Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 33
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Nature ; 631(8019): 106-110, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38839961

ABSTRACT

Understanding the factors governing the stability of fault slip is a crucial problem in fault mechanics1-3. The importance of fault geometry and roughness on fault-slip behaviour has been highlighted in recent lab experiments4-7 and numerical models8-11, and emerging evidence suggests that large-scale complexities in fault networks have a vital role in the fault-rupture process12-18. Here we present a new perspective on fault creep by investigating the link between fault-network geometry and surface creep rates in California, USA. Our analysis reveals that fault groups exhibiting creeping behaviour show smaller misalignment in their fault-network geometry. The observation indicates that the surface fault traces of creeping regions tend to be simple, whereas locked regions tend to be more complex. We propose that the presence of complex fault-network geometries results in geometric locking that promotes stick-slip behaviour characterized by earthquakes, whereas simpler geometries facilitate smooth fault creep. Our findings challenge traditional hypotheses on the physical origins of fault creep explained primarily in terms of fault friction19-21 and demonstrate the potential for a new framework in which large-scale earthquake frictional behaviour is determined by a combination of geometric factors and rheological yielding properties.

3.
Sensors (Basel) ; 22(2)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35062556

ABSTRACT

Surface-Enhanced Raman Spectroscopy (SERS) is often used for heavy metal ion detection. However, large variations in signal strength, spectral profile, and nonlinearity of measurements often cause problems that produce varying results. It raises concerns about the reproducibility of the results. Consequently, the manual classification of the SERS spectrum requires carefully controlled experimentation that further hinders the large-scale adaptation. Recent advances in machine learning offer decent opportunities to address these issues. However, well-documented procedures for model development and evaluation, as well as benchmark datasets, are missing. Towards this end, we provide the SERS spectral benchmark dataset of lead(II) nitride (Pb(NO3)2) for a heavy metal ion detection task and evaluate the classification performance of several machine learning models. We also perform a comparative study to find the best combination between the preprocessing methods and the machine learning models. The proposed model can successfully identify the Pb(NO3)2 molecule from SERS measurements of independent test experiments. In particular, the proposed model shows an 84.6% balanced accuracy for the cross-batch testing task.


Subject(s)
Metal Nanoparticles , Metals, Heavy , Machine Learning , Reproducibility of Results , Spectrum Analysis, Raman
4.
Molecules ; 27(19)2022 Oct 02.
Article in English | MEDLINE | ID: mdl-36235052

ABSTRACT

Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligands have been mostly limited to either CRBN or VHL ligands. Those PROTACs showed their limitation due to the cell type specific expression of E3 ligases and recently reported resistance toward PROTACs with CRBN ligands or VHL ligands. To overcome these hurdles, the discovery of various E3 ligase ligands has been spotlighted to improve the current PROTAC technology. This review focuses on currently reported E3 ligase ligands and their application in the development of PROTACs.


Subject(s)
Ubiquitin-Protein Ligases , Ubiquitin , Ligands , Proteins/metabolism , Proteolysis , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism
5.
J Phys Ther Sci ; 30(2): 234-237, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29545684

ABSTRACT

[Purpose] The purpose of this study is to study the impact of knee extensor strength, which is an index of the degree of physical activity on lung capacity in older women. [Subjects and Methods] Thirty-three older women who participated in the exercise program hosted by a senior citizen center and S University located in Busan. Force vital capacity (FVC) was measured with digital spirometry (Pony FX, COSMED Inc., Italy). Three rounds of measurements were taken for each participant, with one-minute rests between the tests. The means were computed for analysis. Knee extensor strength was measured with a hand-held dynamometer (HHD, MicroFET2®, Hogan Health Industries, Inc., UT, USA). Three rounds of measurements were taken for each knee extensor muscle, after which the mean of the measurements was taken for each side. The higher knee extensor muscle strength value was used for the analysis. [Results] Knee extensor muscle strength had significant positive correlations with Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), Peak expiratory flow (PEF), and Forced expiratory flow (FEF 25-75%). Association between knee extensor muscle strength and pulmonary function suggested that weakening of the elderly's knee extensor muscle strength has an adverse effect on pulmonary function, although the explanatory power was weak. [Conclusion] Knee extensor muscle weakness in elderly females restricts their physical activity and mobility, thereby serving as a key factor in decreasing their lung capacity.

6.
Sensors (Basel) ; 17(1)2017 Jan 07.
Article in English | MEDLINE | ID: mdl-28067856

ABSTRACT

Due to the necessity of the low-power implementation of newly-developed electrocardiogram (ECG) sensors, exact ECG data reconstruction from the compressed measurements has received much attention in recent years. Our interest lies in improving the compression ratio (CR), as well as the ECG reconstruction performance of the sparse signal recovery. To this end, we propose a sparse signal reconstruction method by pruning-based tree search, which attempts to choose the globally-optimal solution by minimizing the cost function. In order to achieve low complexity for the real-time implementation, we employ a novel pruning strategy to avoid exhaustive tree search. Through the restricted isometry property (RIP)-based analysis, we show that the exact recovery condition of our approach is more relaxed than any of the existing methods. Through the simulations, we demonstrate that the proposed approach outperforms the existing sparse recovery methods for ECG reconstruction.


Subject(s)
Electrocardiography , Algorithms , Data Compression , Pressure
7.
J Phys Ther Sci ; 29(4): 658-661, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28533605

ABSTRACT

[Purpose] Although lung capacity in the elderly is affected by age, little research has been performed studying decreasing lung capacity in relation to increasing life expectancy. The aim of this study was to examine the effects of increased life span on the lung capacity of women. [Subjects and Methods] The subjects of this study were 55 healthy elderly women over 60 years of age who were living in Busan. Subjects were classified in the following age categories: 60s, 70s and 80s. For the pulmonary function test, a spirometry (Pony FX, COSMED Inc., Italy) was used. The item for measurement of pulmonary function in elderly women was maximum-effort expiratory spirogram (MES). The pulmonary function test was performed 3 times, and its mean value was used for analysis. [Results] Among items of maximum-effort expiratory spirogram, a significant difference according to age was demonstrated in forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow, maximum expiratory flow 75%, maximum expiratory flow 50%, and inspiratory capacity. [Conclusion] According to this study, lung capacity decreases remarkably as age increases. In conclusion, a continuous exercise program beginning at an early age is essential to prevent decrease in lung capacity as age progresses.

8.
J Phys Ther Sci ; 29(4): 707-712, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28533614

ABSTRACT

[Purpose] The purpose of this research is to investigate the effect of the method of bridge exercise on the change of rectus abdominis muscle and the muscle activity of paraspinal muscles while doing treadmill walking with high heels. [Subjects and Methods] The subjects of this research are healthy female students consisting of 10 persons performing bridge exercises in a supine group, 10 persons performing bridge exercises in a prone group, and 10 persons in a control group while in S university in Busan. Bridge exercise in supine position is performed in hook lying position. Bridge exercise in prone position is plank exercise in prostrate position. To measure the strength of rectus abdominis muscle, maintaining times of the posture was used. To measure the muscle activity of paraspinal muscles, EMG (4D-MT & EMD-11, Relive, Korea) was used. [Results] The strength of rectus abdominis muscle of both bridge exercises in the supine group and bridge exercises in the prone group increases significantly after exercise. The muscle activity of paraspinal muscle such as thoracic parts and lumbar parts in bridge exercises in the prone group decreases statistically while walking on a treadmill with high heels. Muscle activity of thoracic parts paraspinal muscle and bridge exercises in the supine group decreased significantly. [Conclusion] According to this study, we noticed that bridge exercise in a prone position is desirable for women who prefer wearing high heels as a back pain prevention exercise method.

9.
Tumour Biol ; 37(6): 7315-25, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26671552

ABSTRACT

Here, we report a new intracellular signaling pathway involved in γ-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion and migration of A549 cells (a non-small cell lung cancer (NSCLC) cell line). Our results revealed that IR increased the invasion/migration of A549 cells, and this effect was decreased by 10 nM PA treatment. PA also inhibited the expressions/activities of matrix metalloprotase (MMP) -2, MMP-9, and vimentin, suggesting that PA could block the IR-induced epithelial-mesenchymal transition (EMT). The IR-induced increases in invasion/migration were associated with the activation of EGFR-AKT, and PA inhibited this effect. P38 and p44/42 ERK were also involved in IR-induced invasion/migration, and combined treatments with PA plus inhibitors of each MAPK synergistically blocked this invasion/migration. In terms of transcription factors (TFs), IR-induced increases in cyclic AMP response element-binding protein-1 (CREB-1) and signal transducer and activator of transcription 3 (STAT3) increased invasion/migration and EMT. PA also inhibited these transcription factors and then blocked IR-induced invasion/migration. Collectively, these results indicate that IR induces cancer cell invasion/migration by activating the EGFR-p38/ERK-CREB-1/STAT3-EMT pathway and that PA blocks this pathway to inhibit IR-induced invasion/migration.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Epithelial-Mesenchymal Transition/radiation effects , Gamma Rays , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Lung Neoplasms/pathology , Neoplasm Proteins/antagonists & inhibitors , Podophyllotoxin/analogs & derivatives , Signal Transduction/radiation effects , Carcinoma, Non-Small-Cell Lung/enzymology , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/radiation effects , Drug Screening Assays, Antitumor , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Intracellular Signaling Peptides and Proteins/physiology , Lung Neoplasms/enzymology , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/physiology , Podophyllotoxin/pharmacology , Signal Transduction/drug effects , Transcription Factors/antagonists & inhibitors , Transcription Factors/physiology
10.
Sensors (Basel) ; 16(6)2016 Jun 16.
Article in English | MEDLINE | ID: mdl-27322267

ABSTRACT

Electroencephalograms (EEGs) measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI) studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR) is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP) signal that represents a brain's response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE) schemes based on a joint maximum likelihood (ML) criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°.


Subject(s)
Electroencephalography/methods , Likelihood Functions , Brain/physiology , Brain-Computer Interfaces , Evoked Potentials/physiology , Humans , Models, Theoretical , Signal Processing, Computer-Assisted
11.
Am J Physiol Regul Integr Comp Physiol ; 309(5): R459-66, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26084693

ABSTRACT

While acute treatment with beetroot juice (BRJ) containing nitrate (NO3 (-)) can lower systolic blood pressure (SBP), afterload, and myocardial O2 demand during submaximal exercise, effects of chronic supplementation with BRJ (containing a relatively low dose of NO3 (-), 400 mg) on cardiac output (CO), SBP, total peripheral resistance (TPR), and the work of the heart in response to dynamic exercise are not known. Thus, in 14 healthy males (22 ± 1 yr), we compared effects of 15 days of both BRJ and nitrate-depleted beetroot juice (NDBRJ) supplementation on plasma concentrations of NOx (NO3 (-)/NO2 (-)), SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), CO, TPR, and rate pressure product (RPP) at rest and during progressive cycling exercise. Endothelial function was also assessed via flow-mediated dilation (FMD). BRJ supplementation increased plasma NOx from 83.8 ± 13.8 to 167.6 ± 13.2 µM. Compared with NDBRJ, BRJ reduced SBP, DBP, MAP, and TPR at rest and during exercise (P < 0.05). In addition, RPP was decreased during exercise, while CO was increased, but only at rest and the 30% workload (P < 0.05). BRJ enhanced FMD-induced increases in brachial artery diameter (pre: 12.3 ± 1.6%; post: 17.8 ± 1.9%). We conclude that 1) chronic supplementation with BRJ lowers blood pressure and vascular resistance at rest and during exercise and attenuates RPP during exercise and 2) these effects may be due, in part, to enhanced endothelium-induced vasodilation in contracting skeletal muscle. Findings suggest that BRJ can act as a dietary nutraceutical capable of enhancing O2 delivery and reducing work of the heart, such that exercise can be performed at a given workload for a longer period of time before the onset of fatigue.


Subject(s)
Beta vulgaris , Diet , Dietary Supplements , Endothelium, Vascular/physiology , Exercise , Fruit and Vegetable Juices , Hemodynamics , Muscle, Skeletal/blood supply , Nitrates/administration & dosage , Arterial Pressure , Bicycling , Cross-Over Studies , Double-Blind Method , Heart Rate , Humans , Male , Muscle Contraction , Muscle Fatigue , Plant Roots , Time Factors , Vascular Resistance , Young Adult
12.
J Phys Ther Sci ; 27(1): 11-3, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25642026

ABSTRACT

[Purpose] This study was performed to examine the immediate effects of spinal mobilization with arm movements (SMWAMs) for strengthening the shoulder muscles. [Subjects] The subjects of this study were 12 healthy male students who were studying at S University, Busan City. They had no musculoskeletal disease, or upper congenital malformation, and had no history of surgery or neurological disease. [Methods] The SMWAMs were performed on the 4th cervical vertebra (C4). For stimulation of the 5th cervical nerve, the spinous process of the C4 was pushed to the left and held in place. Then the arm was abducted to the point where spinous process was felt, and the range of abduction was examined. Subsequently, the abduction movement was repeated 10 times to the same point, and the gliding of C4 was held until the arm returned to the starting position. During the treatment, the head and the trunk were held in the correct posture. [Results] After SMWAMs had been performed, the muscular strength of shoulder flexion, extension and adduction significantly increased. [Conclusion] In our opinion, the SMWAMs are a very useful method for correcting spinal malalignment, and for stimulating the joint mechanoreceptors without the risks of manipulation. SMWAM is a valuable therapy method that can complement the demerits of mobilization.

13.
J Phys Ther Sci ; 27(9): 2793-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26504295

ABSTRACT

[Purpose] The purpose of this study is to examine the effects of Juchumseogi and Juchumseo Jireugi motions on muscle activation of the paraspinal muscles. [Subjects] The subjects of this study were 20 healthy male students who listened to an explanation of the study methods and the purpose of the experiment, and agreed to participate in the study. [Methods] Muscle activation measurements of the paraspinal muscles at C3, T7, and L3 were taken while standing still and while performing Juchumseogi and Juchumseo Jireugi movements. The Juchumseogi and Juchumseo Jireugi motions were performed 3 times, and its mean value was used for analysis. [Results] The right and left muscle activation of paraspinal muscles induced by Juchumseogi and Juchumseo Jireugi motions in C3 and T7 were significantly higher than those induced by just standing. Muscle activation of paraspinal muscles induced by Juchumseo Jireugi motions in C3, T7, and L3 were significantly higher than those induced by Juchumseogi alone. The right and left muscle activation of paraspinal muscles induced by Juchumseo Jireugi motion in C3, T7, and L3 were significantly higher than those induced by standing and Juchumseogi alone. [Conclusion] This study demonstrated that Juchumseogi and Juchumseo Jireugi motions of Taekwondo could increase muscle activation of paraspinal muscles, and Juchumseo Jireugi motions were more effective for enhancing muscle activation of paraspinal muscles.

14.
J Gambl Stud ; 30(2): 403-22, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23334577

ABSTRACT

This study revised the theory of planned behavior (TPB) by incorporating the new concepts of gambling passion and responsible gambling strategy (RGS) to predict gamblers' intention to gamble in online sports betting. The data were collected at the end of March in 2012 through an online gambling website. The findings indicated that the inclusion of two types of gambling passion and two types of RGS explains online gambling intention well. Specifically, out of the original antecedent predictors of TPB, attitude toward online gambling was positively related to harmonious passion. Subjective norm had a positive relationship with both harmonious and obsessive passion. The results also showed that perceived behavioral control does not have a significant effect on the two gambling passions but has a direct and significant influence on behavioral intention. Additionally, the compulsory RGS had a negative effect on obsessive passion, whereas supplementary RGS had concurrent positive impacts on harmonious and obsessive passion. Lastly, the two gambling passions were notable predictors of behavioral intention toward online sports betting.


Subject(s)
Decision Making , Gambling/psychology , Intention , Internet/statistics & numerical data , Adult , Attitude , Female , Humans , Male , Middle Aged , Psychological Theory , Young Adult
15.
J Phys Ther Sci ; 26(7): 1079-82, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25140101

ABSTRACT

[Purpose] This research investigated the relationship between elbow joint angle and elbow flexor and extensor strength and activation, taking into consideration the length-tension tension curve of the muscle. [Subjects] There were 30 research subjects in total, 15 male and 15 female college students from Busan S University who had no functional disabilities that might affect measurement of muscle strength and muscle activation, and none had they experienced any damage in their upper extremities or hands. [Methods] The elbow joint angles were positioned at angles of 56°, 70° and 84°, and then muscle strength and activation were compared. Repeated measures ANOVA was used for statistical analysis, and the paired t-test was used to identify the difference between each angle. We used the SPSS for windows (ver. 21.0) statistical software and a significance level of α=0.05. [Results] The results showed that muscle strength and activation of the biceps was highest when the joint was placed at 56°. On the other hand, for the triceps, the result was highest when the joint angle was placed at 84°. [Conclusion] The tests confirmed that muscle strength and activation were highest at the joint angle at which the muscle was stretched to 20% more than the resting position in concentric contraction.

16.
Indian J Med Res ; 138(6): 922-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24521637

ABSTRACT

BACKGROUND & OBJECTIVES: Atopic diseases, including atopic dermatitis (AD), allergy and asthma, are complex diseases resulting from the effect of multiple genetic and interacting environmental factors on their pathophysiology. The genetic basis is incompletely understood; however, recent studies have shown an association between loss-of-function variants of the filaggrin gene (FLG) and atopic dermatitis. The aim of this study was to determine whether FLG variants can serve as a predictor for atopic diseases in Korean individuals. METHODS: A total of 648 subjects were genotyped for the FLG P478S (rs11584340, C/T base change) polymorphism (322 patients and 326 controls). Serum levels of free fatty acids (FFA) and IgE were later stratified to determine the effects of the FLG polymorphism on AD. RESULTS: A significant difference in genotype frequency was found between AD patients and controls in the FLG P478S polymorphism. The FLG P478S T allele carrier (TT+TC) was associated with AD risk (odds ratio = 1.877, 95% confidence interval 1.089 to 3.234). In addition, the P478S T allele was related to high levels of FFA in AD patients (471.79 ± 298.96 vs. 333.54 ± 175.82 µg eq/l, P <0.05). INTERPRETATION & CONCLUSIONS: The results of the present study suggest that the FLG P478S polymorphism alone and combined with other factors influences FFA levels and increases the susceptibility to AD.


Subject(s)
Asthma/genetics , Dermatitis, Atopic/genetics , Intermediate Filament Proteins/genetics , Rhinitis, Allergic/genetics , Adult , Asthma/pathology , Child, Preschool , Dermatitis, Atopic/pathology , Female , Filaggrin Proteins , Genetic Association Studies , Genetic Predisposition to Disease , Heterozygote , Humans , Intermediate Filament Proteins/blood , Korea , Male , Middle Aged , Polymorphism, Single Nucleotide , Rhinitis, Allergic/pathology
17.
J Phys Ther Sci ; 25(10): 1335-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24259788

ABSTRACT

[Purpose] The purpose of this study was to determine the effects of abdominal hollowing during lower-limb proprioceptive neuromuscular facilitation (PNF) training on the activation of contralateral muscles. [Subjects] Twenty male college students without symptoms or signs of muscular or nervous disease participated in this experiment after signing a consent form. [Methods] All the subjects were measured with electromyography (EMG) in a muscle activation test before and after abdominal hollowing. In the PNF program, the lower-limb pattern of PNF training, was maintained for 5 seconds, followed by a 2-minute break. This was repeated three times. The resting time between sets was 30 minutes. Surface EMG (Keypoint, Medtronic Inc., USA) was used for the measurements, and the highest value of three measurements was used in the analysis. [Result] The results revealed a significant change in the muscular activation of the opposite-side lower limbs. The muscular activations of the vastus lateralis, tibialis anterior, semitendinosus and gastrocnemius were increased significantly after the abdominal hollowing. [Conclusion] The findings suggest that abdominal hollowing in PNF pattern training can be effective at promoting muscular activation of the contralateral muscles. To promote muscular activation of the opposite side in lower-limb PNF pattern training, abdominal hollowing should be considered to improve the effect of PNF pattern training.

18.
Biodivers Data J ; 11: e110313, 2023.
Article in English | MEDLINE | ID: mdl-37840603

ABSTRACT

Background: The genus Proutia Tutt, 1899 (Lepidoptera, Psychidae) comprises 14 species found throughout the world. In East Asia, three species, Proutiachinensis Hättenschwiler & Chao, 1990, P.maculatella Saigusa & Sugimoto, 2014 and P.nigra Saigusa & Sugimoto, 2014, are known from Korea, Japan and China. New information: Proutiacornucervae Roh & Lee, sp. nov. is newly recognised from Korea. In addition, Bruandellaniphonica (Hori) is transferred to genus Proutia. Male and genitalia of the species are described and DNA barcodes are provided.

19.
Biosensors (Basel) ; 12(10)2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36290975

ABSTRACT

Polydimethylsiloxane (PDMS) is a widely used material in laboratories for fabricating microfluidic devices with a rapid and reproducible prototypingability, owing to its inherent properties (e.g., flexibility, air permeability, and transparency). However, the PDMS channel is easily deformed under pressures applied to generate flows because of its elasticity, which can affect the robustness of experiments. In addition, air permeability of PDMS causes the pervaporation of water, and its porous structure absorbs oil and even small hydrophobic molecules, rendering it inappropriate for chemically demanding or day-long experiments. In this study, we develop a rapid and reproducible fabrication method for polymer-based rigid microfluidic devices, using epoxy resin that can overcome the limitations of PDMS channels, which are structurally and chemically robust. We first optimize a high-resolution fabrication protocol to achieve convenient and repeatable prototyping of polymeric devices via epoxy casting using PDMS soft molds. In addition, we compare the velocity changes in PDMS microchannels by tracking fluorescent particles in various flows (~133 µL/min) to demonstrate the structural robustness of the polymeric device. Furthermore, by comparing the adsorption of fluorescent hydrophobic chemicals and the pervaporation through channel walls, we demonstrate the excellent chemical resistance of the polymeric device and its suitability for day-long experiments. The rigid polymeric device can facilitate lab-on-chip research and enable various applications, such as high-performance liquid chromatography, anaerobic bacterial culture, and polymerase chain reaction, which require chemically or physically demanding experiments.


Subject(s)
Epoxy Resins , Lab-On-A-Chip Devices , Dimethylpolysiloxanes/chemistry , Polymers , Water
20.
Exp Mol Med ; 54(12): 2200-2209, 2022 12.
Article in English | MEDLINE | ID: mdl-36509830

ABSTRACT

Neuroinflammation is one of the critical processes implicated in central nervous system (CNS) diseases. Therefore, alleviating neuroinflammation has been highlighted as a therapeutic strategy for treating CNS disorders. However, the complexity of neuroinflammatory processes and poor drug transport to the brain are considerable hurdles to the efficient control of neuroinflammation using small-molecule therapeutics. Thus, there is a significant demand for new chemical entities (NCEs) targeting neuroinflammation. Herein, we rediscovered benzopyran-embedded tubulin inhibitor 1 as an anti-neuroinflammatory agent via phenotype-based screening. A competitive photoaffinity labeling study revealed that compound 1 binds to tubulin at the colchicine-binding site. Structure-activity relationship analysis of 1's analogs identified SB26019 as a lead compound with enhanced anti-neuroinflammatory efficacy. Mechanistic studies revealed that upregulation of the tubulin monomer was critical for the anti-neuroinflammatory activity of SB26019. We serendipitously found that the tubulin monomer recruits p65, inhibiting its translocation from the cytosol to the nucleus and blocking NF-κB-mediated inflammatory pathways. Further in vivo validation using a neuroinflammation mouse model demonstrated that SB26019 suppressed microglial activation by downregulating lba-1 and proinflammatory cytokines. Intraperitoneal administration of SB26019 showed its therapeutic potential as an NCE for successful anti-neuroinflammatory regulation. Along with the recent growing demands on tubulin modulators for treating various inflammatory diseases, our results suggest that colchicine-binding site-specific modulation of tubulins can be a potential strategy for preventing neuroinflammation and treating CNS diseases.


Subject(s)
Tubulin Modulators , Tubulin , Mice , Animals , Tubulin Modulators/metabolism , Tubulin/metabolism , Neuroinflammatory Diseases , NF-kappa B/metabolism , Microtubules/metabolism , Colchicine/pharmacology , Colchicine/therapeutic use , Colchicine/metabolism , Microglia/metabolism , Lipopolysaccharides/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL