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The indoor environment, particularly indoor air quality (IAQ), is significantly associated with building-related symptoms (BRSs) in humans. In our previous studies, we demonstrated a significant relationship between BRSs and indoor chemical concentrations. In Japan, the Ministry of Health, Labor, and Welfare (MHLW) guideline recommends an air quality target of 13 volatile organic compounds (VOCs) and a provisional target of 400 μg/m3 for total VOCs (TVOC). The objective of this study was to determine the relationship between TVOC levels and the risk of BRSs using the Japanese provisional target TVOC level of 400 μg/m3. The relationship between odor intensity and BRSs while the TVOC levels were under 400 μg/m3 was also examined. The study was conducted in a laboratory house (LH) on the campus of Chiba University from 2017-2019. The study included 149 participants who spent 60 minutes in the LH. The participants were asked to evaluate the IAQ of the LH. A significant relationship between the risk of BRSs and the provisional target TVOC level was observed (odds ratio: 2.94, 95% confidence interval: 1.18-7.35). Furthermore, a significant relationship between odor intensity and risk of BRSs in spaces with TVOC levels less than 400 μg/m3 was detected (odds ratio: 6.06, 95% confidence interval: 1.21-30.44). In conclusion, the risk of BRSs is significantly lower in spaces with low TVOC levels and low odor intensity. Reducing the concentration of airborne chemicals and odor intensity may improve IAQ and prevent BRSs.

Our recent success in the long-term maintenance of lantern shark embryos in artificial uterine systems has provided a novel option for the medical treatment of premature embryos for captive viviparous elasmobranchs. The remaining issue with this system is that the embryos cannot survive the abrupt change in the chemical environment from artificial uterine fluid (AUF) to seawater during delivery. To overcome this issue, the present study developed a new protocol for seawater adaptation, which is characterized by a long-term and stepwise shift from AUF to seawater prior to delivery. This protocol was employed successfully, and the specimen survived for more than seven months after delivery, the longest captive record of the species. During the experiment, we unexpectedly detected bioluminescence of the embryonic lantern shark in the artificial uterus. This observation indicates that lantern sharks can produce luciferin, a substance for bioluminescence. This contradicts the recent hypothesis that lantern sharks lack the ability to produce luciferin and use luciferin obtained from food sources.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is transmitted mainly by droplet or aerosol infection; however, it may also be transmitted by contact infection. SARS-CoV-2 that adheres to environmental surfaces remains infectious for several days. We herein attempted to inactivate SARS-CoV-2 and influenza A virus adhering to an environmental surface by dry fogging hypochlorous acid solution and hydrogen peroxide solution. SARS-CoV-2 and influenza virus were air-dried on plastic plates and placed into a test chamber for inactivation by the dry fogging of these disinfectants. The results obtained showed that the dry fogging of hypochlorous acid solution and hydrogen peroxide solution inactivated SARS-CoV-2 and influenza A virus in CT value (the product of the disinfectant concentration and contact time)-dependent manners. SARS-CoV-2 was more resistant to the virucidal effects of aerosolized hypochlorous acid solution and hydrogen peroxide solution than influenza A virus; therefore, higher concentrations of disinfectants or longer contact times were required to inactivate SARS-CoV-2 than influenza A virus. The present results provide important information for the development of a strategy that inactivates SARS-CoV-2 and influenza A virus on environmental surfaces by spatial fogging.

PurposeThe association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population.MethodsWe used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35-69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined.ResultsDuring an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04-2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78-1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P ConclusionMetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.

ObjectiveThe oxygen concentration within cancer tissue is known to be low, but is expected to increase rapidly when oxygen is supplied by angiogenesis and hematogenous metastasis, suggesting that rapid increases in oxygen levels might influence cancer cell physiology. Therefore, we investigated the effects of oxygen concentration fluctuations on the glucose metabolism of cancer cells.MethodsThe glucose metabolism of oral squamous cell carcinoma (HSC-2 and HSC-3) and normal epithelial (HaCaT) cells cultured under normoxic (21% oxygen) or hypoxic (1% oxygen) conditions was measured using a pH-stat system under normoxic or hypoxic conditions. The acidic end-products and reactive oxygen species (ROS) generated by glucose metabolism were also measured.ResultsUnder normoxic conditions, the metabolic activity of hypoxically cultured cancer cells was significantly increased, and the production of acids other than lactate was upregulated, while the normal cells did not respond to rapid increases in oxygen levels. ROS production was higher in normoxic conditions in all cells, especially the hypoxically cultured HSC-3 cells.ConclusionsRapid increases in oxygen levels might enhance the glucose metabolism of hypoxically cultured cancer cells by mainly activating the TCA cycle and electron transport system, which might activate cancer cells through the ATP and ROS generation.

Objective The oxygen concentration within cancer tissue is known to be low, but is expected to increase rapidly when oxygen is supplied by angiogenesis and hematogenous metastasis, suggesting that rapid increases in oxygen levels might influence cancer cell physiology. Therefore, we investigated the effects of oxygen concentration fluctuations on the glucose metabolism of cancer cells. Methods The glucose metabolism of oral squamous cell carcinoma (HSC-2 and HSC-3) and normal epithelial (HaCaT) cells cultured under normoxic (21% oxygen) or hypoxic (1% oxygen) conditions was measured using a pH-stat system under normoxic or hypoxic conditions. The acidic end-products and reactive oxygen species (ROS) generated by glucose metabolism were also measured. Results Under normoxic conditions, the metabolic activity of hypoxically cultured cancer cells was significantly increased, and the production of acids other than lactate was upregulated, while the normal cells did not respond to rapid increases in oxygen levels. ROS production was higher in normoxic conditions in all cells, especially the hypoxically cultured HSC-3 cells. Conclusions Rapid increases in oxygen levels might enhance the glucose metabolism of hypoxically cultured cancer cells by mainly activating the TCA cycle and electron transport system, which might activate cancer cells through the ATP and ROS generation.

Despite its five meters length, the megamouth shark (Megachasma pelagios Taylor, Compagno & Struhsaker, 1983) is one of the rarest big sharks known in the world (117 specimens observed and documented so far). This filter-feeding shark has been assumed to be a luminous species, using its species-specific white band to produce bioluminescence as a lure trap. Another hypothesis was the use of the white band reflectivity to attract prey or for social recognition purposes. However, no histological study has ever been performed to confirm these assumptions so far. Two hypotheses about the megamouth shark's luminescence arose: firstly, the light emission may be intrinsically or extrinsically produced by specific light organs (photophores) located either on the upper jaw white band or inside the mouth; secondly, the luminous appearance might be a consequence of the reflection of prey luminescence on the white band during feeding events. Aims of the study were to test these hypotheses by highlighting the potential presence of specific photophores responsible for bioluminescence and to reveal and analyze the presence of specialized light-reflective structures in and around the mouth of the shark. By using different histological approaches (histological sections, fluorescent in situ hybridization, scanning electron microscopy) and spectrophotometry, this study allows to unravel these hypotheses and strongly supports that the megamouth shark does not emit bioluminescence, but might rather reflect the light produced by bioluminescent planktonic preys, thanks to the denticles of the white band.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutation of the methyl-CpG-binding protein 2 (MECP2) gene. Although RTT has been associated with obesity, the underlying mechanism has not yet been elucidated. In this study, female heterozygous Mecp2-null mice (Mecp2+/- mice), a model of RTT, were fed a normal chow diet or high-fat diet (HFD), and the changes in molecular signaling pathways were investigated. Specifically, we examined the expression of genes related to the hypothalamus and dopamine reward circuitry, which represent a central network of feeding behavior control. In particular, dopamine reward circuitry has been shown to regulate hedonic feeding behavior, and its disruption is associated with HFD-related changes in palatability. The Mecp2+/- mice that were fed the normal chow showed normal body weight and food consumption, whereas those fed the HFD showed extreme obesity with hyperphagia, an increase of body fat mass, glucose intolerance, and insulin resistance compared with wild-type mice fed the HFD (WT-HFD mice). The main cause of obesity in Mecp2+/--HFD mice was a remarkable increase in calorie intake, with no difference in oxygen consumption or locomotor activity. Agouti-related peptide mRNA and protein levels were increased, whereas proopiomelanocortin mRNA and protein levels were reduced in Mecp2+/--HFD mice with hyperleptinemia, which play an essential role in appetite and satiety in the hypothalamus. The conditioned place preference test revealed that Mecp2+/- mice preferred the HFD. Tyrosine hydroxylase and dopamine transporter mRNA levels in the ventral tegmental area, and dopamine receptor and dopamine- and cAMP-regulated phosphoprotein mRNA levels in the nucleus accumbens were significantly lower in Mecp2+/--HFD mice than those of WT-HFD mice. Thus, HFD feeding induced dysregulation of food intake in the hypothalamus and dopamine reward circuitry, and accelerated the development of extreme obesity associated with addiction-like eating behavior in Mecp2+/- mice.

BACKGROUND AND AIM:Awareness of eosinophilic esophagitis (EoE) has gradually increased in Japan, therefore the characteristics of this disease in the Japanese patient population need to be elucidated. This study aimed to investigate the features of EoE in the Japanese population. METHODS:During a 2-year period, all gastrointestinal endoscopies were performed with maximum attention being paid to identify EoE through endoscopic findings. Clinical features and findings were analyzed among this population. RESULTS:Among a total of 8589 patients (general gastrointestinal endoscopy, performed for evaluation of symptoms or disease follow-up: 3669; medical check-up endoscopy, routinely performed in asymptomatic patients: 4920), 17 patients (0.20%) were diagnosed with esophageal eosinophilia (mean age ± standard deviation: 44±11.9 years; 1 female). Only 6 patients with esophageal eosinophilia were diagnosed by general gastrointestinal endoscopy; among them, 3 patients had dysphagia and 3 were asymptomatic. The remaining 11 patients were diagnosed by medical check-up endoscopy. All patients were treated with a proton pump inhibitor (PPI); 5 were diagnosed with EoE and 12 with PPI responsive esophageal eosinophilia. Chronological endoscopy analysis showed that EoE findings could be observed for a mean of 6.1 years prior to diagnosis, and the disease did not significantly progress in severity. CONCLUSIONS:Most Japanese patients with EoE have mild and slowly progressing disease, which can be diagnosed when close attention is paid to the endoscopic findings. Medical check-up endoscopy in Japan could be a great opportunity for the early diagnosis of EoE.

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification.A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated.The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p

AimsGlomerular insudative lesions are a pathological hallmark of diabetic nephropathy (DN). However, paratubular basement membrane insudative lesions (PTBMIL) have not attracted much attention, and the association between such lesions and the renal prognosis remains unclear.MethodsAmong 142 patients with biopsy-proven DN and type 2 diabetes encountered from 1998 to 2011, 136 patients were enrolled in this study. Patients were classified into 3 groups (Group 1: mild, Group 2: moderate, Group 3: severe) according to the extent of cortical and medullary PTBMIL. The endpoint was a decline of the estimated glomerular filtration rate (eGFR) by ≥ 40% from baseline or commencement of dialysis for end-stage renal disease. The Cox proportional hazard model was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint.ResultsDuring a median follow-up period of 1.8 years (IQR: 0.9-3.5), the endpoint occurred in 104 patients. Baseline mean eGFR was 43.9 ± 22.8 ml/min/1.73 m2, and 125 patients (92%) had overt proteinuria. After adjusting for known indicators of DN progression, the HR for the endpoint was 2.32 (95% CI: 1.20-4.51) in PTBMIL Group 2 and 3.12 (1.48-6.58) in PTBMIL Group 3 versus PTBMIL Group 1. Furthermore, adding the PTBMIL Group to a multivariate model including known promoters of DN progression improved prediction of the endpoint (c-index increased by 0.02 [95% CI: 0.00-0.04]).ConclusionsPTBMIL may be useful for predicting the renal prognosis of patients with biopsy-proven DN, but further investigation of these lesions in various stages of DN is needed.

Somatosensory evoked fields (SEFs) to electrical stimulation on the right and left sides of the lower lip were measured using magnetoencephalography and compared in the bilateral hemispheres of 31 healthy normal young and 29 healthy normal elderly subjects to evaluate age-related change in lip somatosensation. The initial peak of the response around 13 ms, designated as N13m, and the second peak of the response, designated as P21m, were investigated. The N13m response, which was detected in 22 of 62 hemispheres in young adults and 37 of 58 hemispheres in elderly adults, showed significantly prolonged latency and increased equivalent current dipole (ECD) moment in the elderly adults. The P21m response, which was detected in 56 of 62 hemispheres in young adults and in 52 of 58 hemispheres in elderly adults, showed longer peak latency in the elderly adults. No significant difference was found in the ECD moment for P21m, which suggests that aging affected the SEFs of the lip somatosensation, but the effects of aging on N13m and P21m differed. Prolonged latency and increased ECD moment of N13m might result from decreased peripheral conduction and increased cortical excitation system associated with aging. Therefore, the initial response component might be an objective parameter for investigating change in lip function with age.

Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP), the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8), which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems. Here, we present an optimized method for nCaP-mediated gene delivery using an octa-arginine (R8)-functionalized nCaP vector containing a marker or functional gene construct. nCaP particle size was between 220-580 nm in diameter and all R8-functionalized nCaPs carried a positive charge. R8 concentration significantly improved nCaP transfection efficiency with high cell compatibility in human mesenchymal stem cells (hMSC) and human osteoblasts (hOB) in particular, suggesting nCaPs as a good option for non-viral vector gene delivery. Furthermore, pre-treatment with different endocytosis inhibitors identified that the endocytic pathway differed among cell lines and functionalized nanoparticles, with amiloride increasing transfection efficiency of R8-functionalized nCaPs in hMSC and hOB.

Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO's suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT's endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO's improvement of obesity and glucose homeostasis can be attributed to increased iBAT thermogenic capacity and activation of BAT's endocrine functions.

BACKGROUND:Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations. METHODS:We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline). RESULTS:During a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01-1.67, per 10 mL/min/1.73 m2) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23-1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20-3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR

Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.

There have been no reports concerning the self-face perception in patients with anorexia nervosa (AN). The purpose of this study was to compare the neuronal correlates of viewing self-face images (i.e. images of familiar face) and stranger-face images (i.e. images of an unfamiliar face) in female adolescents with and without AN. We used near-infrared spectroscopy (NIRS) to measure hemodynamic responses while the participants viewed full-color photographs of self-face and stranger-face. Fifteen females with AN (mean age, 13.8 years) and 15 age- and intelligence quotient (IQ)-matched female controls without AN (mean age, 13.1 years) participated in the study. The responses to photographs were compared with the baseline activation (response to white uniform blank). In the AN group, the concentration of oxygenated hemoglobin (oxy-Hb) significantly increased in the right temporal area during the presentation of both the self-face and stranger-face images compared with the baseline level. In contrast, in the control group, the concentration of oxy-Hb significantly increased in the right temporal area only during the presentation of the self-face image. To our knowledge the present study is the first report to assess brain activities during self-face and stranger-face perception among female adolescents with AN. There were different patterns of brain activation in response to the sight of the self-face and stranger-face images in female adolescents with AN and controls.

With ever-growing aging population and demand for denture treatments, pressure-induced mucosa lesion and residual ridge resorption remain main sources of clinical complications. Conventional denture design and fabrication are challenged for its labor and experience intensity, urgently necessitating an automatic procedure. This study aims to develop a fully automatic procedure enabling shape optimization and additive manufacturing of removable partial dentures (RPD), to maximize the uniformity of contact pressure distribution on the mucosa, thereby reducing associated clinical complications. A 3D heterogeneous finite element (FE) model was constructed from CT scan, and the critical tissue of mucosa was modeled as a hyperelastic material from in vivo clinical data. A contact shape optimization algorithm was developed based on the bi-directional evolutionary structural optimization (BESO) technique. Both initial and optimized dentures were prototyped by 3D printing technology and evaluated with in vitro tests. Through the optimization, the peak contact pressure was reduced by 70%, and the uniformity was improved by 63%. In vitro tests verified the effectiveness of this procedure, and the hydrostatic pressure induced in the mucosa is well below clinical pressure-pain thresholds (PPT), potentially lessening risk of residual ridge resorption. This proposed computational optimization and additive fabrication procedure provides a novel method for fast denture design and adjustment at low cost, with quantitative guidelines and computer aided design and manufacturing (CAD/CAM) for a specific patient. The integration of digitalized modeling, computational optimization, and free-form fabrication enables more efficient clinical adaptation. The customized optimal denture design is expected to minimize pain/discomfort and potentially reduce long-term residual ridge resorption.

The bactericidal effect of hydroxyl radical (·OH) generated by combination of photolysis of hydrogen peroxide (H2O2) and sonolysis of water was examined under the condition in which the yield of ·OH increased additively when H2O2 aqueous solution was concomitantly irradiated with laser and ultrasound. The suspension of Staphylococcus aureus mixed with the different concentrations of H2O2 was irradiated simultaneously with a laser light (wavelength: 405 nm, irradiance: 46 and 91 mW/cm2) and ultrasound (power: 30 w, frequency: 1.65 MHz) at 20 ± 1°C of the water bulk temperature for 2 min. The combination of laser and ultrasound irradiation significantly reduced the viable bacterial count in comparison with the laser irradiation of H2O2 alone. By contrast, the ultrasound irradiation alone exerted almost no bactericidal effect. These results suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity was synergistic. A multi-way analysis of variance also revealed that the interaction of H2O2 concentration, laser power and ultrasound irradiation significantly affected the bactericidal activity. Since the result of oxidative DNA damage evaluation demonstrated that the combination of laser and ultrasound irradiation significantly induced oxidative damage of bacterial DNA in comparison with the laser irradiation of H2O2 alone, it was suggested that the combination effect of photolysis of H2O2 and sonolysis of water on bactericidal activity would be exerted via oxidative damage of cellular components such as DNA.

Respiration in fishes involves buccal pumping, which is characterized by the generation of nearly continuous water flow over the gills because of the rhythmic expansion/compression of the pharyngeal cavity. This mechanism is achieved by the functions of the vascular, skeletal, and muscular systems. However, the process by which the embryo establishes the mechanism remains a mystery. Morphological and kinematical observations on captive cloudy catsharks, Scyliorhinus torazame, have suggested that the embryo starts buccal pumping just before the respiratory slits open on the egg capsule. During the pre-opening period, the embryo acquires oxygen mainly via the external gill filaments. After slit opening, respiration of the embryo involves buccal pumping to pass water over the "internal gills." The onset of buccal pumping accompanies four morphological changes: (1) regression of the external gill filaments, (2) development of blood vessels within the "internal gills," (3) completion of the development of hyoid skeletal and muscular elements, and (4) development of the oral valve. A previous study showed that buccal pumping allows the embryo to actively regulate oxygen intake by changing the pumping frequency. Thus, establishment of buccal pumping in the egg capsule is probably important for embryo survival in the unstable oxygen environment of the egg capsule after slit opening.

A pvsB-vctA-irgA triple deletion mutant of Vibrio parahaemolyticus can utilize enterobactin under iron-limiting conditions by inducing a previously undescribed receptor, PeuA (VPA0150), in response to extracellular alkaline pH and enterobactin. In silico analyses revealed the existence of a two-component regulatory system operon, peuRS, immediately upstream of peuA, which constitutes an operon with the TonB2 system genes. Both the peuRS and peuA-tonB2 operons were found to be upregulated under iron-limiting conditions in a ferric uptake regulator (Fur)-dependent manner. The involvement of peuA and peuRS in enterobactin utilization was analyzed by complementation experiments using deletion mutants. Primer extension analysis indicated that, under iron-limiting conditions, the transcription of peuA was initiated from the +1 site at pH 7.0 and from both the +1 and +39 sites at pH 8.0 in the presence of enterobactin. The +39 transcript was absent from the peuRS deletion mutant. Secondary structure prediction of their 5'-untranslated regions suggested that translation initiation is blocked in the +1 transcript, but not in the +39 transcript. Consistent with this, in vitro translation analysis demonstrated that production of PeuA was determined only by the +39 transcript. These studies establish a novel gene regulation mechanism in which the two-component regulatory system PeuRS enhances expression of the alternative +39 transcript that possesses non-inhibitory structure, allowing the peuA expression to be regulated at the translation stage.

This is the first known report on the skeletal and muscular systems, and the skin histology, of the pectoral fin of the rare planktivorous megamouth shark Megachasma pelagios. The pectoral fin is characterized by three features: 1) a large number of segments in the radial cartilages; 2) highly elastic pectoral fin skin; and 3) a vertically-rotated hinge joint at the pectoral fin base. These features suggest that the pectoral fin of the megamouth shark is remarkably flexible and mobile, and that this flexibility and mobility enhance dynamic lift control, thus allowing for stable swimming at slow speeds. The flexibility and mobility of the megamouth shark pectoral fin contrasts with that of fast-swimming sharks, such as Isurus oxyrhinchus and Lamna ditropis, in which the pectoral fin is stiff and relatively immobile.

Miriplatin (MPT) is a novel platinum complex used in TACE that shows promise for the treatment of hepatocellular carcinoma (HCC). However, rapid washout has been reported in some cases. Therefore, various methods of administration with MPT have been attempted to increase its therapeutic efficacy. One hopeful method is balloon-occluded TACE (B-TACE), but the therapeutic efficacy of B-TACE with MPT has not been evaluated.To investigate the treatment outcomes and factors involved in local recurrence after B-TACE with MPT in HCC.This study included 51 patients (55 nodules) with HCC lesions equal or less than 5 cm in diameter who underwent B-TACE with MPT between January 2012 and June 2013. Local recurrence after B-TACE with MPT and factors associated with local recurrence were evaluated.The overall local recurrence rate was 11.1% at 6 months and 26.2% at 12 months. The local recurrence rate did differ significantly depending on CT values immediately after B-TACE with MPT. Multivariate analysis also showed that the CT value after B-TACE with MPT was the only factor related to local recurrence after B-TACE.B-TACE with MPT achieves relatively good local control of HCC. The plain CT value immediately after B-TACE with MPT is a predictive factor for local recurrence. In patients with unsatisfactory CT values, locoregional therapy or additional treatment is required.

Our previous study showed that exposing mouse fibroblasts to proanthocyanidin (PA) for only 1 min accelerated cell proliferation in a concentration-dependent manner. In this study, exposing human gingival fibroblasts (HGFs) to PA for 1 min similarly accelerated the proliferative response of the cells. Besides the accelerated proliferative response, PA showed a cytoprotective effect on HGFs exposed to harsh environmental conditions; short-term exposure of HGFs in the mitotic phase to pure water or physiological saline resulted in a lower recovery of viable cells. Pretreatment and concomitant treatment with PA improved the low recovery of cells exposed to pure water or physiological saline. In addition, HGFs exposed to PA for 1 min proliferated well even after being cultured in serum-free medium. In 100% confluent HGFs, being cultured in serum-free medium resulted in a high intracellular reactive oxygen species (ROS) level, but pretreatment with PA prevented the cells from increasing intracellular ROS. Thus, the results suggest that a short-term PA treatment exerts cytoprotective effects on HGFs exposed to harsh environmental conditions by improving the intracellular oxidative stress response.

Nickel, cobalt, and chromium are well known to be causal agents of allergic contact dermatitis. Palladium (Pd) can also cause allergic disease and exposure results from wide use of this metal in dental restorations and jewelry. Metal allergy is categorized as a delayed-type hypersensitivity, and metal-responsive T cell clones have been isolated from allergic patients. However, compared to nickel, little is known about the pathology of allergic disease mediated by Pd, and pathogenic T cells are poorly understood. To identify the pathogenic T cells that are responsible for onset of Pd allergy, we enriched metal-responsive lymphocytes by sequential adoptive transfer of involved lymph node cells. Here we show that sequential adoptive transfer gradually increased the incidence and the intensity of Pd allergy, and CD8⁺ T cells are responsible for the disease as CD8⁺ T cell-depleted mice and β2-microglobulin-deficient mice did not develop Pd allergy. In addition, we found that draining lymph node cells skewed toward CD8⁺ T cells in response to Pd challenge in 8th adoptive transferred recipient mice. The CD8⁺ T cells expressed NKG2D, a costimulatory molecule involved in the production of IFN-γ. NKG2D ligand was also induced in Pd-injected tissues. Furthermore, both NKG2D ligand-transgenic mice, where NKG2D is downmodulated, and IFN-γ-deficient mice showed impaired Pd allergy. Taken together, these results indicate that IFN-γ-producing NKG2D⁺ CD8⁺ T cells are responsible for Pd allergy and suggest that NKG2D is a potential therapeutic target for treatment of metal allergy.

The purpose of the present study was to evaluate the risk of inducing bacterial resistance to disinfection treatment with photolysis of H2O2 and comparing this with existing antibacterial agents. We tested seven antibacterial agents, including amoxicillin, cefepime hydrochloride, erythromycin, ofloxacin, clindamycin hydrochloride, ciprofloxacin hydrochloride, and minocycline hydrochloride, as positive controls for validation of the assay protocol. For all of the agents tested, at least one of the four bacterial species (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Streptococcus salivarius) was resistant to these agents by repeated exposure to subinhibitory concentrations of the agents up to 10 times. In contrast, antibacterial activity against any of the bacterial species tested (S. aureus, E. faecalis, E. coli, S. salivarius, Pseudomonas aeruginosa, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans) was not affected by repeated exposure to the disinfection treatment up to 40 times. This finding suggested that the risk of inducing bacterial resistance by disinfection treatment was low. The active ingredient of this disinfection treatment is hydroxyl radicals generated by photolysis of H2O2. Therefore, hydroxyl radicals interact with several cell structures and different metabolic pathways in microbial cells, probably resulting in a lack of development of bacterial resistance. In conclusion, disinfection treatment with photolysis of H2O2 appears to be a potential alternative for existing antimicrobial agents in terms of a low risk of inducing bacterial resistance.

In the present study, the bactericidal effect of photo-irradiated proanthocyanidin was evaluated in relation to reactive oxygen species formation. Staphylococcus aureus suspended in proanthocyanidin aqueous solution was irradiated with light from a laser at 405 nm. The bactericidal effect of photo-irradiated proanthocyanidin depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power. When proanthocyanidin was used at the concentration of 1 mg/mL, the laser irradiation of the bacterial suspension could kill the bacteria with a >5-log reduction of viable cell counts. By contrast, bactericidal effect was not observed when proanthocyanidin was not irradiated. In electron spin resonance analysis, reactive oxygen species, such as hydroxyl radicals, superoxide anion radicals, and hydrogen peroxide, were detected in the photo-irradiated proanthocyanidin aqueous solution. The yields of the reactive oxygen species also depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power as is the case with the bactericidal assay. Thus, it is indicated that the bactericidal effect of photo-irradiated proanthocyanidin is exerted via the reactive oxygen species formation. The bactericidal effect as well as the yield of the oxygen radicals increased with the concentration of proanthocyanidin up to 4 mg/mL, and then decreased with the concentration. These findings suggest that the antioxidative activity of proanthocyanidin might prevail against the radical generation potency of photo-irradiated proanthocyanidin resulting in the decreased bactericidal effect when the concentration is over 4 mg/mL. The present study suggests that photo-irradiated proanthocyanidin whenever used in an optimal concentration range can be a new disinfection technique.

BACKGROUND: Photodynamic therapy (PDT) has been suggested as an efficient clinical approach for the treatment of dental plaque in the field of dental care. In PDT, once the photosensitizer is irradiated with light of a specific wavelength, it transfers the excitation energy to molecular oxygen, which gives rise to singlet oxygen. METHODOLOGY/PRINCIPAL FINDINGS: Since plaque disclosing agents usually contain photosensitizers such as rose bengal, erythrosine, and phloxine, they could be used for PTD upon photoactivation. The aim of the present study is to compare the ability of these three photosensitizers to produce singlet oxygen in relation to their bactericidal activity. The generation rates of singlet oxygen determined by applying an electron spin resonance technique were in the order phloxine > erythrosine ≒ rose bengal. On the other hand, rose bengal showed the highest bactericidal activity against Streptococcus mutans, a major causative pathogen of caries, followed by erythrosine and phloxine, both of which showed activity similar to each other. One of the reasons for the discrepancy between the singlet oxygen generating ability and bactericidal activity was the incorporation efficiency of the photosensitizers into the bacterial cells. The incorporation rate of rose bengal was the highest among the three photosensitizers examined in the present study, likely leading to the highest bactericidal activity. Meanwhile, the addition of L-histidine, a singlet oxygen quencher, cancelled the bactericidal activity of any of the three photoactivated photosensitizers, proving that singlet oxygen was responsible for the bactericidal action. CONCLUSIONS: It is strongly suggested that rose bengal is a suitable photosensitizer for the plaque disclosing agents as compared to the other two photosensitizers, phloxine and erythrosine, when used for PDT.