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Temporal lobe epilepsy is the most common focal epilepsy syndrome and has a broad spectrum of presentations. Nevertheless, isolated vestibular symptoms without other symptoms typical of temporal lobe seizures are relatively rare. Here, we report one female patient who suffered from chronic refractory vertigo and had inappropriate pharmacotherapy for several years. Eventually, epileptic vertigo and dizziness (ictal vertigo) were accurately diagnosed by detailed history taking and serial examinations assisted by sphenoid electroencephalography. Awareness of this unique syndrome is important in the diagnosis of patients with epileptic vertigo and dizziness.

Background/purpose: FAST and Stroke-112 are two campaigns to reduce the emergency room arrival time of stroke patients. No study has compared the effectiveness of these campaigns. This study aimed to compare recalling capacity of people in these two campaigns., Methods: A prospective, open-label randomized study was conducted in 2019. Recall ability for the items of the two campaigns on the 5th and 30th days post-education was compared using non-parametric methods. Subject characteristics including age, education level, presence of stroke in co-residents, and habitual language were evaluated using multiple ordered logistic regression., Results: There were 202 participants in FAST group and 193 participants in Stroke-112 group who completed the study. No differences were observed between the two groups in recall ability, either on day 5 or day 30 after receiving education. For both campaigns, recall ability was better for signs in the face (FAST: 87.1%, Stroke-112: 86.5%) and the arm (FAST: 87.1%, Stroke-112: 88.1%) than for abnormality in speech (FAST: 78.7%, Stroke-112: 76.7%) on day 5. Recall ability on day 30 remained the same only for the arm item (FAST: 86.1%, Stroke-112: 88.6%). The recall ability was correlated to education level equal or more than 7 years in FAST group, and was inversely correlated to age and being a stroke patient in Stroke-112 group., Conclusion: We found no difference in recall ability between the 2 campaigns. Education level was associated with recallability of FAST, and age and stroke history were associated with recallability of Stroke-112., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease., Objectives: To establish the normal echocardiographic parameters for Maltese dogs., Methods: In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis., Results: The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight., Conclusion: This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Veterinary Science.)

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H 2 O 2 -induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.

This paper proposes a novel μ-hydroxo-bridged dinuclear macrocyclic zinc complex, {[Zn(C 10 H 20 N 8 )] 2 (OH)}(BF 4 ) 3 . The structure was determined by X-ray crystallography: Monoclinic, C2/c, a = 25.4632(6), b = 10.9818(3), c = 15.7522(4) Å, Z = 8, R 1 = 0.0233, wR 2 = 0.0557, based on reflections I > 2σ(I). The complex was successfully reacted with graphene oxide to form a μ-hydroxo-bridged dinuclear macrocyclic Zn complex/reduced graphene oxide composite. To evenly disperse the Zn- and N-rich complex onto the surface of the reduced graphene oxide, and to enhance the electrocatalytic property of the graphene composites, a soluble molecular grafting method was used here. The graphene-based composites were applied as the counter electrodes (CEs) of dye-sensitized solar cells. Current density-voltage measurements revealed that the conversion efficiency of the GO/Zn (1 : 10) sample was 7.78%, which was better than that of Pt CE (7.49%). GO/Zn (1 : 10) CE exhibited the lowest impedance (R CE = 9.90 Ω), which was better than that of Pt CE (R CE = 66.1 Ω), showing that GO/Zn CEs can reduce the impedance at the CE/electrolyte interface. The proposed method is simple, and the composite materials can potentially replace conventional Pt, optimizing efficiency and reducing production cost.

Nickel-doped FeS 2 /rGO composites were synthesized as multifunctional materials via a facile hydrothermal method. The synthesized materials were characterized with XRD, FESEM, XPS, and TEM-SAED for structural, morphological and chemical studies. To study their electrochemical properties, all the synthesized composites were subjected to cyclic voltammetry tests. The optimum composite revealed high catalytic activity with high peak current density, limiting current, and efficiency of 7.60% for DSSC, which surpassed that of a platinum-based counter electrode (6.69%). The efficiency of the DSSC was significantly supported by interfacial studies and electron lifetime studies, and it exhibited lower charge transfer resistance and higher electron lifetime, respectively. Moreover, the fabricated DSSCs with high efficiency were subjected to transient photo-response studies and showed a stable current response with multiple photo-ON and OFF cycles for a period of 600 s. To broaden the application of the synthesized material, it was used as an electrochemical sensor for the efficient sensing of hydrogen peroxide (H 2 O 2 ). The sensing electrode was modified with the optimum Ni-doped FeS 2 /rGO composite, and voltammetric detection was carried out in the hydrogen peroxide concentration range of 4-100 μM. Thus, the synthesized material can be applied in DSSCs and as an electrochemical H 2 O 2 sensor.

Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. The in vitro experiments showed that cavitation activity was enhanced more significantly during dual-frequency sonication than single-frequency sonication in higher concentration of MBs. The pigskin penetration depth in the group in which dual-frequency US was combined with MBs was 1.54 and 2.86 times greater than for single-frequency US combined with MBs and in the control group, respectively; the corresponding increases in the release rate of Mx at 18 hours in in vitro Franz-diffusion-cell experiments were 24.9% and 43.7%. During 21 days of treatment in C57BL/6J mice experiments, the growth rate at day 11 in the group in which dual-frequency US was combined with MBs increased by 2.07 times compared to single-frequency US combined with MBs. These results indicate that dual-frequency US-mediated MB cavitation can significantly increase both skin permeability and transdermal drug delivery. At the same US power density, hair growth was greater in the group with dual-frequency US plus MBs than in the group with single-frequency US plus MBs, without damaging the skin in mice.

Background: Epilepsy is a neurological disorder characterized by abnormal neuron discharge, and one-third of epilepsy patients suffer from drug-resistant epilepsy (DRE). The current management for DRE includes epileptogenic lesion resection, disconnection, and neuromodulation. Neuromodulation is achieved through invasive electrical stimulus including deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation (RNS). As an alternative therapy, transcranial focused ultrasound (FUS) can transcranially and non-invasively modulate neuron activity., Objective: This study seeks to verify the use of FUS pulsations to suppress spikes in an acute epileptic small-animal model, and to investigate possible biological mechanisms by which FUS pulsations interfere with epileptic neuronal activity., Methods: The study used a total of 76 Sprague-Dawley rats. For the epilepsy model, rats were administered pentylenetetrazol (PTZ) to induce acute epileptic-like abnormal neuron discharges, followed by FUS exposure. Various ultrasound parameters were set to test the epilepsy-suppressing effect, while concurrently monitoring and analyzing electroencephalogram (EEG) signals. Animal behavior was monitored and histological examinations were conducted to evaluate the hazard posed by ultrasound exposure and the expression of neuronal activity markers. Western blotting was used to evaluate the correlation between FUS-induced epileptic suppression and the PI3K-mTOR signaling pathway., Results: We observed that FUS pulsations effectively suppressed epileptic activity and observed EEG spectrum oscillations; the spike-suppressing effect depended on the selection of ultrasound parameters and highly correlated with FUS exposure level. Expression level changes of c-Fos and GAD65 were confirmed in the cortex and hippocampus, indicating that FUS pulsations deactivated excitatory cells and activated GABAergic terminals. No tissue damage, inflammatory response, or behavioral abnormalities were observed in rats treated with FUS under these exposure parameters. We also found that the FUS pulsations down-regulated the S6 phosphorylation and decreased pAKT expression., Conclusion: Our results suggest that pulsed FUS exposure effectively suppresses epileptic spikes in an acute epilepsy animal model, and finds that ultrasound pulsation interferes with neuronal activity and affects the PTZ-induced PI3K-Akt-mTOR pathway, which might help explain the mechanism underlying ultrasound-related epileptic spike control., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene encoding the huntingtin (Htt) protein, which results in a protein containing an abnormally expanded polyglutamine (polyQ) sequence. The expanded polyQ in the Htt protein is toxic to brain cells. No therapy exists to delay disease progression., Methods: This study describes a gene-liposome system that synergistically applied focused ultrasound (FUS)-blood-brain barrier (BBB) opening for rescuing motor and neuropathological impairments when administered from pre to post-symptomatic transgenic mouse models of HD. DPPC liposomes (LPs) are designed to carry glia cell line-derived neurotrophic factor (GDNF) plasmid DNA (GDNFp) to form a GDNFp-liposome (GDNFp-LPs) complex. Pulsed FUS exposure with microbubbles (MBs) was used to induce BBB opening for non-viral, non-invasive, and targeted gene delivery into the central nervous system (CNS) for therapeutic purposes., Results: FUS-gene therapy significantly improved motor performance with GDNFp-LPs + FUS treated HD mice equilibrating longer periods in the animal behavior. Reflecting the improvements observed in motor function, GDNF overexpression results in significantly decreased formation of polyglutamine-expanded aggregates, reduced oxidative stress and apoptosis, promoted neurite outgrowth, and improved neuronal survival. Immunoblotting and histological staining further confirmed the neuroprotective effect from delivery of GDNF genes to neuronal cells., Conclusions: This study suggests that the GDNFp-LPs plus FUS sonication can provide an effective gene therapy to achieve local extravasation and triggered gene delivery for non-invasive in vivo treatment of CNS diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Focused ultrasound (FUS) with the presence of microbubbles induces blood brain barrier (BBB) opening in targeted areas and facilitates drug delivery. However, recent studies have indicated that FUS-BBB opening with excessive exposure levels may be associated with inflammatory response and cellular/tissue damage. Multiple weekly FUS exposures have been shown to be safe for human subjects. However the effect of more frequent FUS exposures is still unknown. This study examines whether frequent focused ultrasound blood brain barrier opening is associated with aggravated behavioral, histopathologic change or brain tissue damage. Two protocols of focused ultrasound blood brain barrier opening were devised using different microbubble doses (0.15 µl/kg and 0.4 µl/kg). Focused ultrasound exposure at a threshold level of BBB-opening, below-threshold level, or above level for intracerebral hemorrhage were delivered every 2 days. Animal behavioral and physiological changes were examined and recorded. Brain tissue was examined for hemorrhage and apoptosis. Results indicate that frequent exposure of excessive focused ultrasound (1.4 mechanical index) produced minor and short-term behavioral changes despite significant tissue damage, while frequent BBB opening with threshold or below-threshold FUS exposure (0.33-0.8 mechanical index) did not cause behavioral or histological change. Immunofluorescent examination of rat brain tissue indicated that excessive doses of microbubble administration induce an apparent cellular apoptotic response, which may be exacerbated by intracerebral hemorrhage. Experimental results suggest that frequent focused ultrasound blood brain barrier opening with sufficient ultrasound exposure level and a microbubble dose can be safe and pose minimal risk to brain tissue.

Focused ultrasound phased array systems have attracted increased attention for brain therapy applications. However, such systems currently lack a direct and real-time method to intraoperatively monitor ultrasound pressure distribution for securing treatment. This study proposes a dual-mode ultrasound phased array system design to support transmit/receive operations for concurrent ultrasound exposure and backscattered focal beam reconstruction through a spherically focused ultrasound array. A 256-channel ultrasound transmission system was used to transmit focused ultrasonic energy (full 256 channels), with an extended implementation of multiple-channel receiving function (up to 64 channels) using the same 256-channel ultrasound array. A coherent backscatter-received beam formation algorithm was implemented to map the point spread function (PSF) and focal beam distribution under a free-field/transcranial environment setup, with the backscattering generated from a strong scatterer (a point reflector or a microbubble-perfused tube) or a weakly scattered tissue-mimicking graphite phantom. Our results showed that PSF and focal beam can be successfully reconstructed and visualized in free-field conditions and can also be transcranially reconstructed following skull-induced aberration correction. In vivo experiments were conducted to demonstrate its capability to preoperatively and semiquantitatively map a focal beam to guide blood-brain barrier opening. The proposed system may have potential for real-time guidance of ultrasound brain intervention, and may facilitate the design of a dual-mode ultrasound phased array for brain therapeutic applications.

Context: Arsenic poisoning commonly occurs through exposure to water contaminated with arsenic and causes long-term symptoms. Of all the arsenic derivatives, arsenite is the one of the most toxic compounds. However, the toxicity of arsenite during developmental stages is still unclear., Objective: In this study, we performed a metabolomic analysis of arsenite responses in embryonic zebrafish., Materials and Methods: Embryonic zebrafish were used as an animal model in this study. They were exposed to sodium arsenite under different concentrations (0.5, 1.0, 2.0, and 5.0 mg/L) in 24 h, 48 h and 72 h post fertilization. Changes in morphology were observed through a light microscope. Changes in metabolomics were identified using an ultraperformance liquid chromatography quadrupole time-of-flight system., Results: The IC 50 range was 0.75 ± 0.25 mg/L. Compared with the control group, the embryonic lethality rate decreased to 33.3% under 1.0 mg/L of arsenite treatment, whereas it decreased to 20.0% under 2.0 mg/L of arsenite treatment. Numerous body axis curvatures were also observed under treatment with 2.0 and 5.0 mg/L of arsenic. Pericardium and yolk sac edema were randomly discovered and found to worsen over time. Moreover, the 10 metabolites with the highest variable importance in projection score were identified as potential biomarkers for arsenic exposure., Conclusion: Arsenic exposure not only leads to a change in the morphology of embryonic zebrafish but also disturbs the metabolism of zebrafish in early developmental stages., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Focused ultrasound (FUS) exposure with microbubbles can transiently open the blood-brain barrier (BBB) to deliver therapeutic molecules into CNS tissues. However, delivered molecular distribution/concentration at the target need to be controlled. Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI) is a well-established protocol for monitoring the pharmacokinetic/pharmacodynamic behavior of FUS-BBB opening. This study investigates the feasibility of using DCE-MRI to estimate molecular CNS penetration under various exposure conditions and molecule sizes. In the 1 st stage, a relationship among the imaging index K trans , exposure level and molecular size was calibrated and established. In the 2 nd stage, various exposure levels and distinct molecules were applied to evaluate the estimated molecular concentration discrepancy with the quantified ones. High correlation (r 2  = 0.9684) between K trans and transcranial mechanical index (MI) implies K trans can serve as an in vivo imaging index to mirror FUS-BBB opening scale. When testing various molecules with the size ranging 1-149 kDa, an overall correlation of r 2  = 0.9915 between quantified and predicted concentrations was reached, suggesting the established model can provide reasonably accurate estimation. Our work demonstrates the feasibility of estimating molecular penetration through FUS-BBB opening via DCE-MRI and may facilitate development of FUS-induced BBB opening in brain drug delivery.

A novel series of reduced graphene oxide (RGO)/macrocyclic iron (Fe) complex hybrid materials were synthesized and then used in the production of counter electrodes (CEs) for dye-sensitized solar cells (DSSCs). The electrode properties of various CEs were comprehensively analyzed using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, energy dispersive spectroscopy, Raman spectroscopy, X-ray diffraction, and cyclic voltammetry analyses. DSSCs, based on various CEs, were characterized using current density-voltage, incident monochromatic photon-to-current conversion efficiency, and electrochemical impedance spectroscopy measurements. DSSCs fabricated using the RGO/macrocyclic Fe nanocomposite CEs yielded an efficiency of 6.75%. The RGO/Fe CEs exhibited efficient electrocatalytic capability because catalytic Fe particles were uniformly distributed on the surface of RGO. The results indicated that a DSSC with a RGO/Fe CE can exhibit an efficiency comparable to that of a platinum (Pt) CE DSSC and can therefore replace conventional Pt CE DSSCs to lower the cost of solar cells., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50-63% in groups E and F, to 67-83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.

Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as surrogates to allow molecule-penetrated quantification, BBB-opened observation, and MBs circulation/persistence. Cavitation activity was measured via the passive cavitation detection (PCD) setup to correlate with the exposure level and the histological effect. Under given and identical MB concentrations, the three MBs induced similar and equivalent BBB-opening effects and persistence. In addition, a treatment paradigm by adapting exposure time is proposed to compensate MB decay to retain the persistence of BBB-opening efficiency in multiple FUS exposures. The results potentially improve understanding of the equivalence among MBs in focused ultrasound CNS drug delivery, and provide an effective strategy for securing persistence in this treatment modality.

The surface morphology in polycrystalline silicon (poly-Si) film is an issue regardless of whether conventional excimer laser annealing (ELA) or the newer metal-induced lateral crystallization (MILC) process is used. This paper investigates the stress distribution while undergoing long-term mechanical stress and the influence of stress on electrical characteristics. Our simulated results show that the nonuniform stress in the gate insulator is more pronounced near the polysilicon/gate insulator edge and at the two sides of the polysilicon protrusion. This stress results in defects in the gate insulator and leads to a nonuniform degradation phenomenon, which affects both the performance and the reliability in thin-film transistors (TFTs). The degree of degradation is similar regardless of bending axis (channel-length axis, channel-width axis) or bending type (compression, tension), which means that the degradation is dominated by the protrusion effects. Furthermore, by utilizing long-term electrical bias stresses after undergoing long-tern bending stress, it is apparent that the carrier injection is severe in the subchannel region, which confirms that the influence of protrusions is crucial. To eliminate the influence of surface morphology in poly-Si, three kinds of laser energy density were used during crystallization to control the protrusion height. The device with the lowest protrusions demonstrates the smallest degradation after undergoing long-term bending.

Two new organic dyes-BPDTA and BTTA-possessing dual D-π-A units have been synthesized, characterized, and employed as efficient sensitizers for dye-sensitized solar cells. The two individual D-π-A, which are based on (E)-3-(5'-(4-(bis(4-(hexyloxy)phenyl)amino)phenyl)-[2,2'-bithiophen]-5-yl)-2-cyanoacrylic acid unit (D21L6), are connected directly between phenylene or thiophene within linear π-conjugated backbone to constitute a highly twisted architecture for suppressing the dye aggregation. The new dianchoring dyes exhibited pronounced absorption profile with higher molar extinction coefficient, which is consistent with the results obtained from density functional theory (DFT) calculations. The theoretical analysis also indicated that the charge transfer transition is mainly constituted of HOMO/HOMO-1 to LUMO/LUMO+1 that were found to be located on donor and acceptor segments, respectively. Theoretical calculations give the distance between two binding sites of 19.50 Å for BPDTA and 12.04 Å for BTTA. The proximity between two anchoring units of BTTA results in superior dye loading and, hence, higher cell efficiency. The BTTA-based device yielded an optimized efficiency of 6.86%, compared to 6.61% for the BPDTA-based device, whereas the model sensitizer D21L6 only delivered an inferior performance of 5.33% under similar conditions. Our molecular design strategy thus opens up a new horizon to establish efficient dianchoring dyes.

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Focused ultrasound (FUS)-induced with microbubbles (MBs) is a promising technique for noninvasive opening of the blood-brain barrier (BBB) to allow targeted delivery of therapeutic substances into the brain and thus the noninvasive delivery of gene vectors for CNS treatment. We have previously demonstrated that a separated gene-carrying liposome and MBs administration plus FUS exposure can deliver genes into the brain, with the successful expression of the reporter gene and glial cell line-derived neurotrophic factor (GDNF) gene. In this study, we further modify the delivery system by conjugating gene-carrying liposomes with MBs to improve the GDNF gene-delivery efficiency, and to verify the possibility of using this system to perform treatment in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal disease model. FUS-BBB opening was verified by contrast-enhanced MRI, and GFP gene expression was verified via in vivo imaging system (IVIS). Western blots as well as enzyme-linked immunosorbent assay (ELISA) were conducted to measure protein expression, and immunohistochemistry (IHC) was conducted to test the Tyrosine hydroxylase (TH)-neuron distribution. Dopamine (DA) and its metabolites as well as dopamine active transporter (DAT) were quantitatively analyzed to show dopaminergic neuronal dopamine secretion/activity/metabolism. Motor performance was evaluated by rotarod test weekly. Results demonstrated that the LpDNA-MBs (gene-liposome-MBs) complexes successfully serve as gene carrier and BBB-opening catalyst, and outperformed the separated LpDNA/MBs administration both in terms of gene delivery and expression. TH-positive IHC and measurement of DA and its metabolites DOPAC and HVA confirmed improved neuronal function, and the proposed system also provided the best neuroprotective effect to retard the progression of motor-related behavioral abnormalities. Immunoblotting and histological staining further confirmed the expression of reporter genes in neuronal cells. This study suggests that FUS exposures with the administration of LpDNA-MBs complexes synergistically can serve as an effective gene therapy strategy for MPTP-animal treatment, and may have potential for further application to perform gene therapy for neurodegenerative disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Strong absorption of femtosecond laser pulses in Au nano-colloidal suspensions was used to generate coherent ultrasound signals at 1-20 MHz frequency range. The most efficient ultrasound generation was observed at negative chirp values and was proportional to the pulse duration. Maximization of a dimensionless factor A ≡ αc 0 tp defined as the ratio of pulse duration tp and the time required for sound at speed c 0 to cross the optical energy deposition length (an inverse of the absorption coefficient α) given by 1/(αc 0 ). Chirp controlled pulse duration allows effective enhancement of ultrasound generation at higher frequencies (shorter wavelengths) and is promising for a high spatial resolution acoustic imaging.

Burst-tone focused ultrasound exposure in the presence of microbubbles has been demonstrated to be effective at inducing temporal and local opening of the blood-brain barrier (BBB), which promises significant clinical potential to deliver therapeutic molecules into the central nervous system (CNS). Traditional contrast-enhanced imaging confirmation after focused ultrasound (FUS) exposure serves as a post-operative indicator of the effectiveness of FUS-BBB opening, however, an indicator that can concurrently report the BBB status and BBB-opening effectiveness is required to provide effective feedback to implement this treatment clinically. In this study, we demonstrate the use of subharmonic acoustic emission detection with implementation on a confocal dual-frequency piezoelectric ceramic structure to perform real-time monitoring of FUS-BBB opening. A confocal dual-frequency (0.55 MHz/1.1 MHz) focused ultrasound transducer was designed. The 1.1 MHz spherically-curved ceramic was employed to deliver FUS exposure to induce BBB-opening, whereas the outer-ring 0.55 MHz ceramic was employed to detect the subharmonic acoustic emissions originating from the target position. In stage-1 experiments, we employed spectral analysis and performed an energy spectrum density (ESD) calculation. An optimized 0.55 MHz ESD level change was shown to effectively discriminate the occurrence of BBB-opening. Wideband acoustic emissions received from 0.55 MHz ceramics were also analyzed to evaluate its correlations with erythrocyte extravasations. In stage-2 real-time monitoring experiments, we applied the predetermined ESD change as a detection threshold in PC-controlled algorithm to predict the FUS exposure intra-operatively. In stage-1 experiment, we showed that subharmonic ESD presents distinguishable dynamics between intact BBB and opened BBB, and therefore a threshold ESD change level (5.5 dB) can be identified for BBB-opening prediction. Using this ESD change threshold detection as a surrogate to on/off control the FUS exposure in stage-2 experiments, we demonstrated both excellent sensitivity (92%) and specificity (92.3%) in discriminating BBB-opening occurrence can be obtained in animal treatments, while concurrently achieving a high positive predicted value (95.8%). Wideband ESD was also highly correlated with the occurrence and level of erythrocyte extravasations (r (2)  =  0.81). The proposed system configuration and corresponding analysis based on subharmonic acoustic emissions has the potential to be implemented as a real-time feedback control structure for reliable indication of intact FUS-BBB opening for CNS brain drug delivery.

In this study, a chemical oxidation method was employed to fabricate coral-like Cu2O nano/microstructures on Cu foils as counter electrodes (CEs) for dye-sensitized solar cells (DSSCs). The Cu2O nano/microstructures were prepared at various sintering temperatures (400, 500, 600 and 700 °C) to investigate the influences of the sintering temperature on the DSSC characteristics. First, the Cu foil substrates were immersed in an aqueous solution containing (NH4)2S2O8 and NaOH. After reacting at 25 °C for 30 min, the Cu substrates were converted to Cu(OH)2 nanostructures. Subsequently, the nanostructures were subjected to nitrogen sintering, leading to Cu(OH)2 being dehydrated into CuO, which was then deoxidized to form coral-like Cu2O nano/microstructures. The material properties of the Cu2O CEs were comprehensively determined using a scanning electron microscope, energy dispersive X-ray spectrometer, X-ray diffractometer, Raman spectrometer, X-ray photoelectron spectroscope, and cyclic voltameter. The Cu2O CEs sintered at various temperatures were used in DSSC devices and analyzed according to the current density-voltage characteristics, incident photon-to-current conversion efficiency, and electrochemical impedance characteristics. The Cu2O CEs sintered at 600 °C exhibited the optimal electrode properties and DSSC performance, yielding a power conversion efficiency of 3.62%. The Cu2O CEs fabricated on Cu foil were generally mechanically flexible and could therefore be applied to flexible DSSCs.

A novel magnetically guidable nanobubble is designed for disrupting the blood-brain barrier (BBB) by combining magnetic guidance with focused ultrasound in vivo. The magnetic-nanobubble platform also demonstrates the potential to serve as a unique theranostic tool via performing focused ultrasound (FUS)-induced BBB disruption and magnetic resonance imaging (MRI)/ultrasound dual-modality contrast-agent imaging to improve the drug delivery of therapeutic substances or gene therapy into the central nervous system., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two D-π-A'-A regioisomers (A-IDT-D and D-IDT-A) featuring 4,4'-di-p-tolyl-4 H-indeno[1,2-b]-thiophene as a π linker (π) between the diarylamino donor (D) and the pyrimidine-cyanoacrylic acid acceptor (A'-A) have been successfully synthesized and characterized as efficient sensitizers for the dye-sensitized solar cells (DSSCs). The different arrangements of the D and A'-A blocks on the unsymmetrical indenothiophene (IDT) core render the dipole of IDT being along (A-IDT-D) or opposite (D-IDT-A) to the direction of intramolecular (donor-to-acceptor) charge transfer, and thus induce variations in the physical properties. The experimental observations correlated well with the theoretical analyses, clearly revealing the trade-off between the molar extinction coefficient (ε) and the S0 →S1 transition energy. As a result, a superior ε value was observed for D-IDT-A, whereas a bathochromic shift in the absorption occurred in A-IDT-D. The larger ε value of D-IDT-A together with its more favorable energy level relative to TiO2 led to a higher power conversion efficiency of 7.41 % for the D-IDT-A-based DSSC, retaining approximately 95 % of the N719-based DSSC efficiency. This work manifests the clear structure-property relationship for the case of donor and acceptor components being connected by an unsymmetrical π linker and provides insights for molecular engineering of organic sensitizers., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new synthetic strategy for indolo[2,3-b]carbazole via a double-intramolecular Buchwald-Hartwig reaction has been established. The N-alkylated indolo[2,3-b]carbazole then was adopted as the geometry-fixed core for the synthesis of a new molecule (ICZDTA) bearing two bithiophene π-bridged 2-cyanoacrylic acid groups as the bidentate anchor. The bidentate anchoring together with efficient HOMO (indolo[2,3-b]carbazole) → LUMO (TiO2 nanocluster) electron transfer leads to the successful development of ICZDTA-based DSSC with a power conversion efficiency of 6.02%.

Lead is a renal toxin, and susceptibility to lead varies between individuals. Metallothionein (MT) is known for its metal scavenging role. The aim of the study was to investigate the association of blood lead levels, urinary uric acid (UA) and N-acetyl-beta-d-glucosaminidase (NAG) in chronic occupational lead-exposed workers, and to study whether the association was influenced by MT1A gene polymorphisms. In this cross-sectional study, 412 lead-exposed workers participated. Their annual health examination data and renal function markers were collected after the Institutional Review Broad of Kaohsiung Medical University Hospital approved the study and consent letters were obtained. From the blood samples, DNA was extracted and used for real-time PCR typing of 2 MT1A single nucleotide polymorphisms (SNPs): rs11640851 and rs8052394 on exons 2 and 3. Descriptive analysis, one-way ANOVA, and multiple linear regressions were performed. There was a significant inverted relationship of creatinine-adjusted urine UA concentrations and the time-weighted index of cumulative blood lead levels (TWICL) that may be significantly influenced by the AC genotypes of rs11640851 in exon 2 and rs8052394 in exon 3. After controlling for potential confounding factors, the creatinine-adjusted urine NAG concentrations were shown to be influenced by the GG genotype of rs8052394 in exon 3, and were weakly increased with TWICL. Therefore, we concluded that the variations of MT1A SNPs may influence urine UA and NAG excretion in chronic lead-exposed workers, and urine creatinine-adjusted urine UA as a biomarker of lead toxicity should be considered., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

An amine-free oligothiophene-based dye (BTB) featuring a tailor-made dianchoring function, a spiro-configured central unit, and bulky end-capping TIPS groups to diminish intermolecular interactions and to suppress aggregation-induced self-quenching was synthesized to achieve efficient dye-sensitized solar cells with a high power conversion efficiency of 6.52%.

A series of new organic dyes exploiting coplanar indacenodithiophene as the central π-spacer of the classical donor-(π-spacer)-acceptor configuration were synthesized and characterized for dye-sensitized solar cells. The coplanarity of the indacenodithiophene core facilitates efficient donor to acceptor charge transfer, imparting the new organic dyes significant bathochromic shifts and remarkable power conversion efficiencies of up to 6.7% (DTInDT) under AM 1.5G radiation.

Two new organic dyes adopting coplanar diphenyl-substituted dithienosilole as the central linkage have been synthesized, characterized, and used as the sensitizers for dye-sensitized solar cells (DSSCs). The best DSSC exhibited a high power conversion efficiency up to 7.6% (TP6CADTS) under AM 1.5G irradiation, reaching approximately 96% of the ruthenium dye N719-based reference cell under the same conditions.

One primary focus of the present study was to clarify the crucial resorption-location relationship of a recently developed single-phase TTCP-derived calcium phosphate cement (CPC) implanted in rabbit femur in a systematic and quantitative way. Gross examination of retrieved CPC/bone composite samples indicated that the CPC implant did not evoke inflammatory response, necrosis or fibrous encapsulation in surrounding bony tissues. Histological examination revealed excellent CPC-host bone bonding. At 4 weeks, the resorption-induced voids between terminals of bone defects and implants were largely filled with new bone. CPC resorption, new blood vessels, osteocytes, osteons and osteoblast-like cells lining up with active new bone were observed at remodeling sites. At 12 weeks, a new bone network was developed within femoral defect, while CPC became islands incorporated in the new bone. At this stage, crevices filled with lamellar new bone structure were frequently observed. At 24 weeks, bone ingrowth and remodeling activities became so extensive that the interface between residual cement and new bone became less identifiable. In general, at all implant locations the resorption ratio values increased with implantation time, while at all implantation times the resorption ratios decreased from the exterior (cortical site) to the interior (cancellous site) of implants. At the end of 24 weeks, CPC was almost completely resorbed and bone remodeling almost finished at the cortical site.

A risk-based inspection system and a piping inspection guideline model were developed in this study. The research procedure consists of two parts--the building of a risk-based inspection model for piping and the construction of a risk-based piping inspection guideline model. Field visits at the plant were conducted to develop the risk-based inspection and strategic analysis system. A knowledge-based model had been built in accordance with international standards and local government regulations, and the rational unified process was applied for reducing the discrepancy in the development of the models. The models had been designed to analyze damage factors, damage models, and potential damage positions of piping in the petrochemical plants. The purpose of this study was to provide inspection-related personnel with the optimal planning tools for piping inspections, hence, to enable effective predictions of potential piping risks and to enhance the better degree of safety in plant operations that the petrochemical industries can be expected to achieve. A risk analysis was conducted on the piping system of a petrochemical plant. The outcome indicated that most of the risks resulted from a small number of pipelines.

The purpose of the present study was to investigate the gamma-radiation effect on the structure and properties of the single-phase tetracalcium phosphate (TTCP) powder and its derived calcium phosphate cement (CPC). Experimental results show that low-dosed (0-30 kGy) CPC has a setting time of 10-12 min, while high-dosed (40-120 kGy) CPC has a setting time of 8-10 min. The low dose gamma-radiation does not significantly change porosity volume fraction or compressive strength of the CPC. The pH values of all CPC samples fell in a relatively narrow band, with a band width of 8.5-9.1 (in terms of pH value). With a dose of 10 or 20 kGy gamma-radiation, the TTCP-apatite conversion ratio does not change much. With 30 kGy the conversion ratio significantly increases and reaches a maximum value. With further increases in dose, the conversion ratio quickly declines. With increasing gamma-ray dose, the CPC morphology becomes more porous/loose and apatite particles become larger in size. When exposed to a high dose (120 kGy) of gamma-radiation, TTCP structure is radiation-damaged, and gamma-ray-induced formation of apatite is confirmed by transmission electron microscopic/selected-area diffraction/lattice imaging analyses., (2006 Wiley Periodicals, Inc.)

We have synthesized a new green fluorescent dopant C-545P having incorporated five strategically placed "methyl" steric spacers on the julolidyl ring system. C-545P has good thermal properties and photostability, and when fabricated as a dopant in an Alq(3)-hosted OLED device, it shows notable improvement in luminance efficiency and is more resistant to concentration quenching than C-545T, particularly in the doping concentration range between 1 and 2% v/v, while achieving comparable device stability. [structure: see text]