Cerebrovascular disease is a potential risk factor for Alzheimer's disease (AD). Although acute cerebral hypoperfusion causes neuronal necrosis and infarction, chronic cerebral hypoperfusion induces ...apoptosis in neurons, but its effects on the cognitive impairment are not clear. The purpose of this study was to evaluate the effects of chronic cerebral hypoperfusion on AD pathology and cerebral glucose metabolism. A model of chronic cerebral hypoperfusion was established by ligating the common carotid arteries bilaterally in adult male rats (CAL group). Sham-operated rats underwent the same procedures without artery ligation (control group). At 12 weeks after ligation, expression levels of amyloid-β (Aβ) and hyperphosphorylated tau (p-tau), as well as the regional cerebral glucose metabolism, were evaluated using Western blots and positron emission tomography with fluorine-18 fluorodeoxyglucose, respectively. The expression levels of Aβ in the frontal cortex and hippocampus and of p-tau in the temporal cortex were significantly higher in the CAL group than those in the control group. The cerebral glucose metabolism of the amygdala, entorhinal cortex, and hippocampus was significantly decreased in the CAL group compared to that in the control. These results suggest that chronic cerebral hypoperfusion can induce AD pathology and may play a significant role in AD development.
Currently, most commercial polyols used in the production of polyurethane (PU) foam are derived from petrochemicals. To address concerns relating to environmental pollution, a sustainable resource, ...namely, castor oil (CO), was used in this study. To improve the production efficiency, sustainability, and compressive strength of PU foam, which is widely used as an impact-absorbing material for protective equipment, PU foam was synthesized with CO-based multifunctional polyols. CO-based polyols with high functionalities were synthesized via a facile thiol-ene click reaction method and their chemical structures were analyzed. Subsequently, a series of polyol blends of castor oil and two kinds of castor oil-based polyols with different hydroxyl values was prepared and the viscosity of the blends was analyzed. Polyurethane foams were fabricated from the polyol blends via a free-rising method. The effects of the composition of the polyol blends on the structural, morphological, mechanical, and thermal properties of the polyurethane foams were investigated. The results demonstrated that the fabrication of polyurethane foams from multifunctional polyol blends is an effective way to improve their compressive properties. We expect these findings to widen the range of applications of bio-based polyurethane foams.
Summary Background Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine ...hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. Methods Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens–Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. Results Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients ( P = 0.011, Pc = not significant; OR = 18.0(2.3–141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls ( Pc = 0.011, OR = 8.8(2.5–30.7) and Pc = 0.013, OR = 7.3(2.3–22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. Conclusions HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.
Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ...ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte antigen (HLA) class I alleles of 25 cases of allopurinol-induced SCARs (20 cases of drug-induced hypersensitivity syndrome and five cases of Stevens-Johnson syndrome/toxic epidermal necrolysis) and 57 patients tolerant to allopurinol. Frequencies of B*5801 92.0 vs. 10.5%, P(c)=2.45×10(-11), odds ratio (OR)=97.8, Cw*0302 (92.0 vs. 12.3%, P(c)=9.39×10(-11), OR=82.1), and A*3303 (88.0 vs. 26.3%, P(c)=3.31×10(-6), OR=20.5) were significantly higher in SCARs compared with tolerant controls. In contrast, A*0201 was not found in SCARs patients despite relatively high frequency in tolerant controls (29.8%). We found strong positive association of HLA-B*5801 and negative association of HLA-A*0201 with the development of allopurinol-induced SCARs in the Korean population.
Cellular antioxidant enzymes play crucial roles in aerobic organisms by eliminating detrimental oxidants and maintaining the intracellular redox homeostasis. Therefore, the function of antioxidant ...enzymes is inextricably linked to the redox-dependent activities of multiple proteins and signaling pathways. Here, we report that the VEGFR2 RTK has an oxidation-sensitive cysteine residue whose reduced state is preserved specifically by peroxiredoxin II (PrxII) in vascular endothelial cells. In the absence of PrxII, the cellular H2O2 level is markedly increased and the VEGFR2 becomes inactive, no longer responding to VEGF stimulation. Such VEGFR2 inactivation is due to the formation of intramolecular disulfide linkage between Cys1199 and Cys1206 in the C-terminal tail. Interestingly, the PrxII-mediated VEGFR2 protection is achieved by association of two proteins in the caveolae. Furthermore, PrxII deficiency suppresses tumor angiogenesis in vivo. This study thus demonstrates a physiological function of PrxII as the residential antioxidant safeguard specific to the redox-sensitive VEGFR2.
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► PrxII specifically prevents the oxidative inactivation of VEGFR2 in ECs ► VEGFR2 oxidation involves the formation of cysteine disulfide in C-terminal tail ► PrxII-dependent protection of VEGFR2 against oxidation is valid within caveolae ► Deficiency of PrxII retards tumor growth by inhibiting angiogenesis in vivo
Assessing advertisements, specifically on the basis of user preferences and ad quality, is crucial to the marketing industry. Although recent studies have attempted to use deep neural networks for ...this purpose, these studies have not utilized image-related auxiliary attributes, which include embedded text frequently found in ad images. We, therefore, investigated the influence of these attributes on ad image preferences. First, we analyzed large-scale real-world ad log data and, based on our findings, proposed a novel multi-step modality fusion network (M2FN) that determines advertising images likely to appeal to user preferences. Our method utilizes auxiliary attributes through multiple steps in the network, which include conditional batch normalization-based low-level fusion and attention-based high-level fusion. We verified M2FN on the AVA dataset, which is widely used for aesthetic image assessment, and then demonstrated that M2FN can achieve state-of-the-art performance in preference prediction using a real-world ad dataset with rich auxiliary attributes.
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•We propose a novel deep neural networks model for advertisement image assessment.•It fuses modalities via conditional batch normalization and an attention mechanism.•We leverage visual--linguistic attributes along with classic metadata.•We show state-of-the-art results for aesthetic and advertisement image assessment.•We show the results of ablation studies and visualization to support our claims.
Background. Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent ...investigations suggest that HLA-B*5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B*5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population.
Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity.
Methods. We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010.
Results. Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 18% in HLA-B58 (+) versus 0% in HLA-B58 (−). Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol.
Conclusions. In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.
In melanoma, transition to the vertical growth phase is the critical step in conversion to a deadly malignant disease. Here, we offer the first evidence that an antioxidant enzyme has a key role in ...this transition. We found that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells. Silencing Prx2 expression stimulated proliferation and migration, whereas ectopic expression of Prx2 produced the opposite effect. Mechanistic investigations indicated that Prx2 negatively regulated Src/ERK activation status, which in turn fortified adherens junctions function by increasing E-cadherin expression and phospho-Y654-dependent retention of β-catenin in the plasma membrane. In murine melanoma cells, Prx2 silencing enhanced lung metastasis in vivo. Interestingly, the natural compound gliotoxin, which is known to exert a Prx-like activity, inhibited proliferation and migration as well as lung metastasis of Prx2-deficient melanoma cells. Overall, our findings reveal that Prx2 is a key regulator of invasion and metastasis in melanoma, and also suggest a pharmacologic strategy to effectively decrease deadly malignant forms of this disease.
This study aimed to investigate consumers’ intentions to purchase sustainable masks to reduce the environmental pollution caused by disposable masks in the context of COVID-19. A research model was ...derived based on the Value-Belief-Norm theory and the Theory of Planned Behavior, and the moderating role of health concerns and environmental knowledge due to the COVID-19 pandemic were examined. Through a Korean online survey company, we collected data on sustainable masks from respondents aged from their 20 s to 50 s, living in the Korea, and a structural equation analysis was performed on the 337 valid samples. Environmental concerns and beliefs were found to have a positive impact on the purchase intention on sustainable masks. Although environmental knowledge played the role of a moderator, we found that the higher the health concern, the stronger the purchase intention. Based on these results, it is possible to derive a strategy to increase the purchase of sustainable masks and reduce the environmental pollution caused by disposable masks. A sales strategy should be implemented for groups with high health concern. In addition, since the subjective norm increases the purchase intention for sustainable masks, advertising that stimulates them will help reduce environmental pollution caused by disposal masks. In the future, it will be possible to help reduce environmental pollution not only during the COVID-19 pandemic, but also during other emerging pandemics.
We present polymer nanocomposites of tungsten bronze nanorods (TBNRs) and ethylene propylene diene monomers (EPDM). The combination of these components allows the simultaneous enhancement in the ...mechanical and photothermal properties of the composites at low filler contents. The as-synthesized TBNRs had lengths and diameters of 14.0 ± 2.4 nm and 2.5 ± 0.5 nm, respectively, and were capped with oleylamine, which has a chemical structure similar to EPDM, making the TBNRs compatible with the bulk EPDM matrix. The TBNRs absorb a wide range of near-infrared light because of the sub-band transitions induced by alkali metal doping. Thus, the nanocomposites of TBNRs in EPDM showed enhanced photothermal properties owing to the light absorption and subsequent heat emission by the TBNRs. Noticeably, the nanocomposite with only 3 wt% TBNRs presented significantly enhanced tensile strain at break, in comparison with those of pristine EPDM, nanocomposites with 1 and 2 wt % TBNRs, and those with tungsten bronze nanoparticles, because of the alignment of the nanorods during tensile elongation. The photothermal and mechanical properties of these nanocomposites make them promising materials for various applications such as in fibers, foams, clothes with cold weather resistance, patches or mask-like films for efficient transdermal delivery upon heat generation, and photoresponsive surfaces for droplet transport by the thermocapillary effect in microfluidic devices and microengines.
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