs freebase). All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0.5] vs 16.7 [0.5]). Conclusions and Relevance: In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes. Trial Registration: ClinicalTrials.gov Identifier: NCT05458895.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

BACKGROUND: This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). METHODS: Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). RESULTS: Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. CONCLUSIONS: Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Ustekinumab was well-tolerated and safe for Koran patients with Crohn's disease with no new safety signal as induction and maintenance therapy. Biologic-naïve patients exhibited better effectiveness outcomes, whereas combination therapy with immunomodulators was not superior to ustekinumab monotherapy.

CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a fabry disease vasculopathy model derived from human induced pluripotent stem cells.

BACKGROUND AND AIMS: The objective of this study was to investigate the efficacy of CRISPR/Cas9-mediated A4GALT suppression in rescuing endothelial dysfunction in Fabry disease (FD) endothelial cells (FD-ECs) derived from human induced pluripotent stem cells (hiPSCs). METHODS: We differentiated hiPSCs (WT (wild-type), WTC-11), GLA-mutant hiPSCs (GLA-KO, CMC-Fb-002), and CRISPR/Cas9-mediated A4GALT-KO hiPSCs (GLA/A4GALT-KO, Fb-002-A4GALT-KO) into ECs and compared FD phenotypes and endothelial dysfunction. We also analyzed the effect of A4GALT suppression on reactive oxygen species (ROS) formation and transcriptome profiles through RNA sequencing. RESULTS: GLA-mutant hiPSC-ECs (GLA-KO and CMC-Fb-002) showed downregulated expression of EC markers and significantly reduced α-GalA expression with increased Gb-3 deposition and intra-lysosomal inclusion bodies. However, CRISPR/Cas9-mediated A4GALT suppression in GLA/A4GALT-KO and Fb-002-A4GALT-KO hiPSC-ECs increased expression levels of EC markers and rescued these FD phenotypes. GLA-mutant hiPSC-ECs failed to form tube-like structure in tube formation assays, showing significantly decreased migration of cells into the scratched wound area. In contrast, A4GALT suppression improved tube formation and cell migration capacity. Western blot analysis revealed that MAPK and AKT phosphorylation levels were downregulated while SOD and catalase were upregulated in GLA-KO hiPSC-ECs. However, suppression of A4GALT restored these protein alterations. RNA sequencing analysis demonstrated significant transcriptome changes in GLA-mutant EC, especially in angiogenesis, cell death, and cellular response to oxidative stress. However, these were effectively restored in GLA/A4GALT-KO hiPSC-ECs. CONCLUSIONS: CRISPR/Cas9-mediated A4GALT suppression rescued FD phenotype and endothelial dysfunction in GLA-mutant hiPSC-ECs, presenting a potential therapeutic approach for FD-vasculopathy.

Advancements in Flexible Nanogenerators: Polyvinylidene Fluoride-Based Nanofiber Utilizing Electrospinning.

With the gradual miniaturization of electronic devices and the increasing interest in wearable devices, flexible microelectronics is being actively studied. Owing to the limitations of existing battery systems corresponding to miniaturization, there is a need for flexible alternative power sources. Accordingly, energy harvesting from surrounding environmental systems using fluorinated polymers with piezoelectric properties has received significant attention. Among them, polyvinylidene fluoride (PVDF) and PVDF co-polymers have been researched as representative organo-piezoelectric materials because of their excellent piezoelectric properties, mechanical flexibility, thermal stability, and light weight. Electrospinning is an effective method for fabricating nanofibrous meshes with superior surface-to-volume ratios from polymer solutions. During electrospinning, the polymer solution is subjected to mechanical stretching and in situ poling, corresponding to an external strong electric field. Consequently, the fraction of the piezoelectric ß-phase in PVDF can be improved by the electrospinning process, and enhanced harvesting output can be realized. An overview of electrospun piezoelectric fibrous meshes composed of PVDF or PVDF co-polymers to be utilized is presented, and the recent progress in enhancement methods for harvesting output, such as fiber alignment, doping with various nanofillers, and coaxial fibers, is discussed. Additionally, other applications of these meshes as sensors are reviewed.

Retrorectus Ventral Hernia Repair Utilizing T-line Hernia Mesh: Technical Descriptions.

The T-line hernia mesh is a synthetic, polypropylene mesh with mesh suture extensions designed to prevent anchor point failure by evenly distributing tension across the soft tissue. Previous studies have demonstrated the success of onlay ventral hernia repair with T-line hernia mesh, but retrorectus applications of the mesh have not yet been characterized. This technique article illustrates technical descriptions and clinical applications of the T-line hernia mesh in the retrorectus plane.

Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies.

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid ß and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor-dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter-dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.

Generation of green fluorescent protein reporter knock-in iPSC line at the 3'UTR region of the KLOTHO locus.

We generated a human induced pluripotent stem cell (hiPSC) line (CMCi014-A-78) expressing a GFP reporter in the 3'-UTR region of the KLOTHO locus using CRISPR/Cas9-mediated homologous recombination to screen for candidates regulating KLOTHO. The established cell line exhibits a normal karyotype, typical stem cell morphology, expression of pluripotency markers, and the ability to differentiate into the three germ layers. Consequently, this hiPSC line could serve as a valuable resource for screening KLOTHO regulators in hiPSC-derived target cells or organoids.

Interpretable deep learning model to predict lymph node metastasis in early gastric cancer using whole slide images.

In early gastric cancer (EGC), the presence of lymph node metastasis (LNM) is a crucial factor for determining the treatment options. Endoscopic resection is used for treatment of EGC with minimal risk of LNM. However, owing to the lack of definitive criteria for identifying patients who require additional surgery, some patients undergo unnecessary additional surgery. Considering that histopathologic patterns are significant factor for predicting lymph node metastasis in gastric cancer, we aimed to develop a machine learning algorithm which can predict LNM status using hematoxylin and eosin (H&E)-stained images. The images were obtained from several institutions. Our pipeline comprised two sequential approaches including a feature extractor and a risk classifier. For the feature extractor, a segmentation network (DeepLabV3+) was trained on 243 WSIs across three datasets to differentiate each histological subtype. The risk classifier was trained with XGBoost using 70 morphological features inferred from the trained feature extractor. The trained segmentation network, the feature extractor, achieved high performance, with pixel accuracies of 0.9348 and 0.8939 for the internal and external datasets in patch level, respectively. The risk classifier achieved an overall AUC of 0.75 in predicting LNM status. Remarkably, one of the datasets also showed a promising result with an AUC of 0.92. This is the first multi-institution study to develop machine learning algorithm for predicting LNM status in patients with EGC using H&E-stained histopathology images. Our findings have the potential to improve the selection of patients who require surgery among those with EGC showing high-risk histological features.

Analysis of prefrontal cerebral blood volume and flow changes in ESKD patients undergoing hemodialysis using functional near-infrared spectroscopy.

BACKGROUND: End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. METHODS: ESKD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 - HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. RESULTS: Thirty hemodialysis patients were analyzed. The change in HbO2, HbT, and HbD levels showed significant differences according to the hemodialysis period. Between the pre-HD and post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p = .046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p = .029). Additionally, between pre-HD and post-HD periods, HbD tended to increase (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p = .094). CONCLUSIONS: We demonstrated that during one hemodialysis session, the relative change in prefrontal CBV increased post-HD compared with pre-HD. These results are expected to help understanding the mechanisms underlying the effects of hemodialysis on brain function.

Mode of Action of Antimicrobial Potential Protease SH21 Derived from Bacillus siamensis.

Global public health is facing a major issue with emerging resistance to antimicrobial agents. Antimicrobial agents that are currently on the market are strong and efficient, but it has not been ruled out that these medications will eventually cause resistance to bacteria. Exploring novel bioactive compounds derived from natural sources is therefore, crucial to meet future demands. The present study evaluated the mode of action of the antimicrobial potential protease enzyme SH21. Protease SH21 exhibited antimicrobial activity, strong heat stability (up to 100 °C), and pH stability (pH 3.0 to 9.0). In terms of mode of action, we found that protease SH21 was able to disrupt the bacterial cell membrane as the results of the nucleotide leakage and cell membrane permeability assay. In addition, we also checked inner membrane permeability by PI uptake assay which suggested that protease SH21 has the ability to enter the bacterial cell membrane. Our results revealed that the antimicrobial protease SH21 might be a promising candidate for treating microbial infections.

Noncontact Sensors for Vital Signs Measurement: A Narrative Review.

Vital signs are crucial for monitoring changes in patient health status. This review compared the performance of noncontact sensors with traditional methods for measuring vital signs and investigated the clinical feasibility of noncontact sensors for medical use. We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for articles published through September 30, 2023, and used the key search terms "vital sign," "monitoring," and "sensor" to identify relevant articles. We included studies that measured vital signs using traditional methods and noncontact sensors and excluded articles not written in English, case reports, reviews, and conference presentations. In total, 129 studies were identified, and eligible articles were selected based on their titles, abstracts, and full texts. Three articles were finally included in the review, and the types of noncontact sensors used in each selected study were an impulse radio ultrawideband radar, a microbend fiber-optic sensor, and a mat-type air pressure sensor. Participants included neonates in the neonatal intensive care unit, patients with sleep apnea, and patients with coronavirus disease. Their heart rate, respiratory rate, blood pressure, body temperature, and arterial oxygen saturation were measured. Studies have demonstrated that the performance of noncontact sensors is comparable to that of traditional methods of vital signs measurement. Noncontact sensors have the potential to alleviate concerns related to skin disorders associated with traditional skin-contact vital signs measurement methods, reduce the workload for healthcare providers, and enhance patient comfort. This article reviews the medical use of noncontact sensors for measuring vital signs and aimed to determine their potential clinical applicability.

Deep Learning Model Using Stool Pictures for Predicting Endoscopic Mucosal Inflammation in Patients With Ulcerative Colitis.

INTRODUCTION: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. METHODS: This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). RESULTS: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002). DISCUSSION: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC.

Frailty is a predictor for worse outcomes in patients hospitalized with Clostridioides difficile infection.

Background: Frailty has major health implications for affected patients and is widely used in the perioperative risk assessment. The Hospital Frailty Risk Score (HFRS) is a validated score that utilizes administrative billing data to identify patients at higher risk because of frailty. We investigated the utility of the HFRS in patients with Clostridioides difficile infection (CDI) to determine whether they were at risk for worse outcomes and higher healthcare resource utilization. Methods: Using the 2017 National Inpatient Sample, we identified all adults with a primary diagnosis of CDI. We classified patients into 2 groups: those who had an HFRS <5 (NonFrailCDI) and those with a score ≥5 (FrailCDI). We assessed differences in hospital outcomes and healthcare resource utilization based on frailty status. Results: We identified 93,810 hospitalizations, of which 54,300 (57.88%) were FrailCDI. FrailCDI patients were at higher risk for fulminant CDI (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.6-2.3), requiring colectomy (OR 4.1, 95%CI 1.5-11.2), and inpatient mortality (OR 4.5, 95%CI 2.8-7.1). Furthermore, FrailCDI patients had higher odds of requiring Intensive Care Unit admission (OR 13.7, 95%CI 6.3-29.9) or transfer to another facility on discharge (OR 2.2, 95%CI 2.0-2.4), and had longer hospital stays and higher total charges when compared with NonFrailCDI. Conclusions: Frailty as defined by the HFRS is an independent factor for worse outcomes and higher healthcare utilization in adults admitted for CDI. Risk stratifying patients by frailty may improve outcomes.

Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies.

Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer Disease (AD), and recent proteomic studies highlight a disruption of glial carbohydrate metabolism with disease progression. Here, we report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN) in the first step of the kynurenine pathway, rescues hippocampal memory function and plasticity in preclinical models of amyloid and tau pathology by restoring astrocytic metabolic support of neurons. Activation of IDO1 in astrocytes by amyloid-beta 42 and tau oligomers, two major pathological effectors in AD, increases KYN and suppresses glycolysis in an AhR-dependent manner. Conversely, pharmacological IDO1 inhibition restores glycolysis and lactate production. In amyloid-producing APP Swe -PS1 ΔE9 and 5XFAD mice and in tau-producing P301S mice, IDO1 inhibition restores spatial memory and improves hippocampal glucose metabolism by metabolomic and MALDI-MS analyses. IDO1 blockade also rescues hippocampal long-term potentiation (LTP) in a monocarboxylate transporter (MCT)-dependent manner, suggesting that IDO1 activity disrupts astrocytic metabolic support of neurons. Indeed, in vitro mass-labeling of human astrocytes demonstrates that IDO1 regulates astrocyte generation of lactate that is then taken up by human neurons. In co-cultures of astrocytes and neurons derived from AD subjects, deficient astrocyte lactate transfer to neurons was corrected by IDO1 inhibition, resulting in improved neuronal glucose metabolism. Thus, IDO1 activity disrupts astrocytic metabolic support of neurons across both amyloid and tau pathologies and in a model of AD iPSC-derived neurons. These findings also suggest that IDO1 inhibitors developed for adjunctive therapy in cancer could be repurposed for treatment of amyloid- and tau-mediated neurodegenerative diseases.

Early Parenting Interventions to Enhance Development in Infants and Children Born Prematurely: A Systematic Review and Meta-Analysis.

INTRODUCTION: Parenting interventions have the potential to become effective strategies for improving the developmental trajectories of infants and children born prematurely. However, the effectiveness of parenting interventions is not well understood. METHODS: A literature search was conducted in five databases. A total of 24 studies involving 3,636 participants were included for review. RESULTS: The results showed a significant effect in cognition, language, motor development, and behavioral problems of children born prematurely. Parenting stress, anxiety, and interactive behaviors showed significant effect size. DISCUSSION: This review focuses on interventions that employ scaffolding parenting strategies to enhance the development of children born prematurely. Efforts should continue to empower parents through effective and sustainable parenting interventions to improve the quality of life of preterm children.

Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids.

Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly identified in cases previously deemed CKD of unknown etiology. However, despite these diagnostic strides, research into disease pathogenesis and novel drug development faces significant hurdles, chiefly due to the dearth of appropriate animal models and the challenges posed by limited patient cohorts in clinical studies. Conversely, the advent and utilization of human-induced pluripotent stem cells (hiPSCs) offer a promising avenue for genetic kidney disease research. Particularly, the development of hiPSC-derived kidney organoid systems presents a novel platform for investigating various forms of genetic kidney diseases. Moreover, the integration of the CRISPR/Cas9 technique into this system holds immense potential for efficient research on genetic kidney diseases. This review aims to explore the applications of in vitro kidney organoids generated from hiPSCs in the study of diverse genetic kidney diseases. Additionally, it will delve into the limitations of this research platform and outline future perspectives for advancing research in this crucial area.

Lavandula angustifolia Mill. inhibits high glucose and nicotine-induced Ca2+ influx in microglia and neuron-like cells via two distinct mechanisms.

Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca2+ ([Ca2+]i) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms.

Scalable CIGS Solar Cells Employing a New Device Design of Nontoxic Buffer Layer and Microgrid Electrode.

The efficiency of copper indium gallium selenide (CIGS) solar cells that use transparent conductive oxide (TCO) as the top electrode decreases significantly as the device area increases owing to the poor electrical properties of TCO. Therefore, high-efficiency, large-area CIGS solar cells require the development of a novel top electrode with high transmittance and conductivity. In this study, a microgrid/TCO hybrid electrode is designed to minimize the optical and resistive losses that may occur in the top electrode of a CIGS solar cell. In addition, the buffer layer of the CIGS solar cells is changed from the conventional CdS buffer to a dry-processed wide-band gap ZnMgO (ZMO) buffer, resulting in increased device efficiency by minimizing parasitic absorption in the short-wavelength region. By optimizing the combination of ZMO buffer and the microgrid/TCO hybrid electrode, a device efficiency of up to 20.5% (with antireflection layers) is achieved over a small device area of 5 mm × 5 mm (total area). Moreover, CIGS solar cells with an increased device area of up to 20 mm × 70 mm (total area) exhibit an efficiency of up to 19.7% (with antireflection layers) when a microgrid/TCO hybrid electrode is applied. Thus, this study demonstrates the potential for high-efficiency, large-area CIGS solar cells with novel microgrid electrodes.