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Objective: Repeated spaced sessions of repetitive transcranial magnetic stimulation (TMS) to the human primary motor cortex can lead to dose-dependent increases in motor cortical excitability. However, this has yet to be demonstrated in a defined cortical circuit. We aimed to examine the effects of repeated spaced cortical paired associative stimulation (cPAS) on excitability in the motor cortex., Methods: cPAS was delivered to the primary motor cortex (M1) and posterior parietal cortex (PPC) with two coils. In the multi-dose condition, three sessions of cPAS were delivered 50-min apart. The single-dose condition had one session of cPAS, followed by two sessions of a control cPAS protocol. Motor-evoked potentials were evaluated before and up to 40 min after each cPAS session as a measure of cortical excitability., Results: Compared to a single dose of cPAS, motor cortical excitability significantly increased after multi-dose cPAS. Increasing the number of cPAS sessions resulted in a cumulative, dose-dependent effect on excitability in the motor cortex, with each successive cPAS session leading to notable increases in potentiation., Conclusion: Repeated spaced cPAS sessions summate to increase motor cortical excitability induced by single cPAS., Significance: Repeated spaced cPAS could potentially restore abilities lost due to disorders like stroke., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Cerium dioxide nanoparticles (CeONPs) have been extensively applied in research for future energy development due to two common oxidation states on their surface. Considering that shape (aspect ratio) is a key determinant of NPs-induced toxicity, we compared the toxicity of hexagonal (H)- and rod-shaped (R)-CeONPs in mice. At 24 h after pharyngeal aspiration, both types of CeONPs recruited surrounding immune cells (monocytes and neutrophils) into the lung, and R-CeONPs induced a more severe pulmonary inflammatory response compared with H-CeONPs. To identify an indicator to predict pulmonary inflammatory responses at the cellular level, we also investigated their responses in alveolar macrophage cells. At 24 h after treatment, both types of CeONPs were mainly located within the vacuoles (partially, in the lysosome) in the cytoplasm. Mitochondrial damage, intracellular calcium accumulation, and increased NO production were observed in cells exposed to both types of CeONPs, ultimately resulting in a decrease in cell viability. More interestingly, both types of CeONPs formed multinucleated giant cells. Meanwhile, contrary to when suspended in deionized water, R-CeONPs were strongly aggregated with a negative charge in cell culture media, whereas H-CeONPs were relatively well-dispersed with a positive charge. R-CeONPs-induced lysosomal extension was also recovered by premix with negatively charged DNA, and even NPs suspended in cell culture media without cells were detected under the FACS system, suggesting interference by protein corona. Therefore, we suggest that shape (aspect ratio) is an important factor determining inhaled NPs-induced pathology and that the effect of the surface charge and protein corona should be carefully considered in interpreting results derived from in vitro tests. Furthermore, we propose that the relationship between the formation of multinucleated giant cells and the inflammatory response of inhaled CeONPs should be further studied., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eun-Jung Park reports was provided by The Ministry of Science and ICT., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Retinal pigment epithelium (RPE) damage is a major factor in age-related macular degeneration (AMD). The RPE in AMD shows mitochondrial dysfunction suggesting an association of AMD with mitochondrial function. Therefore, exogenous mitochondrial transplantation for restoring and replacing dysfunctional mitochondria may be an effective therapeutic strategy for AMD. Here, we investigated the effects of extrinsic mitochondrial transplantation on senescence-induced ARPE-19 cells. We demonstrated mitochondrial dysfunction in replicative senescence-induced ARPE-19 cells after repeated passage. Imbalanced mitophagy and mitochondrial dynamics resulted in increased mitochondrial numbers and elevated levels of mitochondrial and intracellular reactive oxygen species. Exogenous mitochondrial transplantation improved mitochondrial dysfunction and alleviated cellular senescence hallmarks, such as increased cell size, increased senescence-associated β-galactosidase activity, augmented NF-κB activity, increased inflammatory cytokines, and upregulated the cyclin-dependent kinase inhibitors p21 and p16. Further, cellular senescence properties were improved by exogenous mitochondrial transplantation in oxidative stress-induced senescent ARPE-19 cells. These results indicate that exogenous mitochondrial transplantation modulates cellular senescence and may be considered a novel therapeutic strategy for AMD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Machine vision techniques for monitoring heart rates in aquatic bioassays have been applied to cardiotoxicity assessment. However, the requisite large data sizes and long calculation times make long-term observations of heart rates difficult. In this study, we developed a real-time heart rate monitoring system for individual Daphnia magna in a water chamber mounter that immobilizes their movement in 100 mL media. Heart rates are calculated from real-time, time-resolved relative phase information from digital holograms acquired with a 200 fps camera and parallel computation using a graphics processing unit. With this system, we monitored the real-time changes in the heart rates of individual D. magna specimens exposed to H 2 O 2 as a positive control for reactive oxygen species (ROS) levels in an aquatic environment for 10 h, a period long enough to observe dynamic heart rate responses to the mounting process and exposure and to establish heart rate trends. An additional group analysis was conducted to compare to conventional cardiotoxicity assessment, with results of both assessments showing that the heart rates reduced according to ROS level by H 2 O 2 exposure concentration. Notably, the results of our real-time dynamic heart rate monitoring in aquatic conditions indicated that establishing a relaxation heart rate before measurements could improve the accuracy of toxicity assessment. It is believed that the system developed in this study, achieving the simultaneous measurement, analysis, and display of reconstructed results, will find wide application in other aquatic bioassays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Dry eye syndrome (DES) is a multifactorial condition characterized by insufficient tear lubrication and eye irritation. Air pollutants, including particulate matter (PM), are an emerging threat to human health causing DES and other diseases. However, the pathogenic mechanisms of DES induced by PM exposure remain to be fully elucidated. Recent studies have attempted to create DES animal model using PM exposure. In this study, we explored a novel in vivo exposure model of DES, utilizing an inhalation device (aerosol exposure system) to reproduce the natural exposure to atmospheric PM. Rats were exposed to urban PM (UPM) using this aerosol system for 5 h per day over 5 days. Tear volume in UPM-exposed rats decreased significantly, whereas corneal irregularity and lissamine green staining significantly increased following UPM exposure. Additional effects observed following UPM exposure included apoptosis in the corneal epithelium and a decrease in the number of goblet cells in the conjunctiva. UPM also affected the stability of the tear film by disrupting its mucin-4 layer. In conclusion, aerosol exposure systems have proven effective as assessment tools for DES caused by PM., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigated the removal of microplastics from different treatment stages in three WWTPs and examined the performance of tertiary treatment that was done by coagulation and different technologies such as ozone (WWTP-A), membrane disc-filter (WWTP-B), and rapid sand filtration (WWTP-C). The results showed that the primary and secondary treatment processes effectively remove microplastics from wastewater with efficiencies ranging between 75% and 91.9%. The removal efficiency increased further to >98% after tertiary treatment. Microbeads and fragments were the major types of microplastics found in all wastewater sampling points. Microbeads found in the wastewater samples were classified as primary microplastics, that mainly came from personal care products, whereas secondary microplastics consisted of fragments, fibers, and sheets that were generated mainly due to fragmentation of larger plastics. Microplastics were still found in a high concentration in the final effluent, especially from WWTP-B, which is discharged into the Geumho river., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Laparoscopic antireflux surgery is a standard surgical treatment method for gastroesophageal reflux disease (GERD) in Western countries. However, the procedure has not been actively carried out in Korea because of concerns regarding surgical complications. Here, we conducted this study to evaluate short-term surgical outcomes of laparoscopic Nissen fundoplication (LNF) performed at a single institution., Methods: From January 2010 to August 2016, totally 29 patients underwent LNF for GERD performed by three surgeons at Asan Medical Center, Korea. All patients participated in a telephonic survey including the presence of symptoms and the status of quality of life (QOL)., Results: The median age at operation and BMI were 54 years and 23.8 kg/m 2 , respectively. Preoperatively, 27 patients (93.1%) underwent PPI therapy. All patients had typical or atypical GERD symptoms. One patient (3.4%) required reoperation because of total gastroesophageal junction obstruction. 24 patients (82.8%) reported complete or partial resolution of symptoms, whereas 21 (72.4%) reported partial or complete improvement in quality of life. In patients with reflux esophagitis, GERD symptoms were significantly relieved after LNF (P = 0.005). LNF responders tended to perceive an improvement in quality of life post operation (P < 0.001)., Conclusion: LNF is a feasible, safe, and effective treatment option for controlling GERD symptoms as well as improving the quality of life. Presence of reflux esophagitis was a predictor of successful outcomes., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: Sacral neuromodulation is an effective therapy for overactive bladder, urinary retention, and fecal incontinence. Infection after sacral neurostimulation is costly and burdensome. Determining optimal perioperative management strategies to reduce the risk of infection is important to reduce this burden., Objective: We sought to identify risk factors associated with sacral neurostimulator infection requiring explantation, to estimate the incidence of infection requiring explantation, and identify associated microbial pathogens., Study Design: This is a multicenter retrospective case-control study of sacral neuromodulation procedures completed from Jan. 1, 2004, through Dec. 31, 2014. We identified all sacral neuromodulation implantable pulse generator implants as well as explants due to infection at 8 participating institutions. Cases were patients who required implantable pulse generator explantation for infection during the review period. Cases were included if age ≥18 years old, follow-up data were available ≥30 days after implantable pulse generator implant, and the implant was performed at the institution performing the explant. Two controls were matched to each case. These controls were the patients who had an implantable pulse generator implanted by the same surgeon immediately preceding and immediately following the identified case who met inclusion criteria. Controls were included if age ≥18 years old, no infection after implantable pulse generator implant, follow-up data were available ≥180 days after implant, and no explant for any reason <180 days from implant. Controls may have had an explant for reasons other than infection at >180 days after implant. Fisher exact test (for categorical variables) and Student t test (for continuous variables) were used to test the strength of the association between infection and patient and surgery characteristics. Significant variables were then considered in a multivariable logistic regression model to determine risk factors independently associated with infection., Results: Over a 10-year period at 8 academic institutions, 1930 sacral neuromodulator implants were performed by 17 surgeons. In all, 38 cases requiring device explant for infection and 72 corresponding controls were identified. The incidence of infection requiring explant was 1.97%. Hematoma formation (13% cases, 0% controls; P = .004) and pocket depth of ≥3 cm (21% cases, 0% controls; P = .031) were independently associated with an increased risk of infection requiring explant. On multivariable regression analysis controlling for significant variables, both hematoma formation (P = .006) and pocket depth ≥3 cm (P = .020, odds ratio 3.26; 95% confidence interval, 1.20-8.89) remained significantly associated with infection requiring explant. Of the 38 cases requiring explant, 32 had cultures collected and 24 had positive cultures. All 5 cases with a hematoma had a positive culture (100%). Of the 4 cases with a pocket depth ≥3 cm, 2 had positive cultures, 1 had negative cultures, and 1 had a missing culture result. The most common organism identified was methicillin-resistant Staphylococcus aureus (38%)., Conclusion: Infection after sacral neuromodulation requiring device explant is low. The most common infectious pathogen identified was methicillin-resistant S aureus. Demographic and health characteristics did not predict risk of explant due to infection, however, having a postoperative hematoma or a deep pocket ≥3 cm significantly increased the risk of explant due to infection. These findings highlight the importance of meticulous hemostasis as well as ensuring the pocket depth is <3 cm at the time of device implant., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the potential application of activated carbon (AC) and nonwoven fabric mats (NWFM) for thin-layer capping in remediation of sediments containing high amounts of carbon, nitrogen, and phosphorus. Laboratory column incubation experiments were performed to analyze the efficiencies of AC and NWFM for blocking nutrients. Under uncapped conditions, dissolved oxygen (DO) was exhausted within three days but under NWFM/AC capping conditions (with NWFM above the AC capping layer), the presence of DO was prolonged until Day 33. Chemical oxygen demand (COD) was lower under all capped conditions than under uncapped conditions, with lowest COD observed with NWFM/AC capping. NH 4 -N occupied the highest percentage of total nitrogen in the overlying water and its percentage increased as the DO concentration decreased. The capping efficiencies for NH 4 -N, T-N, and PO 4 -P with NWFM/AC capping were (66.0, 54.2, and 73.1) %, respectively, which were higher than for other capping conditions. In the case of T-P, capping efficiencies under all capping conditions were almost 100%, indicating that both AC and NWFM effectively interrupted phosphorus release from sediments. Placing NWFM above the AC capping layer was more effective than the opposite arrangement. It can be concluded that NWFM and AC can be successfully used for remediation of lake sediments with high amounts of nitrogen and phosphorus., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bare gold nanospheres have been shown to have anti-angiogenic effects but are optically unfavorable because their resonant wavelength lies in the visible spectrum. Here, we design gold nanodisks with a higher scattering capability than gold nanorods and with a resonant wavelength at near-infrared region - the area where the source of light utilized by optical coherence tomography (OCT) lies. With a physical synthesis system, we then fabricate 160-nm-sized gold nanodisks exhibiting resonant wavelength at 830 nm. The synthesized nanoparticles were successfully visualized in in vivo OCT at concentrations as low as 1 pM. After demonstrating their binding ability to vascular endothelial growth factor (VEGF), we show that they suppress VEGF-induced migration of endothelial cells. Finally, we demonstrate that intravitreally injected gold nanodisks attenuate neovascularization of oxygen-induced retinopathy in mice, in a dose dependent manner, such that they are cleared from the vitreous within 2 weeks without histologic or electrophysiologic toxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nanoparticles can be valuable therapeutic options to overcome physical barriers to reach central nervous system. Systemically administered nanoparticles can pass through blood-neural barriers; whereas, locally injected nanoparticles directly reach neuronal and perineuronal cells. In this review, we highlight the importance of size, surface charge, and shape of nanoparticles in determining therapeutic effects on brain and retinal diseases. These features affect overall processes of delivery of nanoparticles: in vivo stability in blood and other body fluids, clearance via mononuclear phagocyte system, attachment with target cells, and penetration into target cells. Furthermore, they are also determinants of nano-bio interfaces: they determine corona formation with proteins in body fluids. Taken together, we emphasize the importance of considerations on characteristics of nanoparticles more suitable for the treatment of brain and retinal diseases in the development of nanoparticle-based therapeutics., From the Clinical Editor: The central nervous system (CNS) remains an area where drug access and delivery are difficult clinically due to the blood brain barrier. With advances in nanotechnology, many researchers have designed and produced nanoparticle-based systems in an attempt to solve this problem. In this concise review, the authors described the current status of drug delivery to the CNS, based on particle size and shape. This article should stimulate more research to be done on future drug design., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Although lipid crystals (LCs) have received attention as a causative factor of plaque rupture, the mechanisms by which they increase plaque vulnerability are unknown. We examined whether solid-state LCs physically affect the adjacent extracellular matrix (ECM) using a combination of multimodal nonlinear optical (MNLO) imaging and finite element analysis (FEA)., Methods: The changes of ECMs affected by lipids in atherosclerotic arteries in apolipoprotein E-deficient mice (n = 32) fed a high-fat diet for 20-30 weeks were micro-anatomically visualized by a 3D MNLO imaging platform including CARS for lipids, TPEF for elastin, and SHG for collagen., Results and Conclusion: The TPEF signal of elastin was increased at the peripheral regions of LCs (<10 μm) compared with foam cell regions. In order to confirm the increase of elastin, biochemical assay (western blot) was performed. The protein level of elastin was increased approximately 2.25-fold (p = 0.024) in LC-rich arteries. Under the hypothesis that the increase of elastin resulted from the mechanical stimulus from solid-state LCs, MNLO images were subjected to FEA to simulate the displacement according to the expanding magnitude of the vessel during cardiac cycles. We found that microscale focal stress was increased specifically around the LCs. These FEA results corresponded with the increase of elastin observed by TPEF. These data suggest that LCs mechanically stimulate the adjacent ECM to alter the composition of ECM and cause vessel remodeling. The combination of MNLO imaging and FEA has great potential to verify the mechanical predictions in cardiovascular diseases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This study examined the stabilization and solidification (S/S) of mercury (Hg)-contaminated waste ash generated from an industrial waste incinerator using chemically bonded phosphate ceramic (CBPC) technology. A magnesium potassium phosphate (MKP; MgKPO4 · 6H2O) ceramic, fabricated from MgO and KH2PO4, and a calcium sodium phosphate (CNP; CaNaPO4) ceramic, fabricated from CaO and Na2HPO4, were used as solidification binders in the CBPC process, and Na2S or FeS was added to each solidification binder to stabilize the Hg-contaminated waste ash. The S/S processes were conducted under various operating conditions (based on the solidification binder and stabilization reagent, stabilization reagent dosage, and waste loading ratio), and the performance characteristics of the S/S sample under each operating condition were compared, including the Hg leaching value and compressive strength. The Hg leaching value of untreated Hg-contaminated waste ash was 231.3 μg/L, whereas the S/S samples treated using the MKP and CNP processes exhibited Hg leaching values below the universal treatment standard (UTS) limit (25 μg/L). Although the compressive strengths of the S/S samples decreased as the sulfide dosage and waste loading ratio were increased, most of the S/S samples fabricated by the MKP and CNP processes exhibited good mechanical properties., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Local application requires fewer nanoparticles than systemic delivery to achieve effective concentration. In this study, we investigated the potential toxicity and efficacy of bare titanium dioxide (TiO2) nanoparticles by local administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not affect the viability of retinal constituent cells within certain range of concentrations (~1.30μg/mL). Furthermore, local delivery of TiO2 nanoparticles did not induce any significant toxicity at the level of gene expression and histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low concentration (130ng/mL) without definite toxicity, these nanoparticles suppressed in vitro angiogenesis processes and in vivo retinal neovascularization in oxygen-induced retinopathy mice when they are administered intravitreally. Taken together, our results demonstrate that even TiO2 nanoparticles can be safely utilized for the treatment of retinal diseases at the adequate concentration levels, especially through local administration., From the Clinical Editor: In this paper the local application of titanium dioxide is described as a local treatment for retinal diseases associated with neovascularization. While these nanoparticles have known systemic toxicity, this work demonstrates that when applied locally in a mouse model, they can be used without observable toxicity even in their native forms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Human papillomavirus (HPV) vaccine uptake rate among young adult US women was only 23% in 2010. One way to improve this low rate is to administer the vaccine postpartum. We examined whether this population requires vaccination and whether they would be agreeable to receiving it free of charge after delivery., Study Design: Women 26 years of age or younger seeking prenatal care in publicly funded clinics in southeast Texas were interviewed in 2012 regarding their HPV vaccination status, barriers to vaccination, and whether they would be willing to receive this vaccine postpartum if offered free of charge. Medical charts were reviewed to extract additional information., Results: Overall, 13.0% (65 of 500) stated they had initiated and 7.6% (38 of 500) completed the 3-dose vaccine series. Ethnic differences were noted with 21.0% of non-Hispanic whites, 14.6% of blacks, and 9.3% of Hispanics (P = .002) initiating the vaccine and 13.5%, 7.8%, and 5.2% (P = .006) competing all 3 doses, respectively. Lowest initiation (4.2%) and completion (1.4%) rates were observed among recently immigrated Hispanic women. Those who had not graduated from high school and older women were less likely to have been vaccinated. Almost 83% of those who had not received any HPV doses or completed the series were willing to receive the injection free of charge in the hospital after their delivery., Conclusion: HPV vaccine uptake rates are very low among women receiving prenatal care in southeast Texas. Offering this vaccine free of charge to postpartum women could be an effective strategy in this population because 5 of 6 women favored receiving it in this setting., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To evaluate the effects and safety of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in the early stage after an acute ischemic event and the improvement of present symptoms in patients with intracranial atherosclerotic occlusive disease with stroke/stroke in progress., Methods: From 2006 to 2010, 20 patients (15 males and five females) with atherosclerotic cerebrovascular disease were treated with an STA-MCA bypass. All of the patients presented with an acute ischemic stroke or stroke in progress despite maximal medical treatment. The patients underwent an STA-MCA bypass within 7 days from symptom onset. The clinical outcome and hemodynamic study of the 20 patients were preoperatively and postoperatively investigated. A pooled analysis was performed, and the results were compared with those obtained from other delayed STA-MCA bypass studies., Results: Among the 20 patients who underwent an early STA-MCA bypass, fourteen (70%) patients achieved a good functional outcome (mRS 0, n=3; mRS 1, n=9; mRS 2, n=2). Prior to surgery, the mean basal regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) in the symptomatic hemisphere were 37.3±4.3 ml/100 g/min and -1.68±2.9%. The mean basal rCBF and CVR had significantly increased postoperatively, and no reperfusion-induced hemorrhage had occurred. In the pooled analysis, no significant differences were observed in the clinical outcome (P=0.328) or in the incidence of postoperative complications (P=0.516) between patients who underwent an early STA-MCA bypass and in patients who underwent a delayed STA-MCA bypass in previous studies., Conclusions: In this study, which consisted of 20 carefully selected patients with acute ischemic stroke, an early STA-MCA bypass was safely and effectively performed, and in some cases, an early STA-MCA bypass resulted in rapid neurological improvement. An early STA-MCA bypass was beneficial in select patients who had acute ischemic stroke with imaging evidence of a small infarction., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Changes in cholesterol ester (CE) content regulate the progression of atherosclerosis. However, the spatial dynamics of CE subsets and their quantitative changes during lesion progression are not well understood due to a lack of appropriate imaging techniques. In this study, we developed an imaging-based analysis method to map the distribution of CE subsets using time-of-flight secondary ion mass spectrometry (ToF-SIMS)., Methods: Serial sections of atherosclerotic aortic sinuses from apolipoprotein E knock-out mice (n = 15) fed a 0.15% high-fat diet for 12-20 weeks were examined by ToF-SIMS., Results and Conclusion: We found that the ratio of cholesteryl palmitate (Ch-PA) to cholesteryl oleate (Ch-OA) increased by approximately 99% (p = 0.02) as atherosclerosis progressed, whereas the ratios of cholesteryl linoleate (p = 0.09) and cholesteryl stearate (p = 0.22) to Ch-OA did not change significantly. In advanced atherosclerotic plaques, in situ and in-vitro cell death assays showed that local Ch-PA densities were highly correlated with an increase in the number of apoptotic cells. These results suggest that increased Ch-PA may contribute to the formation of a necrotic core by increasing cell death. Our results indicate that the regional ratio of CEs as measured by ToF-SIMS might be a valuable new marker of atherosclerotic progression., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Although mercury (Hg) is a poisonous substance that has harmful effects on the environment and in humans, it is widely used in industrial facilities and in goods for daily use. Given the recent recognition of the risk posed by Hg exposure, the international society is trying to reduce the use of and demand for Hg by implementing more stringent regulations. Relevant policies and laws recommend alternatives to Hg or prohibit the use of Hg in certain applications. In addition, it is recommended that the amount of Hg used in Hg-containing products be reduced or that manufacturers discontinue such products. Disposal methods for elemental Hg include landfill, incineration, stabilization/solidification, and permanent storage. In this review, the major sources of Hg and expected amount of surplus Hg are described after summarizing international policies and plans for Hg management. In addition, a study on the establishment of proper storage facilities was performed by comparing existing Hg storage technologies with newly designed technologies for facilities where surplus Hg may be stored permanently., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Type I collagen is a major extracellular matrix component and its hierarchical structure plays an essential role in the regulation of cellular behavior. Here, we have analyzed the changes in the morphological, chemical, and mechanical properties of collagen fibrils induced by acidic and thermal treatments and the influence on the cellular response of MC3T3-E1 cells. Morphological changes induced by the disintegration of the fibrillar structure of collagen were observed using atomic force microscopy. The changes in the surface chemistry due to the disassembly of native collagen fibrils were observed using time-of-flight secondary ion mass spectroscopy (ToF-SIMS). ToF-SIMS spectra were very sensitive to changes in the molecular configuration of the collagen fibrils induced by acidic and thermal treatments due to the extreme surface specificity. In addition, ToF-SIMS showed clear and reproducible changes in the surface amino acid composition corresponding to the acidic and thermal treatments of collagen fibrils. Based on the quantitative map of surface elastic modulus measured by contact-resonance force microscopy, acid and thermally treated collagen showed a lower elastic modulus than native collagen fibrils. Compared with native collagen fibrils, reduced cell spreading and decreased viability of MC3T3-E1 cells were observed on both the acid and thermally treated collagen., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Angiogenesis-related blindness indicates the spectrum of retinal diseases that are caused by pathological angiogenesis, resulting in catastrophic vision loss. We aimed to demonstrate the antiangiogenic effect of silicate nanoparticles (SiNPs) on the retinal neovascularization. No direct toxicity of SiNPs was observed on retinal neuronal or endothelial cells, nor on the retinal tissue. Furthermore, intravitreal injection of SiNPs effectively reduced anomalous retinal angiogenesis in oxygen-induced retinopathy mice. SiNPs also effectively inhibited in vitro vascular endothelial growth factor (VEGF)-induced angiogenesis. Via suppression of VEGF receptor-2 phosphorylation induced by VEGF, SiNPs blocked ERK 1/2 activation. SiNPs could be an inhibitor of the potency and safety of retinal neovascularization that is mediated by VEGF and utilized in the treatment of angiogenesis-related blindness., From the Clinical Editor: In this important preclinical study, silicate NP-s are studied to address retinal neovascularization, an important pathomechanism of different retinal diseases that could lead to catastrophic vision loss. The authors conclude that SiNP-s could be utilized as inhibitors of retinal neovascularization mediated by VEGF and propose future applications in the treatment of angiogenesis-related blindness., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Metabolic tissues, including skeletal muscle, adipose tissue and the digestive system, dynamically secrete various factors depending on the metabolic state, communicate with each other and orchestrate functions to maintain body homeostasis. Skeletal muscle secretes cytokines such as interleukin-6 (IL-6), IL-15, fibroblast growth factor-21 (FGF21) and IL-8. These compounds, myokines, play important roles in biological homeostasis such as energy metabolism, angiogenesis and myogenesis. New technological advances have allowed secretomics - analysis of the secretome - to be performed. The application of highly sensitive mass spectrometry makes qualitative and quantitative analysis of the secretome of skeletal muscle possible. Secretory proteins derived from skeletal muscle cells under various conditions were analyzed, and many important factors were suggested. In-depth studies of the secretome from metabolic cells in various conditions are strongly recommended. This study will provide information on methods of novel communication between metabolic tissues., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We have previously reported anti-obesity effects of Lysimachia foenum-graecum in high-fat diet (HFD)-induced obesity model. Here we isolated a triterpene saponin foenumoside B as an active component of L. foenum-graecum. Foenumoside B blocked the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner with an IC50 of 0.2 μg/ml in adipogenesis assay and suppressed the induction of PPARγ, the master regulator of adipogenesis. Foenumoside B induced the activation of AMP-activated protein kinase (AMPK), and modulated the expression of genes involved in lipid metabolism towards lipid breakdown in differentiated adipocytes. In mouse model, oral administration of foenumoside B (10mg/kg/day for 6 weeks) reduced HFD-induced body weight gain significantly without affecting food intake. Treatment of foenumoside B suppressed lipid accumulation in white adipose tissues and the liver, and lowered blood levels of glucose, triglycerides, ALT, and AST in HFD-induced obese mice. Consistent with the in vitro results, foenumoside B activated AMPK signaling, suppressed the expression of lipogenic genes, and enhanced the expression of lipolytic genes in vivo. Foenumoside B also blocked HFD-induced proinflammatory cytokine production in adipose tissue, suggesting its protective role against insulin resistance. Taken together, these findings demonstrate that foenumoside B represents the anti-obesity effects of L. foenum-graecum, and suggest therapeutic potential of foenumoside B in obesity and obesity-related metabolic diseases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes, as they play crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here, we report the crystal structures of the biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK). The phosphorylated Ser222 binds to the putative dimer interface of BC, disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product. This structure shows that the compound binds to the binding site of phosphorylated Ser222, implying that its inhibition mechanism is the same as that of phosphorylation by AMPK., (Copyright 2009 Elsevier Inc. All rights reserved.)

Superoxide is the most important armory on the primary defense line of monocytes against invading pathogens, and the identification of new stimuli and the characterization of the regulatory mechanism of superoxide generation are of paramount importance. In this study, we identified 3 novel peptides by screening a synthetic hexapeptide combinatorial library and modification of 1 of the peptides. The isolated peptides that can induce superoxide generation in human monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH(2) (HFYLPM), Met-Phe-Tyr-Leu-Pro-Met-CONH(2) (MFYLPM), and His-Phe-Tyr-Leu-Pro-D-Met-CONH(2) (HFYLPm). All 3 peptides also caused intracellular calcium ([Ca(++)](i)) rise. We tested the specificities of the peptides on cells of different origin by looking at [Ca(++)](i) rise. All 3 peptides acted specifically on leukocytes and not on nonimmune cells. Among leukocytes, HL60 and Jurkat T cells were stimulated specifically by MFYLPM or HFYLPM, respectively. As a physiologic characteristic of the peptides, we observed that all 3 peptides induced chemotactic migration of monocytes. Studying receptor specificity, we concluded that the 3 peptides might act on some shared and some distinct receptor(s) on leukocytes. Studying intracellular signaling set in motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm, induced chemotaxis via phosphatidylinositol-3 kinase and protein kinase C. Because HFYLPM, MFYLPM, and HFYLPm not only exhibit different specificities depending on cell type and status of differentiation but also stimulate cells via distinct receptors and signaling, the 3 novel peptides might be useful tools to study leukocyte activation.

The peptides inhibiting HIV-1 protease were isolated from the hydrolysate of oyster (Crassostrea gigas) proteins prepared with thermolysin. The amino acid sequences of the peptides were determined as Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu-Glu-Tyr-Ser-Leu. These sequences exist in some proteins of variola major virus or human cytomegalovirus. Chemically synthesized Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu-Glu-Tyr-Ser-Leu showed IC50 values of 20 and 15 nM, respectively, and behaved as competitive inhibitors for HIV-1 protease with Ki values of 13 and 10 nM, respectively. These peptides were more potent as an HIV-1 protease inhibitor than pepstatin A.

Although the 210 and 190-kDa proteins are the most frequently detected antigens reacting with sera of patients with paraneoplastic pemphigus (PNP) in immunoblot analysis, there is still uncertainty as to the nature of these PNP antigens. To isolate and characterize a cDNA clone encoding the 210-kDa PNP antigen, we screened a human keratinocyte lambda gt 11 cDNA expression library by the immunoperoxidase method with serum IgG from a PNP patient. The IgG used for the immunoscreening of a keratinocyte cDNA expression library recognized 210- and 190-kDa antigens by immunoblotting. A single clone, called here the PNP clone, producing a fusion protein that reacted strongly with the patient's IgG, was further characterized. Only the PNP patient's IgG, but not IgG from a normal control, pemphigus foliaceus, or pemphigus vulgaris patients, bound the plaques of this positive clone. Furthermore, PNP IgG affinity purified on plaques of this clone, but not unrelated clones, bound to keratinocyte cell surfaces by immunofluorescence and reacted with the 210-kDa PNP antigen by immunoblotting. EcoRI digestion of the clone's cDNA insert demonstrated a 1.4-kbp fragment. This cDNA insert was placed into a M13 mp 18 vector and sequenced. Sequence analysis revealed that the cDNA insert of the PNP clone encodes a part of the central rod domain and the COOH-terminal C domain of envoplakin, a newly defined precursor of the cornified envelope that is homologous to desmoplakin. This result demonstrates that the 210-kDa PNP antigen is envoplakin and PNP is an autoimmune disease that produces autoantibodies against intermediate filament-associated proteins in desmosomes and hemidesmosomes, desmoplakin, bullous pemphigoid antigen 1 (BPAG 1), and envoplakin.

Leghorn spent hen mechanically deboned chicken meat (MDCM) was utilized in the preparation of a value-added chicken sausage. The sausage was manufactured by combining MDCM with hand-deboned skinless chicken thigh meat, fat replacer ingredients (blend of modified food starch and oat flour), and either 1) no ingredient with antioxidant properties, 2) Colorlife powdered rosemary concentrate, 3) Herbalox Type O oleoresin rosemary extract or 4) Tenox 6 antioxidant. The 454-g sausage chubs were stored at 4 +/- 1 C (refrigerated) and -20 +/- 1 C (frozen) for 10 d and 6 mo, respectively. A shelf life evaluation (based on daily examination of product, panelists responses, and psychrotrophic organism counts) of 8 d and 6 mo was attained for the sausage stored at 4 +/- 1 and -20 +/- 1 C, respectively. Flavor intensity, texture, and color were maintained for all treatments, and no significant (P > 0.05) off-flavors were detected through 8 d and 6 mo storage. Colorlife and Herbalox rosemary ingredients, and Tenox 6 antioxidant had no adverse effects on sensory characteristics of the chicken sausage. Psychrotrophic organisms increased with increased storage time for the refrigerated sausage, and remained static for the frozen sausage.