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Chronic subdural hematoma (CSDH) is one of the most common neurological disorders. In recent years, atorvastatin (ATV) combined with dexamethasone (DXM) has been proved to be a more efficacious therapy in treating patients with CSDH than ATV monotherapy. To investigate whether DXM has an effect on the pharmacokinetics of ATV, the expression of organic anion transport polypeptides 1B1 (OATP1B1) and upstream nuclear receptors liver X receptor α (LXRα) in rat liver and HepG2 cells were evaluated. The results showed that when DXM was combined with ATV, the area under curve (AUC(0~∞)) of ATV, o-ATV and p-ATV was increased by 1.550, 1.420, 1.676 times, respectively. In HepG2 cells, DXM inhibited the uptake of ATV by 59.24%. Also, DXM decreased the expression of OATP1B1 and LXRα both in the rat liver and HepG2 cells. Dual-luciferase reporter assay indicated that DXM had an inhibitory effect on the LXRα-OATP1B1 pathway. In conclusion, DXM downregulated the protein expression of OATP1B1 by inhibiting the LXRα-OATP1B1 pathway, thus, decreasing hepatic drug uptake and increasing plasma concentration of ATV and its active metabolites.

In this letter, we demonstrate a reconfigurable logic-memory hybrid device (R-LMHD), which can be dynamically and reversibly switched between the logic- and memory- mode. The logic-mode device exhibits a $2.5\times 10^{6}$ ON/ OFF current ratio and nearly zero hysteresis, which indicates the weak influence of defects trapping and de-trapping. The memory-mode device shows a large memory window up to 2.19 V and the window maintains up to 1.44 V after 106 program/erase cycles. The excellent performance can be attributed to the high crystalline quality of ferroelectric Hf0.5Zr0.5O2 (HZO) and the insertion of internal metal gate (IMG) between HZO and dielectric layer. Such R-LMHD features run-time tuning of threshold voltage and hysteresis, electrically reconfigurable. Furthermore, the subthreshold swing ( SS ) is electrically tunable with a minimum SS ( $SS_{min}$ ) of 35 mV/decade and a maintainability of sub-60 mV/decade about 3 orders. The R-LMHD provides a promising way to realize future in-memory computing and low power consumption applications.

Dimetridazole (DTZ) is such a significant indicator in food safety assessment that a high priority should be given to it. In this work, a novel three-dimensional Metal-Organic Framework zwitterionic composite, {[CdL2]·Cl2·6H2O} (MOF 1), was synthesized by hydrothermal method and applied as a fluorescence probe for the detection of DTZ. Several crucial factors of the obtained MOF 1, such as structure stability, fluorescence properties, selectivity, sensitivity and reproducibility, were studied in detail. A series of sensing investigations demonstrate extremely specific and ultrafast detection of DTZ via a conspicuous fluorescence quenching (Ksv=8.1374 × 104 M− 1) from MOF 1 under the optimized conditions. The linear range for quantitative detection of DTZ was 0.0 µM ~ 40.0 µM with a low limit of detection of 0.012 µM. The fluorescence quenching mechanisms have been explained, being caused by a combination of both competitive absorption and photoinduced electron transfer. DTZ in milk, honey, tap and lake water were successfully determined by this fluorescence probe with quick response, and the recovery rates are 97.4%∼102.6%, which indicates MOF 1 having a tremendous application prospect in the detection of DTZ in food and environmental samples.

A self-powered sensor for the collection and monitor of body motion mechanical energy is manufactured. This sensor is made up of PVDF which is dealt with polarization. According to practical needs, single or multiple sensors could be selected to serve the function. Through piezoelectric voltage signal that produced by tester body motion mechanical energy to achieve body motion monitor and energy collection to charge microelectronic equipment. This kind of study can help collect body motion energy, facilitate sports training, guide exercise rehabilitation, and promote evaluation of human movement ability to prevent potential risks such as falls. It provides new ideas to material science and sports science practical application.

The discovery of ferroelectricity in hafnium zirconium oxide (HZO) thin films has attracted wide attention from academia to industry due to the application in ferroelectric non-volatile random access memories (FeRAM) with prominent performance in scalability and CMOS process compatibility. Dielectric behavior of ferroelectric HZO thin films is a key factor affecting the dynamic effect, piezoelectric and electrostrictive effect. Interface between HZO and capping electrodes plays an important role in regulating the dielectric properties. In this paper, the impedance frequency response and dielectric spectrum of ferroelectric HZO thin films were analyzed. Parameters of the interface were extracted to analyze the regulating effect on the dielectric properties based on an impedance model with constant phase element (CPE). Besides, dielectric spectrums at elevated temperatures were identified to verify this analysis.

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity worldwide. Tools available for diagnosis and therapy are limited. Small extracellular vesicle (sEV) microRNAs (miRNAs) play an important role in TBI disease progression. This study aimed to investigate the alterations in sEV miRNAs expression in the mouse brain extracellular space after TBI. Twenty-four C57BL/6J mice were randomly divided into two groups (12/group). The TBI group was subjected to all surgical procedures and fluid percussion injury (FPI). The sham group only underwent surgery. Brain specimens were collected 3 h after TBI/sham. The brain sEV were isolated. Differentially expressed miRNAs were identified. A total of 50 miRNAs were observed to be differentially expressed (fold change ≥1.5 and P0.05) after TBI, including 5 upregulated and 45 downregulated. The major enriched Gene Ontology terms were metabolic processes, cell, intracellular, organelle, cytoplasm, axon, binding, protein kinase activity, protein binding, and protein dimerization activity. The KEGG pathway analysis predicted that the pathways affected by the variation of miRNAs in sEVs after TBI included the Wnt signaling pathway and NF-κB signaling pathway. The changes in five miRNAs were confirmed by qRT-PCR. In conclusion, this study demonstrated the differential expression of a series of miRNAs in brain sEV after TBI, which might be correlated with post-TBI physiological and pathological processes. The findings might also provide novel targets for further investigating the molecular mechanisms underlying TBI and potential therapeutic interventions.

Background and purpose We develop a method of imaging exosomes in vivo according to the vital role of exosomes in intercellular communication. This study aims to design a new label method that allows the visualization of labeled exosomes with magnetic resonance imaging (MRI). Methods We designed a fusion protein consisting of two parts, namely, ferritin heavy chain (FTH1) and a truncated lactadherin. FTH1 is used as an MRI reporter. Lactadherin is a trans-membrane protein. The lactadherin protein are mostly located on the outer surface of exosomes. We replaced the outer membrane part of lactadherin with FTH1, infected mesenchymal stem cells with lentivirus carrying the fusion protein, and isolated exosomes from the labeled cells by ultracentrifugation. Labeled exosomes were validated by transmission electron microscopy images, Western blot, nanosight particle tracking, and visualized in vitro and in vivo by MRI. Results FTH1 expression would suppress mesenchymal stem cell proliferation, whereas the characterization of labeled exosomes remains comparable with unlabeled exosomes. MR imaging shows that exosomes labeled with FTH1 can be visualized in vitro and in vivo. Conclusion This innovative reporter–imaging approach to track and visualize exosomes with MRI can be utilized as a tool for the study of the role of exosomes under different conditions.

Background Numerous studies demonstrated that exosomes play a powerful role in mediating intercellular communication to induce a pro-tumoral environment to promote tumor progression, including pre-metastatic niche formation and metastasis. Noninvasive imaging could determine the in vivo kinetics of exosomes in real time to provide better understanding of the mechanisms of the tumor formation, progression and metastasis. Magnetic resonance imaging (MRI) is an ideal technique which provides excellent anatomical resolution, intrinsic soft tissue contrast, unlimited penetration depth and no radiation exposure. Methods A fusion protein composed of ferritin heavy chain (FTH1) and lactadherin was designed for visualizing exosomes through MRI. FTH1 was served as MRI reporter protein and lactadherin is a membrane-associated protein that is distributed on exosome surface. The characterizations of labeled exosomes were validated through transmission electron microscopy, western blot, nanoparticle tracking analysis and finally visualized in vitro and in vivo through MRI. Results MR imaging showed that the labeled exosomes are able to be visualized in vitro and in vivo. Verification of the characterizations of exosomes observed no significant difference between labeled and unlabeled exosomes. Conclusion The proposed FTH1 labeling method was useful for visualizing exosomes through MRI. General significance The present study first reported a novel self-label method for imaging labeled exosomes of tumor cells in vivo through MR with cell endogenous MRI reporter protein. It may be further used as a tool to enhance understanding the role of exosomes in various pathophysiological conditions.

A ferroelectric HfZrO-based synaptic transistor with multi-state plasticity was demonstrated. The bottom-gated TiN/HfZrO/α-InGaZnO structure was utilized. In this device, accurate control of the polarization state in the ferroelectric HfZrO gate by the applied voltage could induce conductance modulation in channel, so that the multi-state plasticity of a neuron synapse could be mimicked. This device exhibited typical anticlockwise ferroelectric hysteresis window of 1 V, ~105on/off current ratio, and 100 mV/dec subthreshold slope. An analog synaptic 20-state plasticity including potentiation and depression was observed with optimizable linearity and high dynamic ratio $(> \mathbf{10}^{\mathbf{2}})$ at room temperature as the result of conductance modulation.

PURPOSE: This study was performed to introduce an in vivo hybrid multimodality technique involving the coregistration of micro-computed tomography (micro-CT) and high-resolution magnetic resonance imaging (HR-MRI) to concomitantly visualize and quantify mineralization and vascularization at follow-up in a rat model. MATERIALS AND METHODS: Three adult female rats were randomly assigned as test subjects, with 1 rat serving as a control subject. For 20 weeks, the test rats received a weekly intravenous injection of 30 µg/kg zoledronic acid, and the control rat was administered a similar dose of normal saline. Bilateral extraction of the lower first and second molars was performed after 10 weeks. All rats were scanned once every 4 weeks with both micro-CT and HR-MRI. Micro-CT and HR-MRI images were registered and fused in the same 3-dimensional region to quantify blood flow velocity and trabecular bone thickness at T0 (baseline), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks), T16 (16 weeks), and T20 (20 weeks). Histological assessment was the gold standard with which the findings were compared. RESULTS: The histomorphometric images at T20 aligned with the HR-MRI findings, with both test and control rats demonstrating reduced trabecular bone vasculature and blood vessel density. The micro-CT findings were also consistent with the histomorphometric changes, which revealed that the test rats had thicker trabecular bone and smaller marrow spaces than the control rat. CONCLUSION: The combination of micro-CT and HR-MRI may be considered a powerful non-invasive novel technique for the longitudinal quantification of localized mineralization and vascularization. ispartof: IMAGING SCIENCE IN DENTISTRY vol:50 issue:3 pages:199-208 ispartof: location:Korea (South) status: published

OBJECTIVE: To investigate the effects of millimeter wave (MMW) exposure on apoptosis of human melanoma A375 cells and explore the mechanisms. METHODS: Through electromagnetic field calculation we simulated MMW exposure in cells and calculated the specific absorption rate (SAR). The optimal irradiation parameters were determined according to the uniformity and intensity of the SAR. A375 cells were then exposed to MMV for 15, 30, 60, or 90 min, with or without pretreatment with the caspase-3 inhibitor AC-DEVD-fmk (10 μmol/L) for 1 h at 90 min before the exposure. CCK-8 assay was used to assess the changes in the viability and Annexin-V/ PI staining was used to detect the apoptosis of the cells following the exposures; Western blotting was used to detect the expression of caspase-3 in the cells. RESULTS: The results of electromagnetic field calculation showed that for optimal MMV exposure, the incident field needed to be perpendicular to the bottom of the plastic Petri dish with the antenna placed below the dish. CCk-8 assay showed that MMW exposure significantly inhibited the cell viability in a time-dependent manner (P < 0.05); exposures for 15, 30, 60, and 90 min all resulted in significantly increased apoptosis of the cells (P < 0.05). The cells with MMW exposure showed significantly increased expression of caspase-3. The inhibitory effect of MMW on the cell viability was antagonized significantly by pretreatment of the cells with AC-DEVD-fmk (P < 0.05), which increased the cell viability rate from (36.7±0.09)% to (59.8±0.06)% (P < 0.05). CONCLUSION: 35.2 GHz millimeter wave irradiation induces apoptosis in A375 cells by activating the caspase-3 protein.

Ferroelectric memories with ultralow‐power‐consumption are attracting a great deal of interest with the ever‐increasing demand for information storage in wearable electronics. However, sufficient scalability, semiconducting compatibility, and robust flexibility of the ferroelectric memories remain great challenges, e.g., owing to Pb‐containing materials, oxide electrode, and limited thermal stability. Here, high‐performance flexible nonvolatile memories based on ferroelectric Hf0.5Zr0.5O2 (HZO) via quasi‐van der Waals heteroepitaxy are reported. The flexible ferroelectric HZO exhibits not only high remanent polarization up to 32.6 µC cm−2 without a wake‐up effect during cycling, but also remarkably robust mechanical properties, degradation‐free retention, and endurance performance under a series of bent deformations and cycling tests. Intriguingly, using HZO as a gate, flexible ferroelectric thin‐film transistors with a low operating voltage of ±3 V, high on/off ratio of 6.5 × 105, and a small subthreshold slope of about 100 mV dec−1, which outperform reported flexible ferroelectric transistors, are demonstrated. The results make ferroelectric HZO a promising candidate for the next‐generation of wearable, low‐power, and nonvolatile memories with manufacturability and scalability., Flexible quasi‐van der Waals hafnium‐based oxides are fabricated and investigated systematically. Due to high remanent polarization, robust mechanical properties, and degradation‐free retention and endurance, the nonvolatile memories based on ferroelectric capacitors and thin‐film transistors show excellent performance and mechanical durability, which outperform reported flexible ferroelectric devices. The findings provide a pathway for wearable nonvolatile memories with manufacturability and scalability.

To explore the effect of the ZrO2 content on the switching speed of ferroelectric HfO2-ZrO2 (FE-HZO), we demonstrate 10 nm FE-HZO capacitors fabricated with 5:5, 6:4, and 7:3 HfO2 and ZrO2 atomic-layer-deposition-cycling ratios. The FE-HZO devices show high remanent polarization (Pr) of 26, 20, and 11 μC/cm2 for the 5:5, 6:4, and 7:3 samples, respectively. The FE-HZO capacitors with lower ZrO2 contents show increasing coercive fields, which intuitively seem to increase switching difficulty. However, the FE-HZO devices with 50 mol. %, 40 mol. %, and 30 mol. % ZrO2 contents show decreasing switching times for 80% polarization, namely, 1.2, 0.9, and 0.7 μs, respectively. Because of the polycrystalline nature of FE-HZO, the distribution of local fields in the film is analyzed based on the inhomogeneous field mechanism model. The results show that the FE-HZO devices with lower ZrO2 contents have higher active fields and less uniform distribution of local fields. However, time constants for the 5:5, 6:4, and 7:3 samples decrease dramatically, being 137, 98, and 14 ps, respectively. These results unveil the distribution of the local fields in FE-HZO with varying ZrO2 contents and are helpful for understanding and optimizing the switching dynamics of FE-HZO for non-volatile memory applications.

The discovery of HfO2-based ferroelectric (FE) films gives FE memory devices great potential for the next-generation memory technology. In this letter, TiNx with varying nitrogen atomic contents was demonstrated as electrodes of FE Hf0.5Zr0.5O2 memory devices on quartz substrates for transparent memory applications. The transmittance and reflectance from 350 nm to 2500 nm of the TiNx/Hf0.5Zr0.5O2/TiNx structures generally increased and decreased, respectively. Selectivity between the visible and infrared light altered as the N content is increased. When the N2 ratio increases from 0% to 30%, the transmittance selectivity between 1064 nm (infrared) and 532 nm (green) lights increases from 79.6% to 105.3%, while the reflectance selectivity decreases from 107.9% to 48.9%. The polarization cycling performance of FE TiNx/Hf0.5Zr0.5O2/TiNx was explored up to 107 times. The devices with N-rich TiNx electrodes showed suppression of the wake-up effect during cycling. The transient current loops and atomic-fraction depth profiles of capacitors were inspected as well. The results indicated that there were fewer oxygen-vacancy defects in the as-grown N-rich devices and no influential redistribution of oxygen-vacancy defects during the cycling.

This paper presents the concept of self-propelled magnetoelastic (ME) biosentinels that seek out and capture pathogenic bacteria in stagnant liquids. These biosentinels are composed of a free-standing, asymmetric-shaped ME resonator coated with a filamentous landscape phage that specifically binds with a pathogen of interest. When a time-varying magnetic pulse is applied, the ME biosentinels can be placed into mechanical resonance by magnetostriction. The resultant asymmetric vibration then generates a net force on the surroundings and hence generates autonomous motion in the liquid. As soon as the biosentinels find and bind with the target pathogen through the phage-based biomolecular recognition, a change in the biosentinel’s resonant frequency occurs, and thereby the presence of the target pathogen can be detected. In order to actuate the ME biosentinels into mechanical resonance of a desired mode, modal analysis using the three-dimensional finite element method was performed. In addition, the design of a magnetic chamber that can control the orientation and/or translation of a biosentinel is discussed.

Phage-based magnetoelastic (ME) biosensors have proven useful in rapidly and inexpensively detecting food surface con- tamination. These biosensors are wireless, mass-sensitive biosensors and can be placed directly on food surfaces to detect the presence of target pathogens. Previously, millimeter-scale strip-shaped ME biosensors have been used to demonstrate direct detection of Salmonella Typhimurium on various fresh produce surfaces, including tomatoes, shell eggs, watermel- ons, and spinach leaves. Since the topography of these produce surfaces are different, and the biosensor must come into direct contact with Salmonella bacteria, food surfaces with large roughness and curvatures (e.g., spinach leaf surfaces) may allow the bacteria to avoid direct contact, thereby avoiding detection. The primary objective of this paper is, hence, to investigate the effects of food surface topography on the detection capabilities of the biosensors. Spinach leaf surfaces were selected as model surfaces, and detection experiments were conducted with differently sized biosensors (2 mm, 0.5 mm, and 150 μm in length). Spinach leaf roughness and curvatures of both adaxial (top) and abaxial (underside) surfaces were measured using a confocal laser scanning microscope. The experimental results showed that in spinach as the sen- sor was made smaller, the physical contact between the biosensors and bacteria were improved. Smaller sensors thereby enhance detection capabilities. When proper numbers of biosensors are used, micron-scale biosensors are anticipated to yield improved limits of detection over previously investigated millimeter-scale biosensors.

This paper investigates the use of self-propelled magnetoelastic (ME) biosentinels to seek out and capture pathogenic bacteria in a stagnant liquid. These ME biosentinels are composed of an asymmetric-shaped ME resonator coated with a filamentous landscape phage that specifically binds with a pathogen of interest. When a time-varying magnetic pulse is applied, the ME biosentinels can be placed into mechanical resonance by magnetostriction. The resultant asymmetric vibration then generates a net force on the surroundings and hence generates autonomous motion in the liquid. As soon as the biosentinels find and bind with the target pathogen through the phage-based biomolecular recognition, a change in the biosentinel’s resonant frequency occurs, and thereby the presence of the target pathogen can be detected. In order to actuate the ME biosentinels into mechanical resonance of a desired mode, modal analysis using the three-dimensional finite element method was first performed, and the resonant frequency was determined. In addition, the net force due to the asymmetric vibration was calculated, and the resultant motion of the biosentinels was simulated. Both dynamic simulation and experimental results showed that the ME biosentinels can move autonomously through the liquid and actively bind with the target pathogen.

This study presents results from an investigation into the rapid, sensitive, real-time direct detection of Salmonella Typhimurium on food surfaces. The biosensor consists of a freestanding, strip-shaped magnetoelastic (ME) resonator as the signal transducer and E2 phage as the bio-molecular recognition element that selectively binds with S. Typhimurium (1). The ME resonator is a class of mass-sensitive biosensor that can be wirelessly actuated into mechanical resonance by an externally applied time-varying magnetic field (2). When the biosensor binds with S. Typhimurium, the mass of the sensor increases, resulting in a decrease in the sensor's resonant frequency (3). We have previously reported the possible use of ME biosensors for the detection of pathogenic bacteria on food surfaces (4). This new detection system consists of a planar spiral coil that excites and measures the resonant frequency of freestanding ME biosensors on the surface of fruits and vegetables (5). Multiple E2 phage-coated biosensors (measurement sensors) were placed on the food surfaces spiked with S. Typhimurium of various concentrations. Control sensors without phage were also used to compensate for environmental effects and non-specific binding. During binding with the bacteria, the resonant frequency of the sensor was wirelessly measured in real time. This frequency change is directly proportional to the mass of the bacteria bound to the sensor surface. References S. Horikawa, D. Bedi, S. Li, W. Shen, S. Huang, I. Chen, Y. Chai, M. L. Auad, M. J. Bozack, J. M. Barbaree, V. A. Petrenko, and B. A. Chin, 2011. Biosensors and Bioelectronics, Vol. 26(5), 2361-2367. Y. Chai, H. C. Wikle, Z. Wang, S. Horikawa, S. Best. Z. Cheng, D. F. Dyer and B. A. Chin, 2013. Journal of Applied Physics, Vol. 114, 104504. Y. Chai, S. Li, S. Horikawa, M. Park, V.J. Vodyanoy and B. A. Chin. 2012. Journal of Food Protection, Vol. 75(4), 631-636. Y. Chai, S. Horikawa, H. C. Wikle, Z. Wang and B. A. Chin, 2013. Applied Physics Letters, Vol. 103, 173510. Y. Chai, S. Horikawa, S. Li, H. C. Wikle, and B. A. Chin, 2013. Biosensor and Bioelectronics, Vol. 50, 311-317.