While many in vivo and in vitro toxicology studies of multi-walled carbon nanotubes (MWCNTs) have already indicated that exposure to MWCNTs can potentially induce health effects in humans, the actual health effects of MWCNTs among exposed workers are not yet known. Moreover, the levels of exposure and internal doses of MWCNTs are becoming more and more important for estimating the health effects resulting from exposure to MWCNTs. However, information on biomonitoring and exposure to MWCNTs remains limited. Therefore, the authors conducted a health surveillance study in a workplace that manufactures MWCNTs, including assessment of the personal and area exposure levels to MWCNTs, a walk-through evaluation of the manufacturing process, and collection of blood and exhaled breath condensates (EBCs) from the MWCNT manufacturing and office workers. In addition, a pulmonary function test was also conducted on the MWCNT manufacturing workers (9) and office workers (4). The worker exposure to elemental carbon was found to be 6.2-9.3 μg/m(3) in the personal samplings and 5.5-7.3 μg/m(3) in the area samplings. Notwithstanding, the workers exhibited a normal range of hematology and blood biochemistry values and normal lung function parameters. When analyzing the EBCs, the malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE) and n-hexanal levels in the MWCNT manufacturing workers were significantly higher than those in the office workers. The MDA and n-hexanal levels were also significantly correlated with the blood molybdenum concentration, suggesting MDA, n-hexanal and molybdenum as useful biomarkers of MWCNT exposure.

Stretchable artificial synaptic devices are promising for integration into soft neuromorphic systems. However, the organic electrochemical transistor (OECT)‐based synaptic device is challenging due to the difficulty of obtaining high mechanical deformability and durability as well as high long‐term plasticity (LTP) and retention time. Herein, a highly stable and stretchable synaptic OECT fabricated on a 3D mogul‐patterned substrate with stress absorption capability with improved synaptic properties is reported. The mechanical stability of a poly(3,4‐ethylenedioxythiophene)polystyrene sulfonate (PEDOT:PSS) channel and, in turn, the OECT is improved by adding additives in the channel. Synaptic properties including synaptic weight (SW), LTP, and retention time could be tuned and improved by adopting a Nafion membrane between the channel and the gate electrode, which modifies the transport dynamics of ions in the electrolyte across the membrane. This approach paves a way for improving and tuning the synaptic properties of stretchable biomimetic OECT synapses.

Vascular dysfunction is correlated to the incidence and severity of Alzheimer’s disease. In a mouse model of Alzheimer’s disease (APP/PS1) using in vivo, time-lapse, multiphoton microscopy, we found that occlusions of the microvasculature alter amyloid-beta (Aβ) plaques. We used several models of vascular injury that varied in severity. Femtosecond laser-induced occlusions in single capillaries generated a transient increase in small, cell-sized, Aβ deposits visualized with methoxy-X04, a label of fibrillar Aβ. After occlusions of penetrating arterioles, some plaques changed morphology, while others disappeared, and some new plaques appeared within a week after the lesion. Antibody labeling of Aβ revealed a transient increase in non-fibrillar Aβ one day after the occlusion that coincided with the disappearance of methoxy-X04-labeled plaques. Four days after the lesion, anti-Aβ labeling decreased and only remained in patches unlabeled by methoxy-X04 near microglia. Histology in two additional models, sparse embolic occlusions from intracarotid injections of beads and infarction from photothrombosis, demonstrated increased labeling intensity in plaques after injury. These results suggest that microvascular lesions can alter the deposition and clearance of Aβ and confirm that Aβ plaques are dynamic structures, complicating the interpretation of plaque burden as a marker of Alzheimer’s disease progression.

Abstract:This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [ 14 C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5-and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake OPEN ACCESSMolecules 2015, 20 17394 inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5-and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition.

BackgroundRapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices.Methods and findingsWe performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA—with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA.ConclusionsOriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active enzymes on NPs as the basis for a highly rapid and sensitive biomarker detection platform. This addresses a key challenge in developing a PoCT platform for time sensitive and difficult to diagnose pathologies.