Challenges in drug development of neurological diseases remain mainly ascribed to the blood-brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains ...difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.
The uniform growth of single-crystal graphene over wafer-scale areas remains a challenge in the commercial-level manufacturability of various electronic, photonic, mechanical, and other devices based ...on graphene. Here, we describe wafer-scale growth of wrinkle-free single-crystal monolayer graphene on silicon wafer using a hydrogen-terminated germanium buffer layer. The anisotropic twofold symmetry of the germanium (110) surface allowed unidirectional alignment of multiple seeds, which were merged to uniform single-crystal graphene with predefined orientation. Furthermore, the weak interaction between graphene and underlying hydrogen-terminated germanium surface enabled the facile etch-free dry transfer of graphene and the recycling of the germanium substrate for continual graphene growth.
Abstract
For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and ...large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm
2
and a greater than 8% efficiency for a cell area larger than 2 cm
2
of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.
The aim of this study was to establish ethnic- and gender-specific cut-off values of triglycerides and glucose index (TyG index) for clinical usefulness in a representative sample of Mexican ...American, Non-Hispanic White, Non-Hispanic Black, and Korean adolescents. The data were collected from datasets of the National Health and Nutrition Examination Survey between 1999 and 2012, and the Korean National Health and Nutrition Examination Survey between 2005 and 2013. Receiver operating characteristic curve analysis was used to find valid cut-off values of the TyG index for metabolic syndrome. The total number of eligible participants was 3,164 in the US and 4,873 in Korea. The optimal cut-off value with the Cook et al. definition revealed 8.55 in Mexican American, 8.55 in Non-Hispanic White, 8.35 in Non-Hispanic Black, and 8.45 in Korean, respectively. The cut-off value with the de Ferranti et al. definition was 8.45, 8.45, 8.15, and 8.35, and the cut-off value with the International Diabetes Federation definition was 8.65, 8.65, 8.15, and 8.55, respectively. These findings may be clinically useful for evaluating insulin resistance for determining metabolic abnormalities in adolescents.
Glacier retreat is a major long-standing global issue; however, the ecological impacts of such retreats on marine organisms remain unanswered. Here, we examined changes to the polar benthic community ...structure of "diatoms" under current global warming in a recently retreated glacial area of Marian Cove, Antarctica. The environments and spatiotemporal assemblages of benthic diatoms surveyed in 2018-2019 significantly varied between the intertidal (tidal height of 2.5 m) and subtidal zone (10 and 30 m). A distinct floral distribution along the cove (~ 4.5 km) was characterized by the adaptive strategy of species present, with chain-forming species predominating near the glacier. The predominant chain-forming diatoms, such as Fragilaria striatula and Paralia sp., are widely distributed in the innermost cove over years, indicating sensitive responses of benthic species to the fast-evolving polar environment. The site-specific and substrate-dependent distributions of certain indicator species (e.g., F. striatula, Navicula glaciei, Cocconeis cf. pinnata) generally reflected such shifts in the benthic community. Our review revealed that the inner glacier region reflected trophic association, featured with higher diversity, abundance, and biomass of benthic diatoms and macrofauna. Overall, the polar benthic community shift observed along the cove generally represented changing environmental conditions, (in)directly linked to ice-melting due to the recent glacier retreat.
Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the ...expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 95% CI, 0.425-0.953;
=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits.
The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.
Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There ...seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.
Ultrafast carrier dynamics in a graphene system are very important in terms of optoelectronic devices. Recently, a twisted bilayer graphene has been discovered that possesses interesting electronic ...properties owing to strong modifications in interlayer couplings. Thus, a better understanding of ultrafast carrier dynamics in a twisted bilayer graphene is highly desired. Here, we reveal the unbalanced electron distributions in a quasicrystalline 30° twisted bilayer graphene (QCTBG), using time- and angle-resolved photoemission spectroscopy on the femtosecond time scale. We distinguish time-dependent electronic behavior between the upper- and lower-layer Dirac cones and gain insight into the dynamical properties of replica bands, which show characteristic signatures due to Umklapp scatterings. The experimental results are reproduced by solving a set of rate equations among the graphene layers and substrate. We find that the substrate buffer layer plays a key role in initial carrier injections to the upper and lower layers. Our results demonstrate that QCTBG can be a promising element for future devices.
Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture ...conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.
We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460.
Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 62·8% of 137 in control, 79 57·2% of 138 in the linezolid 2 weeks group, and 75 62·0% of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient.
Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis.
Ministry of Health and Welfare, South Korea.
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