Abstract
We report an EN2-specific (
K
d
= 8.26 nM) aptamer, and a sensitive and specific enzyme-linked oligonucleotide assay (ELONA) for rapid and sensitive colorimetric detection of bladder and ...prostate cancer biomarker EN2 in urine. The assay relies on an aptamer-mediated hybridization chain reaction (HCR) to generate DNA nanostructures that bind to EN2 and simultaneously amplify signals. The assay can be performed within 2.5 h, and has a limit of detection of 0.34 nM in buffer and 2.69 nM in artificial urine. Moreover, this assay showed high specificity as it did not detect other urinary proteins, including biomarkers of other cancers. The proposed ELONA is inexpensive, highly reproducible, and has great chemical stability, so it may enable development of a simple, sensitive and accurate diagnostic tool to detect bladder and prostate cancers early.
One of the central questions about the cognitive neuroscience of creativity is the extent to which creativity depends on either domain-specific or domain-general mechanisms. To address this question, ...we carried out two parallel activation likelihood estimation meta-analyses of creativity: 1) a motoric analysis that combined studies across five domains of creative production (verbalizing, music, movement, writing, and drawing), and 2) an analysis of the standard ideational task used to study divergent thinking, the Alternate Uses task. All experiments contained a contrast between a creative task and a matched non-creative or less-creative task that controlled for the sensorimotor demands of task performance. The activation profiles of the two meta-analyses were non-overlapping, but both pointed to a domain-specific interpretation in which creative production is, at least in part, an enhancement of sensorimotor brain areas involved in non-creative production. The most concordant areas of activation in the motoric meta-analysis were high-level motor areas such as the pre-supplementary motor area and inferior frontal gyrus that interface motor planning and executive control, suggesting a means of uniting domain-specificity and -generality in creative production.
As the blood–brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal ...administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP’s transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.
•Ti oxide having high reducibility was added to La oxide-promoted Pd/SiO2 as a second promoter.•La oxide migration during oxidation was effectively suppressed by the added Ti oxide.•Ti oxide further ...modifies Pd electronically, even for low-temperature reduction, due to its high reducibility.•Pd–La–Ti/SiO2 showed high ethylene selectivity even after oxidation and low-temperature reduction.
La oxide is known to be the best promoter among reducible metal oxides for acetylene hydrogenation. However, it requires high-temperature reduction, which is not feasible in commercial processes. To maintain the enhanced catalytic performance by La oxide addition while lowering the reduction temperature for application in commercial process, we added Ti oxide as a second promoter, which has a higher reducibility than La oxide. The Ti oxide is added to the Pd surface, which has been partially covered by La oxide, and maintains the modified geometric and electronic structures of the Pd catalyst induced by the high-temperature-reduced La oxide even after low-temperature reduction, as confirmed by H2 chemisorption and X-ray photoelectron spectroscopy. Surprisingly, Ti oxide further modifies the electronic structure of Pd, even for low-temperature reduction, due to its high reducibility, leading to higher ethylene selectivity than when La oxide is used exclusively. We also confirmed that a similar additive effect also applies to other metal oxides, i.e., Nb2O5.
Compared to the existing noninvasive methods, temporal interference (TI) current stimulation is an emerging noninvasive neuromodulation technique that can improve the ability to focus an electrical ...field on a target nerve. Induced TI field distribution depends on the anatomical structure of individual neurons, and thus the electrode and current optimization to enhance the field focus must reflect these factors. The current study presents a TI field optimization framework for focusing the stimulation energy on the target tibial nerve through extensive electrical simulations, factoring in individual anatomical differences. We conducted large-scale in-silico experiments using realistic models based on magnetic resonance images of human subjects to evaluate the effectiveness of the proposed methods for tibial nerve stimulation considering overactive bladder (OAB) treatment. The electrode position and current intensity were optimized for each subject using an automated algorithm, and the field-focusing performance was evaluated based on the maximum intensity of the electric fields induced at the target nerve compared with the electric fields in the neighboring tissues. Using the proposed optimization framework, the focusing ability increased by 12% when optimizing the electrode position. When optimizing both the electrode position and current, this capability increased by 11% relative to electrode position optimization alone. These results suggest the significance of optimizing the electrode position and current intensity for focusing TI fields at the target nerve. Our electrical simulation-based TI optimization framework can be extended to enable personalized peripheral nerve stimulation therapy to modulate peripheral nerves.
Herein, non‐polymeric thin cross‐sectional wires were fabricated by injecting materials into elastomeric hollow fibers with subsequent drawing. Once materials were injected into hollow elastic ...fibers, cores were drawn as fibers elongated. Solidifying the core and removing polymeric shell could form free‐standing wires with thin cross‐sections. In this work, two different thin wires, metallic wires (gallium), and SiCN ceramic wires, were fabricated. Although mechanical and physical properties of these wires completely differed, fabrication approaches were identical by drawing materials near room temperature. Solidified wires enhanced mechanical properties of fibers. Thus, fibers could store elastic energy and preserve deformed complex shapes with the assist of solidified cores. Although the wires with thin cross sections are inherently brittle, the relatively low melting point of gallium (29.8°C) allows it to heal easily upon body heating.
Non‐polymeric thin cross‐sectional wires were fabricated by injecting materials into elastomeric hollow fibers with subsequent drawing near room temperature. Once materials were injected into hollow elastic fibers, cores were drawn as fibers elongated. Solidifying the core and removing polymeric shell could form free‐standing wires with thin cross‐sections.
Abstract
Background
Only limited data are available regarding postural stability between anterior cruciate ligament (ACL)-injured patients with medial meniscus (MM) tear and those with lateral ...meniscus (LM) tear. The purpose of this study was to compare preoperative postural stability for both involved and uninvolved knees in ACL rupture combined with MM and LM tears. It was hypothesized that there would be a significant difference in postural stability between these two groups.
Methods
Ninety-three ACL-injured patients (53 combined with MM tears vs. 40 combined with LM tears) were included. Static and dynamic postural stability were evaluated with the overall stability index (OSI), anterior–posterior stability index (APSI), and medial–lateral stability index (MLSI) using stabilometry. Knee muscle strength was evaluated using an isokinetic testing device.
Results
In the static postural stability test, none of the stability indices showed significant differences between the two groups for both knees (
p
> 0.05). In the dynamic postural stability test for involved side knees, the OSI and APSI were significantly higher in the LM tear group compared to the MM tear group (OSI: 2.0 ± 0.8 vs. 1.6 ± 0.5,
p
= 0.001; APSI: 1.5 ± 0.6 vs. 1.3 ± 0.5,
p
= 0.023), but not the MLSI (
p
> 0.05). In the static and dynamic postural stability tests in each group, there were no significant differences between the involved and uninvolved side knees (
p
> 0.05). There was no significant difference in the knee muscle strength between the two groups (
p
> 0.05). All postural stability showed no significant correlation with knee muscle strength (
p
> 0.05).
Conclusion
Dynamic postural stability was poorer in patients with ACL rupture combined with LM tear than in those with MM tear. Therefore, close monitoring for postural stability would be necessary during preoperative and postoperative rehabilitation, especially for patients with ACL rupture combined with LM tear.
Level of evidence: Level III
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•The first G-quadruplex-based aptamer specific for NS1.•Fluorescent aptasensor to diagnose dengue fever.•5’FAM-aptamer detected the fluorescence quenching by NS1-induced structural ...change.•Established aptasensor was rapid and simple to use in a one-shot manner.•High specificity to NS1 over other proteins including those from yellow fever virus.
In this study, we proposed a new G-quadruplex (GQ)-based fluorescent aptasensor using one-shot detection of NS1 for dengue fever diagnosis. To design the aptasensor, Dengue virus-derived NS1-binding aptamer (DBA) that forms a GQ structure was developed. The DBA underwent structural destruction induced by nonstructural protein 1 (NS1), then we aimed to utilize it for optical sensing. Fluorescent detection of the NS1-dependent structural change was performed by applying a fluorescent dye; 6-carboxyfluorescein (FAM) was attached to the 5' end of DBA (5' FAM-DBA). The 5' FAM-DBA could quantitatively detect the fluorescence quenching caused by guanines upon NS1 binding, which was feasible for dengue fever diagnosis. We analyzed to understand the structural and fluorescent characteristics that are involved in the interaction between NS1 and DBA. The results suggested that the central G-tracts were rearranged to adjacent toward the FAM, and that the structure of 5' FAM-DBA bound to NS1 was expected to form base-pairing. Finally, the aptasensor with 5’ FAM-DBA was established after optimization, which contributed to the effective and rapid detection. The aptasensor achieved low detection limits of 2.51 nM in buffer and 8.13 nM in serum. Additionally, it was verified the high specificity using other proteins including yellow fever proteins, and it has the potential to overcome the cross-reactivity with other flaviviruses. Also, the stability of the DF aptasensor was confirmed to give practical usability. Here, we developed a novel GQ-based fluorescent aptasensor for rapid and simple dengue fever diagnosis, which could provide the possibility for use in practical applications.
Here, we proposed an enzyme-linked oligonucleotide assay (ELONA) for yellow fever (YF) diagnosis that uses a pair of aptamers, YFns1-4 and YFns1-31. The aptamers were selected to specifically bind to ...nonstructural protein 1 (NS1), which is secreted at a high concentration after YF infection. We applied the aptamers which did not interfere with each other on binding to the NS1 in a sandwich ELONA. In the assay, the best detection sensitivity was obtained when the combination of YFns1-31 as a capture aptamer and YFns1-4 as a detect aptamer was used. The sensitivity could be attributed to the results of the direct ELONA with each YFns1-4 and YFns1-31; a great absorbance intensity and a broad detectable range of NS1, respectively. The sandwich ELONA achieved a low detection limit of 0.85 nM in buffer and was highly specific to the YFV-NS1 as its detection signals were significantly distinct from those of other flavivirus-derived NS1. In addition, the assay showed a desirable sensitivity in serum-spiked condition. Our developed sandwich ELONA can be a new practical and applicable serological diagnostics in YF endemic regions where other flaviviruses coexist and facilities for complex diagnostic tests are lacking.
We developed a pair of aptamers and applied them to enzyme-linked oligonucleotide assay (ELONA) for yellow fever virus (YFV) diagnosis, achieving highly selective and sensitive detection of nonstructural protein 1 (NS1). Display omitted
•Two different YFV-NS1 specific aptamers have been developed.•Direct ELONA using each aptamer was conducted to test the sensitivity of the aptamers.•Sandwich ELONA using the aptamers was first proposed for the diagnosis of yellow fever.•The proposed sandwich ELONA provided the possibility for serological test in YF endemic regions.
Tuberculosis (TB) is one of the leading cause of infection-related deaths worldwide. Conventional diagnostic methods for TB require infectious samples and are time-consuming. In this study, we aimed ...to develop an aptamer-based qPCR (Apta-qPCR) assay to diagnose TB safely and rapidly. The assay uses a single-stranded DNA aptamer with affinity for a TB biomarker, ESAT6, and molecular beacon capable of hybridizing to the aptamer. Apta-qPCR enables aptamer-mediated detection of ESAT6 via qPCR, wherein the aptamer serves as both a target recognition agent and template for quantification. This diagnostic method achieved a desirable detection limit of 2.03 nM in buffer and 2.56 nM in serum-spiked conditions with high reproducibility and reliability. In addition, the diagnostic performance was verified in a clinical application using human serum samples from normal controls and patients with active TB. The assay showed 50.0% sensitivity, 91.7% specificity, and 78.1% accuracy, similar to sputum smear microscopy, which is currently the most used method for TB diagnosis. Importantly, this assay has an advantage over smear microscopy in that it reduces the risk of infection by avoiding the use of sputum-containing infectious pathogens.
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•An aptmer-based qPCR (Apta-qPCR) assay was developed to diagnose tuberculosis.•Apta-qPCR can safely detect a protein biomarker ESAT6 from non-infectious serum samples.•The assay shows high clinical sensitivity, specificity and accuracy.•Apta-qPCR can be used to detect various protein biomarkers.
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