Central visual field (CVF) loss has been linked to poorer vision-related quality of life in eyes with open-angle glaucoma (OAG) and can occur even in early-stage OAG eyes. The present study investigated whether the detection of choroidal microvasculature dropout (CMvD) during follow-up, which may be a sign of perfusion deficiency in the optic nerve head, is associated with rapid rate of CVF loss in early-stage OAG eyes. This study included 44 Korean OAG eyes with CMvD, identified by optical coherence tomography angiography, and 44 Korean OAG eyes without CMvD matched for age and severity of visual field loss at initial presentation. The rates of mean threshold changes in global and CVF were compared in eyes with and without CMvD using a linear mixed model. Clinical variables associated with rapid rate of CVF progression were also identified using a linear mixed model. The CVF progression rate was significantly higher in eyes with CMvD than in those without CMvD (-0.584 dB/year vs. -0.190 dB/year; P < 0.001) and detection of CMvD during follow-up was an independent predictor of rapid CVF progression rate. The presence of CMvD may aid in identification of high-risk patients who may show faster CVF progression and require more aggressive treatment.

Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population.

Identifying changes in serum metabolites before the occurrence of acute myocardial infarction (AMI) is an important approach for finding novel biomarkers of AMI.

Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not H2O2, in cancer cells undergoing necroptosis. TNF-α-induced mitochondrial superoxide anions production is strictly RIP3 expression-dependent. Unexpectedly, TNF-α stimulates NADPH oxidase (NOX), not mitochondrial energy metabolism, to activate superoxide production in the RIP3-positive cancer cells. In parallel, mitochondrial superoxide-metabolizing enzymes, such as manganese-superoxide dismutase (SOD2) and peroxiredoxin III, are not involved in the superoxide accumulation. Mitochondrial-targeted superoxide scavengers and a NOX inhibitor eliminate the accumulated superoxide without affecting TNF-α-induced necroptosis. Therefore, our study provides the first evidence that mitochondrial superoxide accumulation is a consequence of necroptosis.

An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time.

Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but their specific signaling role in cancer progression is poorly understood. Here we demonstrate that Prx type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase (PARP) tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival. In human colorectal cancer cells with APC mutations, PrxII depletion consistently reduces the β-catenin levels and the expression of β-catenin target genes. Essentially, PrxII depletion hampers the PARP-dependent Axin1 degradation through tankyrase inactivation. Direct binding of PrxII to tankyrase ARC4/5 domains seems to be crucial for protecting tankyrase from oxidative inactivation. Furthermore, a chemical compound targeting PrxII inhibits the expansion of APC-mutant colorectal cancer cells in vitro and in vivo tumor xenografts. Collectively, this study reveals a redox mechanism for regulating tankyrase activity and implicates PrxII as a targetable antioxidant enzyme in APC-mutation-positive colorectal cancer.2-Cys peroxiredoxin (Prx) enzymes are highly expressed in most cancers but how they promote cancer progression is unclear. Here the authors show that in colorectal cancers with APC mutation, PrxII binds to tankyrase and prevents its oxidative inactivation, thereby preventing Axin1-dependent degradation of ²b-catenin.

Central visual field (CVF) loss is important in maintaining vision-related quality of life in eyes with open-angle glaucoma (OAG). The present study investigated whether nasalized location of central retinal vessel trunk (CRVT) at baseline is associated with rapid rate of CVF loss in early-stage OAG eyes. This study included 76 OAG eyes with high nasalization CRVT [HNL] group and 75 OAG eyes with low nasalization CRVT [LNL] group matched for glaucoma severity at baseline that showed progressive visual field (VF) loss. The rates of mean threshold changes at various regions were compared in the two groups using a linear mixed model. Clinical variables associated with rapid rate of CVF progression were also identified using a linear mixed model. The rate of CVF loss in the central 10° was significantly higher in the HNL group than that in the LNL group (-0.452 dB/year vs. -0.291 dB/year, P < 0.001). The average and inferior hemi-macular ganglion cell inner plexiform layer (GCIPL) progression rates were significantly faster in the HNL group than in the LNL group (P < 0.05). Nasalized location of CRVT was an independent predictor of a more rapid VF loss in the central 10° region (P < 0.05).

Endothelial mechanotransduction by fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology through mechanosensors on the cell membrane. The coxsackievirus and adenovirus receptor (CAR) is not only a viral receptor but also a component of tight junctions and plays an important role in tissue homeostasis. Here, we demonstrate the expression, regulatory mechanism, and role of CAR in vascular endothelial cells (ECs) under FSS conditions. Disturbed flow increased, whereas unidirectional laminar shear stress (LSS) decreased, CAR expression in ECs through the Krüppel-like factor 2 (KLF2)/activator protein 1 (AP-1) axis. Deletion of CAR reduced the expression of proinflammatory genes and endothelial inflammation induced by disturbed flow via the suppression of NF-κB activation. Consistently, disturbed flow-induced atherosclerosis was reduced in EC-specific CAR KO mice. CAR was found to be involved in endothelial mechanotransduction through the regulation of platelet endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation. Our results demonstrate that endothelial CAR is regulated by FSS and that this regulated CAR acts as an important modulator of endothelial mechanotransduction by FSS.

Although the organic light-emitting diode (OLED) has been successfully commercialized, the development of deep-blue OLEDs with high efficiency and long lifetime remains a challenge. Here, a novel hyperfluorescent OLED that incorporates the Pt(II) complex (PtON7-dtb) as a phosphorescent sensitizer and a hydrocarbon-based and multiple resonance-based fluorophore as an emitter (TBPDP and ν-DABNA) in the device emissive layer (EML), is proposed. Such an EML system can promote efficient energy transfer from the triplet excited states of the sensitizer to the singlet excited states of the fluorophore, thus significantly improving the efficiency and lifetime of the device. As a result, a deep-blue hyperfluorescent OLED using a multiple resonance-based fluorophore (ν-DABNA) with Commission Internationale de L'Eclairage chromaticity coordinate y below 0.1 is demonstrated, which attains a narrow full width at half maximum of ≈17 nm, fourfold increased maximum current efficiency of 48.9 cd A-1 , and 19-fold improved half-lifetime of 253.8 h at 1000 cd m-2 compared to a conventional phosphorescent OLED. The findings can lead to better understanding of the hyperfluorescent OLEDs with high performance.

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment.

Background and Objectives: Cerebral ischemia is one of the major preoperative complications. Dexmedetomidine is a well-known sedative-hypnotic agent that has potential organ-protective effects. We examine the miRNAs associated with preconditioning effects of dexmedetomidine in cerebral ischemia. Materials and Methods: Transient infarcts were induced in mice via reperfusion after temporary occlusion of one side of the middle cerebral artery. A subset of these mice was exposed to dexmedetomidine prior to cerebral infarction and miRNA profiling of the whole brain was performed. We administered dexmedetomidine and miRNA-323-5p mimic/inhibitor to oxygen-glucose deprivation/reoxygenation astrocytes. Additionally, we administered miR-323-5p mimic and inhibitor to mice via intracerebroventricular injection 2 h prior to induction of middle cerebral artery occlusion. Results: The infarct volume was significantly lower in the dexmedetomidine-preconditioned mice. Analysis of brain samples revealed an increased expression of five miRNAs and decreased expression of three miRNAs in the dexmedetomidine-pretreated group. The viability of cells significantly increased and expression of miR-323-5p was attenuated in the dexmedetomidine-treated oxygen-glucose deprivation/reoxygenation groups. Transfection with anti-miR-323-5p contributed to increased astrocyte viability. When miRNA-323-5p was injected intraventricularly, infarct volume was significantly reduced when preconditioned with the miR-323-5p inhibitor compared with mimic and negative control. Conclusions: Dexmedetomidine has a protective effect against transient neuronal ischemia-reperfusion injury and eight specific miRNAs were profiled. Also, miRNA-323-5p downregulation has a cell protective effect under ischemic conditions both in vivo and in vitro. Our findings suggest the potential of the miR-323-5p inhibitor as a therapeutic agent against cerebral infarction.

Human exposure to carcinogenic volatile organic compounds (VOCs), such as benzene, from hand sanitizers is a topic of current concern. In light of the heavy use of hand sanitizers during the COVID-19 pandemic, determination of exposure to toxicants present in these products deserves attention. The US Food and Drug Administration (FDA) had set an interim limit for benzene in alcohol-based hand sanitizers at 2000 parts-per-billion (ppb). We determined the concentrations of and exposure to three VOCs namely, benzene, toluene and styrene, in 200 hand sanitizers using high-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC-HRMS). Benzene, toluene and styrene were found in 31%, 25% and 32%, respectively, of the samples analyzed at mean concentrations of 395 (range: 0.181-22,300), 164 (range: 0.074-20,700) and 61.3 ng/g (range: 0.082-4200 ng/g), respectively. Benzene was found at concentrations > 2000 ng/g (above the FDA interim limit) in 5% of the samples, representing 9 brands. The mean potential dermal exposure doses (DEDs) to benzene (children/teenagers: 34.6; adults: 24.7 ng/kg-bw/d) were higher than those for toluene (children/teenagers: 14.4; adults: 10.3 ng/kg-bw/d) and styrene (children/teenagers: 5.37; adults: 3.83 ng/kg-bw/d) in the 200 hand sanitizers analyzed. The estimated cancer risk from exposure to benzene in children/teenagers and adults from hand sanitizer use (at an estimated usage rate of 5 g/day) was greater than the one-in-a-million risk benchmark (1.0 × 10-6) for 10% and 9% of the samples, respectively. To the best of our knowledge, this is the first study to determine both the concentrations of and exposure risks to benzene, toluene and styrene present in hand sanitizers.

Organizations maintain social media accounts and upload posts to show their activities and communicate with the public, as individual users do. Thus, organizations' social media accounts can be examined from the same perspective of that of individual users' accounts, with personality being one of the perspectives. In line with previous studies that analyzed the personality of non-human objects such as products, stores, brands, and websites, this study analyzed the personality of Instagram accounts of public health organizations. It also extracted features at content and pixel levels from the photos uploaded on the organizations' accounts and examined how they were related to the personality traits of the accounts. The results suggested that the personality of public health organizations can be summarized as being high in openness and agreeableness but lower in extraversion and neuroticism. Openness and agreeableness were the personality traits associated the most with the content-level features, while extraversion and neuroticism were the ones associated the most with the pixel-level features. In addition, for each of the two traits associated the most with either the content- or pixel- level features, their associations tended to be in opposite directions with one another. The personality traits, except for neuroticism, were predicted from the photo features with an acceptable level of accuracy.

Burn-related injuries are devastating injuries with a high mortality rate that affect people of all ages worldwide. We assessed the effectiveness of plasma jet treatment in altering the expression of genes involved in wound healing in a prospective longitudinal observational animal study. Six male Sprague-Dawley rats weighing 350 g were used, and burn wounds were made by applying a preheated brass comb (100°C) to the back of the rats, resulting in 4 full-thickness burn wounds separated by 3 interspaces. A total of 18 burn wounds were induced on 3 rats. One side of the burn, on each rat received plasma treatment (plasma group), while the other side did not (control group). The interspaces were subjected to the plasma jet for 2 min per day until 7 days post-wounding. Plasma treatment significantly decreased the expression of proinflammatory cytokines. Furthermore, an increase in the expression of anti-inflammatory cytokines was observed in the plasma group. We showed that plasma jet treatment could improve burn wound healing by altering the expression of genes involved in the development of wound healing.

The prevalence of metabolic syndrome is increasing in Korea, particularly among young adults. This trend will increase the incidence of cardiovascular and metabolic diseases in the future. Therefore, it is imperative to detect and prevent metabolic abnormalities early in life. Here, we established a hospital-based biobank cohort to identify the most prevalent dysmetabolic phenotype. The aim of this report was to inform other researchers of our protocol and to share our data for future collaboration.

Glutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic H2O2, which is derived from mitochondria. At the molecular level, the absence of GPx1 led to the strengthened sequential activation of sustained JNK and caspase-8 expression. Two signaling mechanisms are involved in the GPx1-dependent regulation of the apoptosis pathway: (1) GPx1 regulates the level of cytosolic H2O2 that oxidizes the redox protein thioredoxin 1, blocking ASK1 activation, and (2) GPx1 interacts with TRAF2 and interferes with the formation of the active ASK1 complex. Inducible knockdown of GPx1 expression impaired the tumorigenic growth of MDA-MB-231 cells (>70% reduction, P = 0.0034) implanted in mice by promoting apoptosis in vivo. Overall, this study reveals the apoptosis-related signaling function of a GPx family enzyme highly conserved in aerobic organisms.

Obesity has been increasing in many regions of the world, including Europe, USA, and Korea. To manage obesity, we should consider it as a disease and apply therapeutic methods for its treatment. Molecular and therapeutic approaches for obesity management involve regulating biomolecules such as DNA, RNA, and protein in adipose-derived stem cells to prevent to be fat cells. Multiple factors are believed to play a role in fat differentiation, with one of the most effective factor is Ca2+. We recently reported that the electromagnetic perceptive gene (EPG) regulated intracellular Ca2+ levels under various electromagnetic fields. This study aimed to investigate whether EPG could serve as a therapeutic method against obesity. We confirmed that EPG serves as a modulator of Ca2+ levels in primary adipose cells, thereby regulating several genes such as CasR, PPARγ, GLU4, GAPDH during the adipogenesis. In addition, this study also identified EPG-mediated regulation of myogenesis that myocyte transcription factors (CasR, MyoG, MyoD, Myomaker) were changed in C2C12 cells and satellite cells. In vivo experiments carried out in this study confirmed that total weight/ fat/fat accumulation were decreased and lean mass was increased by EPG with magnetic field depending on age of mice. The EPG could serve as a potent therapeutic agent against obesity.

Doxorubicin is a typical anticancer drug that causes cardiomyopathy and heart failure (HF). The aim of our study was to investigate incidence, risk factors for doxorubicin-induced HF in Korean cancer patients and their survival rate, utilizing a nationwide population-based cohort.

There are abundant peroxiredoxin (Prx) enzymes, but an increase of cellular H2O2 level always happens in apoptotic cells. Here, we show that cellular H2O2 switches different apoptosis pathways depending on which type of Prx enzyme is absent. TNF-α-induced H2O2 burst preferentially activates the DNA damage-dependent apoptosis pathway in the absence of PrxI. By contrast, the same H2O2 burst stimulates the RIPK1-dependent apoptosis pathway in the absence of PrxII by inducing the destruction of cIAP1 in caveolar membrane. Specifically, H2O2 induces the oxidation of Cys308 residue in the cIAP1-BIR3 domain, which induces the dimerization-dependent E3 ligase activation. Thus, the reduction in cIAP level by the absence of PrxII triggers cell-autonomous apoptosis in cancer cells and tumors. Such differential functions of PrxI and PrxII are mediated by interaction with H2AX and cIAP1, respectively. Collectively, this study reveals the distinct switch roles of 2-Cys Prx isoforms in apoptosis signaling.

When conflicts occur during integration of visual and auditory information, one modality often dominates the other, but the underlying neural circuit mechanism remains unclear. Using auditory-visual discrimination tasks for head-fixed mice, we found that audition dominates vision in a process mediated by interaction between inputs from the primary visual (VC) and auditory (AC) cortices in the posterior parietal cortex (PTLp). Co-activation of the VC and AC suppresses VC-induced PTLp responses, leaving AC-induced responses. Furthermore, parvalbumin-positive (PV+) interneurons in the PTLp mainly receive AC inputs, and muscimol inactivation of the PTLp or optogenetic inhibition of its PV+ neurons abolishes auditory dominance in the resolution of cross-modal sensory conflicts without affecting either sensory perception. Conversely, optogenetic activation of PV+ neurons in the PTLp enhances the auditory dominance. Thus, our results demonstrate that AC input-specific feedforward inhibition of VC inputs in the PTLp is responsible for the auditory dominance during cross-modal integration.