Achieving an improved understanding of catalyst properties, with ability to predict new catalytic materials, is key to overcoming the inherent limitations of metal oxide based gas sensors associated ...with rather low sensitivity and selectivity, particularly under highly humid conditions. This study introduces newly designed bimetallic nanoparticles (NPs) employing bimetallic Pt‐based NPs (PtM, where M = Pd, Rh, and Ni) via a protein encapsulating route supported on mesoporous WO3 nanofibers. These structures demonstrate unprecedented sensing performance for detecting target biomarkers (even at p.p.b. levels) in highly humid exhaled breath. Sensor arrays are further employed to enable pattern recognition capable of discriminating between simulated biomarkers and controlled breath. The results provide a new class of multicomponent catalytic materials, demonstrating potential for achieving reliable breath analysis sensing.
Effective strategy to readily synthesize highly dispersed Pt‐based bimetallic (PtM, where M = Pd, Rh, and Ni) NPs as a new class of active catalysts is successfully developed on the highly porous architecture of 1D WO3 nanofibers via a protein template, i.e., apoferritin, in combination with the electrospinning method for superior exhaled‐breath sensors.
Few-layer black phosphorus (BP), also known as phosphorene, is poised to be the most attractive graphene analogue owing to its high mobility approaching that of graphene, and its thickness-tunable ...band gap that can be as large as that of molybdenum disulfide. In essence, phosphorene represents the much sought after high-mobility, large direct band gap two-dimensional layered crystal that is ideal for optoelectronics and flexible devices. However, its instability in air is of paramount concern for practical applications. Here, we demonstrate air-stable BP devices with dielectric and hydrophobic encapsulation. Microscopy, spectroscopy, and transport techniques were employed to elucidate the aging mechanism, which can initiate from the BP surface for bare samples, or edges for samples with thin dielectric coating, highlighting the ineffectiveness of conventional scaled dielectrics. Our months-long studies indicate that a double layer capping of Al2O3 and hydrophobic fluoropolymer affords BP devices and transistors with indefinite air-stability for the first time, overcoming a critical material challenge for applied research and development.
Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common ...NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
Mycobacterium abscessus (MAB) is a rapidly growing mycobacterium (RGM), and infections with this pathogen have been increasing worldwide. Recently, we reported that rough type (MAB-R) but not smooth ...type (MAB-S) strains enhanced type 1 interferon (IFN-I) secretion via bacterial phagosome escape, contributing to increased virulence. Here, we sought to investigate the role of mitochondrial oxidative stress in bacterial survival, IFN-I secretion and NLRP3 inflammasome activation in MAB-infected murine macrophages. We found that live but not heat-killed (HK) MAB-R strains increased mitochondrial ROS (mtROS) and increased release of oxidized mitochondrial DNA (mtDNA) into the cytosol of murine macrophages compared to the effects of live MAB-S strains, resulting in enhanced NLRP3 inflammasome-mediated IL-1β and cGAS-STING-dependent IFN-I production. Treatment of the infected macrophages with mtROS-modulating agents such as mito-TEMPO or cyclosporin A reduced cytosolic oxidized mtDNA, which inhibited the MAB-R strain-induced production of IL-1β and IFN-I. The reduced cytosolic oxidized mtDNA also inhibited intracellular growth of MAB-R strains via cytosolic escape following phagosomal rupture and via IFN-I-mediated cell-to-cell spreading. Moreover, our data showed that mtROS-dependent IFN-I production inhibited IL-1β production, further contributing to MAB-R intracellular survival in murine macrophages. In conclusion, our data indicated that MAB-R strains enhanced IFN-I and IL-1β production by inducing mtROS as a pathogen-associated molecular pattern (PAMP). These events also enhance bacterial survival in macrophages and dampen inflammation, which contribute to the pathogenesis of MAB-R strains.
In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with the aging population. Alzheimer's disease (AD) is one of the most commonly reported ...neurodegenerative disorders, and it is estimated to increase by roughly 30% among the aged population. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates - such as acetylcholinesterase inhibitors are currently utilized as an effective clinical therapy. However, targeted drug delivery of these drugs to the central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, and reduced efficiency due to the impediments of the blood-brain barrier (BBB). Current advances in nanotechnology present opportunities to overcome such limitations in delivering active drug candidates. Nanodrug delivery systems are promising in targeting several therapeutic moieties by easing the penetration of drug molecules across the CNS and improving their bioavailability. Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have been adapted to develop successful therapeutics with sustained release and improved efficacy. Here, we discuss few recently updated nano-drug delivery applications that have been adapted in the field of AD therapeutics, and future prospects on potential molecular targets for nano-drug delivery systems.
Abstract
Study Objectives
We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with ...video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD).
Methods
The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures.
Results
Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered “much or very much improved” on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman’s rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements).
Conclusions
Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.
Graphical Abstract
Ciliopathies are clinically overlapping genetic disorders involving structural and functional abnormalities of cilia. Currently, there are no small-molecule drugs available to treat ciliary defects ...in ciliopathies. Our phenotype-based screen identified the flavonoid eupatilin and its analogs as lead compounds for developing ciliopathy medication. CEP290, a gene mutated in several ciliopathies, encodes a protein that forms a complex with NPHP5 to support the function of the ciliary transition zone. Eupatilin relieved ciliogenesis and ciliary receptor delivery defects resulting from deletion of CEP290. In rd16 mice harboring a blinding Cep290 in-frame deletion, eupatilin treatment improved both opsin transport to the photoreceptor outer segment and electrophysiological responses of the retina to light stimulation. The rescue effect was due to eupatilin-mediated inhibition of calmodulin binding to NPHP5, which promoted NPHP5 recruitment to the ciliary base. Our results suggest that deficiency of a ciliopathy protein could be mitigated by small-molecule compounds that target other ciliary components that interact with the ciliopathy protein.
A thorough investigation of membranes as well as their transport and material properties is a key to understanding the governing principles and unresolved issues of membrane processes. Through ...molecular dynamics (MD) simulations, static and dynamic properties of membrane separation systems may be investigated on a molecular level. By reviewing over 70 articles, this paper aims to highlight the usefulness of applying molecular dynamics in membranes (MDM) in order to broaden our knowledge of membrane-based water treatment processes. Here, the theoretical foundations of classical MD are described together with the results that are obtainable from MDM simulations. By compiling results from published works, we emphasize the ability of MD to determine membrane transport and material properties from simulations. The authors conclude by suggesting the further use of MDM for prospective research areas pertaining to membrane-based water treatment processes.
•The basics of MD are summarized in the context of membrane-based water treatment.•Procedure for running MD simulations is presented together with obtainable results.•MD studies related to membrane-based water treatment processes are reviewed.•Membrane- and water-related research areas in which MD can be applied are suggested.•Using MD will allow deeper understanding of membrane-based water treatment systems.
Label-free biosensing methods that rely on the use of localized surface plasmon resonance (LSPR) have attracted great attention as a result of their simplicity, high sensitivity, and relatively low ...cost. However, in-situ analysis of real samples using these techniques has remained challenging because colloidal nanoparticles (NPs) can be unstable at certain levels of pH and salt concentration. Even in the case of a chip-type LSPR sensor that can resolve the instability problem by employing NPs immobilized on the substrate, loading of a sample to sensor chip with exact volume control can be difficult for unskilled users. Herein, we report an optical-fiber-based LSPR aptasensor that can avoid these problems and serve as a portable and simple system for sensitive detection of a small mycotoxin, ochratoxin A (OTA), in real samples. The optical fiber coated with aptamer-modified gold nanorods (GNRs) is simply dipped into a solution containing OTA and subjected to LSPR analysis. Quantitative analysis of OTA is performed by measuring the spectral red shift of the LSPR peak of GNRs. Under optimized conditions, the LSPR peak shift displays a linear response (R2 = 0.9887) to OTA in the concentration range from 10pM to 100nM, with a limit of detection of 12.0pM (3S). The developed sensor shows a high selectivity for OTA over other mycotoxins such as zearalenone (ZEN) and ochratoxin B (OTB), and shows an accurate detection capability for OTA in real grape juice samples.
•Simple and in situ measurement of OTA was possible by dipping a sensing probe into solution samples.•Wide dynamic range from 10pM to 100nM was achieved.•Limit of detection (LOD) for OTA was reached to 12.0pM (3S).•OTA in grape juice could be successfully analyzed with good recoveries.
We present a compact, filtering power divider (FPD) using integrated passive device technology (IPD) for mm‐wave applications. Our proposed FPD design integrates quarter‐wavelength coupled‐resonator ...bandpass filters with a Wilkinson power divider, using size reduction techniques. Coupled coplanar waveguides provide excellent coupling while occupying a small area, and metal‐insulator‐metal capacitors offer the required λ/4 phase shift without length extension. The center frequency of the filtering power divider/combiner (FPD/C) is located at 30‐GHz. We demonstrate our FPD design by fabricating four prototypes with parameter variations. The insertion loss, fractional bandwidth, and size of the FPD/C designed in this study are from 2.56 to 3.3 dB, from 9.67% to 19.4%, and from 0.592 to 0.220‐mm2, respectively. In addition, the return loss of all models at the center frequency is 28.5 dB or more, and the isolation is 16.6 dB or more.
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