Ultra‐deep‐blue aggregation‐induced delayed fluorescence (AIDF) emitters (TB‐tCz and TB‐tPCz) bearing organoboron‐based cores as acceptors and 3,6‐substituted carbazoles as donors are presented. The ...thermally activated delayed fluorescence (TADF) properties of the two emitters are confirmed by theoretical calculations and time‐resolved photoluminescence experiments. TB‐tCz and TB‐tPCz exhibit fast reverse intersystem crossing rate constants owing to efficient spin–orbit coupling between the singlet and triplet states. When applied in solution‐processed organic light‐emitting diodes (OLEDs), the TB‐tCz‐ and TB‐tPCz‐based nondoped devices exhibit ultra‐deep‐blue emissions of 416–428 nm and high color purity owing to their narrow bandwidths of 42.2–44.4 nm, corresponding to the Commission International de l´Eclairage color coordinates of (x = 0.16–0.17, y = 0.05–0.06). They show a maximum external quantum efficiency (EQEmax) of 8.21% and 15.8%, respectively, exhibiting an unprecedented high performance in solution‐processed deep‐blue TADF‐OLEDs. Furthermore, both emitters exhibit excellent device performances (EQEmax = 14.1–15.9%) and color purity in solution‐processed doped OLEDs. The current study provides an AIDF emitter design strategy to implement high‐efficiency deep‐blue OLEDs in the future.
Ultra‐deep‐blue aggregation‐induced delayed fluorescence emitters (TB‐tCz and TB‐tPCz) bearing organoboron‐based core and carbazole derivatives are developed. Solution‐processed nondoped organic light‐emitting diodes (OLEDs) based on TB‐tPCz exhibit a record external quantum efficiency of 15.8% with Commission international de l'éclairage color coordinates of (0.16, 0.05). Furthermore, both emitters also exhibit excellent device performances in solution‐processed doped OLEDs.
The Korean government established an antimicrobial resistance (AMR) surveillance system, compatible with the Global AMR Surveillance System (GLASS): Kor-GLASS. We describe results from the first year ...of operation of the Kor-GLASS from May 2016 to April 2017, comprising all non-duplicated clinical isolates of major pathogens from blood
urine
faeces and urethral and cervical swabs from six sentinel hospitals. Antimicrobial susceptibility tests were carried out by disk diffusion, Etest, broth microdilution and agar dilution methods. Among 67,803 blood cultures, 3,523 target pathogens were recovered. The predominant bacterial species were
(n = 1,536),
(n = 597) and
(n = 584). From 57,477 urine cultures, 6,394
and 1,097
were recovered. Bloodstream infections in inpatients per 10,000 patient-days (10TPD) were highest for cefotaxime-resistant
with 2.1, followed by 1.6 for meticillin-resistant
, 1.1 for imipenem-resistant
, 0.8 for cefotaxime-resistant
and 0.4 for vancomycin-resistant
. Urinary tract infections in inpatients were 7.7 and 2.1 per 10TPD for cefotaxime-resistant
and
, respectively. Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. A bacterial bank and a database for the collections are under development.
To monitor national antimicrobial resistance (AMR), the Korea Global AMR Surveillance System (Kor-GLASS) was established. This study analyzed bloodstream infection (BSI) cases from Kor-GLASS phase I ...from January 2017 to December 2019. Nine non-duplicated Kor-GLASS target pathogens, including
,
,
,
,
,
,
,
spp., and
spp., were isolated from blood specimens from eight sentinel hospitals. Antimicrobial susceptibility testing, AMR genotyping, and strain typing were carried out. Among the 20,041 BSI cases, 15,171 cases were caused by one of the target pathogens, and 12,578 blood isolates were collected for the study. Half (1,059/2,134) of
isolates were resistant to cefoxitin, and 38.1% (333/873) of
isolates were resistant to vancomycin. Beta-lactamase-non-producing ampicillin-resistant and penicillin-resistant
isolates by disk diffusion method were identified, but the isolates were confirmed as ampicillin-susceptible by broth microdilution method. Among
, an increasing number of isolates carried the
gene, and the ertapenem resistance in 1.4% (30/2,110) of
isolates was mostly (23/30) conferred by
carbapenemases. A quarter (108/488) of
isolates were resistant to meropenem, and 30.5% (33/108) of those carried acquired carbapenemase genes. Over 90% (542/599) of
isolates were imipenem-resistant, and all except one harbored the
gene. Kor-GLASS provided comprehensive AMR surveillance data, and the defined molecular mechanisms of resistance helped us to better understand AMR epidemiology. Comparative analysis with other GLASS-enrolled countries is possible owing to the harmonized system provided by GLASS.
Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC ...class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1− cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.
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•SARS-CoV-2-specific CD8+ T cells are effector memory cells in convalescents•CCR7+CD45RA+ cells are increased among SARS-CoV-2-specific cells in the late phase•SARS-CoV-2-specific CD8+ T cells have fewer IFN-γ+ cells than flu-specific cells•PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional
T cell responses have been demonstrated in COVID-19 patients, but ex vivo phenotypes and functions of SARS-CoV-2-specific T cells remain unclear. Rha et al. examined SARS-CoV-2-specific CD8+ T cells in acute and convalescent COVID-19 patients using MHC class I multimers, finding that PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional.
The development of a high‐performance oxygen evolution reaction (OER) catalyst is pivotal for the practical realization of a water‐splitting system. Although an extensive search for OER catalysts has ...been performed in the past decades, cost‐effective catalysts remain elusive. Herein, an amorphous cobalt phyllosilicate (ACP) with layered crystalline motif prepared by a room‐temperature precipitation is introduced as a new OER catalyst; this material exhibits a remarkably low overpotential (η ≈ 367 mV for a current density of 10 mA cm−2). A structural investigation using X‐ray absorption spectroscopy reveals that the amorphous structure contains layered motifs similar to the structure of CoOOH, which is demonstrated to be responsible for the OER catalysis based on density functional theory calculations. However, the calculations also reveal that the local environment of the active site in the layered crystalline motif in the ACP is significantly modulated by the silicate, leading to a substantial reduction of η of the OER compared with that of CoOOH. This work proposes amorphous phyllosilicates as a new group of efficient OER catalysts and suggests that tuning of the catalytic activity by introducing redox‐inert groups may be a new unexplored avenue for the design of novel high‐performance catalysts.
The amorphous cobalt phyllosilicate introduced in this study exhibits the basic nature of a phyllosilicate as well as superior oxygen evolution reaction (OER) catalytic activity. Density functional theory calculations on the OER mechanism suggest that the silicate component aids in substantially reducing the η of the catalytic active sites by modulating the local structure.
This study aimed to examine the anti-diabetic effect of germinated waxy black rice (GWBR) using streptozotocin (STZ)-induced diabetic rats. In the diabetic rats, GWBR supplementation for 8 weeks ...reduced plasma blood glucose concentrations, improved glucose clearance and prevented diabetes-induced weight loss. Rats with STZ-induced diabetes who received GWBR supplementation exhibited decreased expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter (GLUT) 2 genes and proteins in the small intestine via decreases in hepatocyte nuclear factor (HNF)-1α, HNF-1β, and HNF-4α, transcriptional factors that are involved in the regulation of SGLT1 and GLUT2, compared with the rats with STZ-induced diabetes that did not receive GWBR supplements. GWBR supplementation also enhanced the expression of GLUT4 and the genes and proteins involved in GLUT4 translocation, such as insulin receptor (IR) and insulin receptor substrate 1 (IRS1), and increased the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB, Akt) proteins in skeletal muscle. GWBR further increased glycogen synthase (GS) 1 by decreasing glycogen synthase kinase (GSK)-3β in skeletal muscle. Interestingly, GWBR recovered STZ-impaired pancreatic β-cells, resulting in increased insulin synthesis and secretion. In addition, GWBR reduced serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, aspartate transferase and alanine transferase concentrations and increased high-density lipoprotein cholesterol concentrations. Taken together, these findings suggest that GWBR could be a candidate for improving the diabetic condition by regulating glucose uptake in the intestine and muscle and regulating the secretion of insulin from the pancreas.
Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA ...has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.
Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs ...must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.
Current pharmacological treatments for Parkinson’s disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible ...dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.
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•Reactive astrocytes in SNpc produce excessive GABA via MAO-B in animal models of PD•Aberrant tonic inhibition causes reduced DA production in neurons and motor deficits•Dormant neurons are rescued by MAO-B inhibition or optogenetic neuronal activation
Heo et al. report that astrocytic GABA-mediated aberrant tonic inhibition of DA neurons leads to a reduction in TH expression and dopamine production, causing dormant DA neurons and motor deficits. Blocking astrocytic GABA synthesis by MAO-B inhibition or optogenetic activation of dormant DA neurons reverses PD pathology.
Alzheimer's disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of ...hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5-trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1-42 (Aβ1-42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1-42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels.
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