Polycyclic aromatic hydrocarbons in urban particle matter exacerbate movement disorder after ischemic stroke via potentiation of neuroinflammation.

BACKGROUND: A recent epidemiological study showed that air pollution is closely involved in the prognosis of ischemic stroke. We and others have reported that microglial activation in ischemic stroke plays an important role in neuronal damage. In this study, we investigated the effects of urban aerosol exposure on neuroinflammation and the prognosis of ischemic stroke using a mouse photothrombotic model. RESULTS: When mice were intranasally exposed to CRM28, urban aerosols collected in Beijing, China, for 7 days, microglial activation was observed in the olfactory bulb and cerebral cortex. Mice exposed to CRM28 showed increased microglial activity and exacerbation of movement disorder after ischemic stroke induction. Administration of core particles stripped of attached chemicals from CRM28 by washing showed less microglial activation and suppression of movement disorder compared with CRM28-treated groups. CRM28 exposure did not affect the prognosis of ischemic stroke in null mice for aryl hydrocarbon receptor, a polycyclic aromatic hydrocarbon (PAH) receptor. Exposure to PM2.5 collected at Yokohama, Japan also exacerbated movement disorder after ischemic stroke. CONCLUSION: Particle matter in the air is involved in neuroinflammation and aggravation of the prognosis of ischemic stroke; furthermore, PAHs in the particle matter could be responsible for the prognosis exacerbation.

Butyrate Enhances γ-H2AX Induced by Benzo[a]pyrene.

Benzo[a]pyrene (BaP) is known to form DNA adduct following metabolic activation, which causes phosphorylation of histone H2AX (γ-H2AX). Recent studies have shown that histone deacetylase (HDAC) inhibitors enhanced BaP-induced CYP1A1 gene expression. In this study, we examined the relationship between the HDAC inhibitor-augmented metabolic activation and BaP-induced γ-H2AX. Sodium butyrate (SB), a typical HDAC inhibitor, enhanced BaP-induced γ-H2AX. The enhanced DNA damage was further confirmed by biased sinusoidal field gel electrophoresis, which detects DNA double-strand breaks. SB remarkably augmented BaP-induced CYP1A1 gene expression, and CYP1A1-overexpressing cells showed elevated generation of γ-H2AX. Furthermore, SB enhanced intracellular oxidation after treatment with BaP. These results suggested that SB-induced CYP1A1 upregulation facilitated BaP metabolism, which might result in excess DNA adducts or oxidative DNA damages, leading to augmentation of γ-H2AX.

Efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen for prevention of seizure recurrence during the same fever episode in children with suspected simple febrile seizures.

OBJECTIVE: This study was undertaken to evaluate the efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen in comparison with as-needed acetaminophen alone for prevention of seizure recurrence during the same fever episode in suspected pediatric simple febrile seizures (SFS). METHODS: This single-center, prospective, observational study was conducted from July 29, 2019 to February 15, 2021 at a children's hospital. Children aged 6 months to 60 months presenting to the emergency department with suspected SFS were included. Participants receiving both diazepam suppositories and as-needed acetaminophen were compared with those receiving as-needed acetaminophen alone. The primary outcome was seizure recurrence during the same fever episode. The secondary outcomes included the incidence of central nervous system (CNS) pathologies, adverse events, and medical costs. RESULTS: Of the 316 participants, 228 (72.2%) had their first febrile seizure. Diazepam (.3-.5 mg/kg for up to two doses) was administered to 88 of 316 patients (27.8%). The outcomes were available for 306 patients. The recurrence rate was 3.5% (3/85) in the patients receiving diazepam with as-needed acetaminophen and 12.2% (27/221) in the patients receiving as-needed acetaminophen alone (relative risk = .29, 95% confidence interval [CI] = .09-.93, p = .03). The adjusted odds ratio of diazepam administration against recurrence was .23 (95% CI = .07-.78, p = .02). None of the patients had a CNS pathology. No severe adverse events occurred, although mild ataxia was observed significantly more often in the patients receiving diazepam and as-needed acetaminophen (29.4% vs. 18.7%, p = .04). The median medical cost was US $199 (interquartile range [IQR] = 86-244) for the group receiving both medications and US $202 (IQR = 114-242) for the group receiving as-needed acetaminophen alone. SIGNIFICANCE: Compared with as-needed acetaminophen alone, diazepam with as-needed acetaminophen may reduce seizure recurrence more during the same fever episode without severe adverse events or additional costs in children with suspected SFS.

Pediatric acute dacryocystitis due to Eikenella corrodens: A case report.

Eikenella corrodens is a facultatively anaerobic gram-negative rod bacterium in the oropharynx and respiratory tract. It is a member of HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, E. corrodens, and Kingella kingae) group commonly associated with endocarditis and craniofacial infections. It is usually susceptible to penicillin, second and third-generation cephalosporins, and carbapenem, but has variable susceptibility to first-generation cephalosporin. We herein provide a description of the first case of pediatric acute dacryocystitis caused by E. corrodens. The patient did not respond to oral cephalexin and required surgical drainage followed by intravenous cefotaxime. Also provided is a brief review of the current literature.

Subjective Household Economic Status and Obesity in Toddlers: A Cross-Sectional Study of Daycare Centers in Japan.

BACKGROUND: Although lower household economic status is known to be a risk factor for obesity among school-age children, such an association among toddlers remains unclear. The present study investigated the association between household economic status and obesity in toddlers. DESIGN: We conducted a cross-sectional study of children aged 4 years attending daycare centers in Japan. Information on subjective household economic status ["affluent", "neither", "less affluent", or "non-affluent"] was collected via questionnaire from the children's guardians in 2015. Based on measured values of height and weight, obesity was defined using the International Obesity Task Force cut-offs of overweight (BMI ≥17.47 for boys and ≥17.19 for girls). We used the logistic regression model to investigate the association between household economic status and obesity. RESULTS: Among 1,848 respondents, the prevalence of obesity was 6.8%. Non-affluent household economic status was associated with a significantly higher probability of obesity in toddlers; the multivariate adjusted odds ratio for "non-affluent" households was 2.31 (95% confidence interval, 1.23-4.33) compared with "affluent" households. CONCLUSION: Perception of non-affluent economic status by the guardian was associated with a higher probability of toddler obesity. This result suggests that non-affluent household economic status is associated with obesity in toddlers.

Progression of vasogenic edema induced by activated microglia under permanent middle cerebral artery occlusion.

Brain edema is a severe complication that accompanies ischemic stroke. Increasing evidence shows that inflammatory cytokines impair tight junctions of the blood-brain barrier, suggesting the involvement of microglia in brain edema. In this study, we examined the role of microglia in the progression of ischemic brain edema using mice with permanent middle cerebral artery occlusion. The intensity of T2-weighted imaging (T2WI) in the cerebral cortex and the striatum was elevated 3 h after occlusion and spread to peripheral regions of the ischemic hemisphere. Merged images of 2,3,5-triphenyl tetrazolium chloride staining and T2WI revealed the exact vasogenic edema region, which spread from the ischemic core to outside the ischemic region. Microglia were strongly activated in the ischemic region 3 h after occlusion and, notably, activated microglia were observed in the non-ischemic region 24 h after occlusion. Pretreatment with minocycline, an inhibitor of microglial activation clearly suppressed not only vasogenic edema but also infarct formation. We demonstrated in this study that vasogenic edema spreads from the ischemic core to the peripheral region, which can be elicited, at least in part, by microglial activation induced by ischemia.

Sasa veitchii extract suppresses carbon tetrachloride-induced hepato- and nephrotoxicity in mice.

OBJECTIVE: The aim of this study was to investigate the therapeutic effects of a Sasa veitchii leaf extract (SE) on carbon tetrachloride (CCl4)-induced hepato- and nephrotoxicity. METHODS: Seven-week-old male ddy mice were orally administered SE or saline for seven days. Twenty-four hours after the last SE or saline administration, the mice were intraperitoneally injected with 3 g/kg CCl4 or olive oil. The mice from each group were euthanized and bled for plasma analysis 24 h after the CCl4/olive oil injection. RESULTS: We found that pretreatment with SE completely abolished the CCl4-induced mortality in the mice after 24 h. The mice pretreated with SE exhibited significantly decreased levels of functional markers, and reduced histological damage in both the liver and the kidney. Furthermore, we found that the SE pretreatment decreased lipid peroxidation and calcium levels in the liver. Although SE could not induce the free radical-scavenging metallothioneins, the plasma biological antioxidant power was significantly increased in the mice pretreated with SE. CONCLUSION: Our findings demonstrate that prophylactic treatment with SE protects mice from CCl4-induced lethal toxicity by decreasing oxidative stress in the liver and kidney, presumably by increasing biological antioxidant power.

Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents.

A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the ß-2,5-dihydropyrrolyl α,ß-unsaturated esters 5aa-5fc, which exhibit anticancer activity.

Synthesis of 2-aryl-3-trifluoromethylquinolines using (E)-trimethyl(3,3,3-trifluoroprop-1-enyl)silane.

The Hiyama cross-coupling reaction of (E)-trimethyl(3,3,3-trifluoroprop-1-enyl)silane (1) with 2-iodoaniline (2) proceeded without any protection of the amino group. The coordination of copper(II) fluoride to 2,2'-bipyridyl provided the fluoride source required to trigger this reaction, affording (E)-2-(3,3,3-trifluoroprop-1-enyl)aniline (3). In the presence of a stoichiometric amount of [Cu(OTf)]2·C6H6, the treatment of 3 with an aryl aldehyde at 200 °C provided the 2-aryl-3-trifluoromethylquinoline (4) via the oxidative cyclization of an in situ-generated imine substructure.

Association of Yersinia Infection With Kawasaki Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Yersinia infection is known to present with Kawasaki disease (KD)-like symptoms although differentiating the 2 has been a challenge. The present study aimed to describe the clinical characteristics and prevalence of Yersinia infection presenting with KD-like symptoms. METHODS: The present, prospective, multicenter study enrolled patients who received a diagnosis of KD between January 2021 and January 2022 at 2 hospitals in Tokyo. Stool samples were collected within 3 days of the start of KD treatment, and cultures were performed for Yersinia . Clinical history and symptoms suggestive of Yersinia infection were also evaluated. RESULTS: During the study period, 141 KD patients were screened and 117 patients with evaluable stool samples were registered. Only 1 patient was positive for Yersinia pseudotuberculosis , which was detected from both stool and blood cultures. The patient was refractory to KD treatment but improved after initiation of appropriate antibiotic therapy. CONCLUSIONS: Routine screening for Yersinia is not appropriate for patients with KD and should be limited to certain patients in high-risk areas and those who are refractory to the standard KD treatment.

Stability Modification of Dye-sensitized Solar Cells by Ruthenium Dyes Embedded on Eggshell Membranes.

Dye-sensitized solar cells (DSSCs) have been one of the most promising technologies to convert sunlight into electricity repeatedly based on the mechanism that dyes inject/accept electron into the metal oxides/from redox mediator. Specifically, N719 ([RuL2(NCS)2], L: 4,4'-dicarboxy-2,2'-bipyridine), immobilized on TiO2 through the interaction between its ligands (-COO- and -NCS) and the oxygen on the TiO2 surface, has been used as a conventional DSSC dye with high voltage. Nevertheless, -NCS ligands have been removed from Ru2+ in N719 due to UV irradiation and exchanged with H2O or OH- in electrolyte, resulting in voltage drop. In this work, we developed the first DSSC using the N719-adsorbed Eggshell (ESM)-TiO2 composite to maintain the immobilization of N719 on TiO2 through electrostatic interaction between the protein of ESM and N719. The DSSC using the composite maintained the voltage even after 12 h light irradiation, although the voltage of DSSC without ESM dropped drastically. It means that the ESM contributed to stable photovoltaic performances of DSSCs through the protection of NCS ligands of N719.

Assessment of Dye-Absorbed Eggshell Membrane Composites as Solid Polymer Electrolyte of Fuel Cells.

Recently, polymer electrolytes have been developed for high-performance and eco-friendly fuel cells. Among the candidates, eggshell membrane (ESM) has been promising because of its abundance to assemble various energy devices with low cost and its absorption ability of organic materials. In this work, we investigated fuel cells that included ESM-absorbing xanthene-, triphenylmethane-, and azo-type tar dye, which contained abundant hydrophilic groups, as polymer electrolytes. We found out two points: (1) that the fuel cells that included ESM-absorbing xanthene-type dye generated the highest I-V performance, and (2) the basic molecular structures of the tar dyes determined the correlation of the maximum power and proton conductivities.

Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes.

Lipid microdomains or caveolae, small invaginations of plasma membrane, have emerged as important elements for lipid uptake and glucose homeostasis. Sphingomyelin (SM) is one of the major phospholipids of the lipid microdomains. In this study, we investigated the physiological function of sphingomyelin synthase 2 (SMS2) using SMS2 knock-out mice, and we found that SMS2 deficiency prevents high fat diet-induced obesity and insulin resistance. Interestingly, in the liver of SMS2 knock-out mice, large and mature lipid droplets were scarcely observed. Treatment with siRNA for SMS2 also decreased the large lipid droplets in HepG2 cells. Additionally, the siRNA of SMS2 decreased the accumulation of triglyceride in liver of leptin-deficient (ob/ob) mice, strongly suggesting that SMS2 is involved in lipid droplet formation. Furthermore, we found that SMS2 exists in lipid microdomains and partially associates with the fatty acid transporter CD36/FAT and with caveolin 1, a scaffolding protein of caveolae. Because CD36/FAT and caveolin 1 exist in lipid microdomains and are coordinately involved in lipid droplet formation, SMS2 is implicated in the modulation of the SM in lipid microdomains, resulting in the regulation of CD36/FAT and caveolae. Here, we established new cell lines, in which we can completely distinguish SMS2 activity from SMS1 activity, and we demonstrated that SMS2 could convert ceramide produced in the outer leaflet of the plasma membrane into SM. Our findings demonstrate the novel and dynamic regulation of lipid microdomains via conformational changes in lipids on the plasma membrane by SMS2, which is responsible for obesity and type 2 diabetes.

A 50-kilodalton Cry2A peptide is lethal to Bombyx mori and Lymantria dispar.

The Cry2Aa3 gene was introduced into asporogenic Bacillus thuringiensis, and the synthesized protoxin killed Bombyx mori and Lymantria dispar larvae. Chymotrypsin hydrolyzed the linkages between 49Tyr/Val50 and 145Lys/Ser146 in the protoxin, and 50- and 58-kDa fragments were generated, respectively. Both peptides killed the larvae of both insects.

Assessment of Eggshell Membrane as a New Type of Proton-Conductive Membrane in Fuel Cells.

Polymer electrolyte membrane fuel cells have recently attracted considerable attention as sustainable and eco-friendly electricity generation devices from the viewpoint of carbon neutrality. This study focuses on new discoveries related to the application of eggshell membranes to polymer electrolytes in the development of cheaper, more eco-friendly fuel cells. We observed the electricity generation of the fuel cells using an eggshell membrane as a proton-conductive material and a general carbonic acid aqueous solution. This new fuel cell will contribute to the continued improvement of available fuel cells at lower costs.

A Detection Method of Operated Fake-Images Using Robust Hashing.

SNS providers are known to carry out the recompression and resizing of uploaded images, but most conventional methods for detecting fake images/tampered images are not robust enough against such operations. In this paper, we propose a novel method for detecting fake images, including distortion caused by image operations such as image compression and resizing. We select a robust hashing method, which retrieves images similar to a query image, for fake-image/tampered-image detection, and hash values extracted from both reference and query images are used to robustly detect fake-images for the first time. If there is an original hash code from a reference image for comparison, the proposed method can more robustly detect fake images than conventional methods. One of the practical applications of this method is to monitor images, including synthetic ones sold by a company. In experiments, the proposed fake-image detection is demonstrated to outperform state-of-the-art methods under the use of various datasets including fake images generated with GANs.

Involvement of the Microglial Aryl Hydrocarbon Receptor in Neuroinflammation and Vasogenic Edema after Ischemic Stroke.

Microglia are activated after ischemic stroke and induce neuroinflammation. The expression of the aryl hydrocarbon receptor (AhR) has recently been reported to elicit cytokine expression. We previously reported that microglial activation mediates ischemic edema progression. Thus, the purpose of this study was to examine the role of AhR in inflammation and edema after ischemia using a mouse middle cerebral artery occlusion (MCAO) model. MCAO upregulated AhR expression in microglia during ischemia. MCAO increased the expression of tumor necrosis factor α (TNFα) and then induced edema progression, and worsened the modified neurological severity scores, with these being suppressed by administration of an AhR antagonist, CH223191. In THP-1 macrophages, the NADPH oxidase (NOX) subunit p47phox was significantly increased by AhR ligands, especially under inflammatory conditions. Suppression of NOX activity by apocynin or elimination of superoxide by superoxide dismutase decreased TNFα expression, which was induced by the AhR ligand. AhR ligands also elicited p47phox expression in mouse primary microglia. Thus, p47phox may be important in oxidative stress and subsequent inflammation. In MCAO model mice, P47phox expression was upregulated in microglia by ischemia. Lipid peroxidation induced by MCAO was suppressed by CH223191. Taken together, these findings suggest that AhR in the microglia is involved in neuroinflammation and subsequent edema, after MCAO via p47phox expression upregulation and oxidative stress.

Synaptic scaffolding molecule alpha is a scaffold to mediate N-methyl-D-aspartate receptor-dependent RhoA activation in dendrites.

Synaptic scaffolding molecule (S-SCAM) interacts with a wide variety of molecules at excitatory and inhibitory synapses. It comprises three alternative splicing variants, S-SCAMalpha, -beta, and -gamma. We generated mutant mice lacking specifically S-SCAMalpha. S-SCAMalpha-deficient mice breathe and feed normally but die within 24 h after birth. Primary cultured hippocampal neurons from mutant mice have abnormally elongated dendritic spines. Exogenously expressed S-SCAMalpha corrects this abnormal morphology, while S-SCAMbeta and -gamma have no effect. Active RhoA decreases in cortical neurons from mutant mice. Constitutively active RhoA and ROCKII shift the length of dendritic spines toward the normal level, whereas ROCK inhibitor (Y27632) blocks the effect by S-SCAMalpha. S-SCAMalpha fails to correct the abnormal spine morphology under the treatment of N-methyl-d-aspartate (NMDA) receptor inhibitor (AP-5), Ca(2+)/calmodulin kinase inhibitor (KN-62), or tyrosine kinase inhibitor (PP2). NMDA treatment increases active RhoA in dendrites in wild-type hippocampal neurons, but not in mutant neurons. The ectopic expression of S-SCAMalpha, but not -beta, recovers the NMDA-responsive accumulation of active RhoA in dendrites. Phosphorylation of extracellular signal-regulated kinase 1/2 and Akt and calcium influx in response to NMDA are not impaired in mutant neurons. These data indicate that S-SCAMalpha is a scaffold required to activate RhoA protein in response to NMDA receptor signaling in dendrites.

Decolorization and treatment of Kokuto-shochu distillery wastewater by the combination treatment involving biodecolorization and biotreatment by Penicillium oxalicum d, physical decolorization by ozonation and treatment by activated sludge.

Kokuto-shochu is a traditional Japanese distilled liquor made from brown sugar. Kokuto-shochu distillery wastewater (KDW) contains high concentrations of organic compounds and brown pigments (called molasses pigments) which are hardly decolorized by general biological wastewater treatment. A fungus, Penicillium oxalicum d, which we isolated in a previous study, decolorizes 47% of the color from KDW without the addition of any nutrients. P. oxalicum d decolorizes KDW by absorbing the pigments into its mycelia. Here we describe a KDW treatment system that combines biodecolorization and biotreatment by P. oxalicum d with treatment by activated sludge and physical decolorization by ozonation. Adding HClO to suppress bacterial growth and replacing fresh seed sludge at regular intervals helped to maintain the dominance and decolorization ability of P. oxalicum d. In a laboratory-scale demonstration, 48 cycles (12 days) achieved a decolorization ratio of 90% and removed more than 97% of dissolved organic carbon (DOC), dissolved total nitrogen (DTN) and dissolved total phosphorus (DTP). A major feature of our system is that it uses only 6% of the water used in an activated sludge-ozonation system.