ABSTRACT
Electrochemical sensing techniques for small molecules have progressed in many applications, including disease diagnosis and prevention as well as monitoring of health conditions. However, affinity-based detection for low-abundance small molecules is still challenging due to the imbalance in target-to-receptor size ratio as well as the lack of a highly sensitive signal transducing method. Herein, we introduced nanoscale electrochemistry in affinity-based small molecule detection by measuring the change of quantum electrochemical properties with a nanoscale artificial receptor upon binding. We prepared a nanoscale molecularly imprinted composite polymer (MICP) for cortisol by electrochemically copolymerizing ß-cyclodextrin and redox-active methylene blue to offer a high target-to-receptor size ratio, thus realizing "bind-and-read" detection of cortisol as a representative target small molecule, along with extremely high sensitivity. Using the quantum conductance measurement, the present MICP-based sensor can detect cortisol from 1.00 × 10-12 to 1.00 × 10-6 M with a detection limit of 3.93 × 10-13 M (S/N = 3), which is much lower than those obtained with other electrochemical methods. Moreover, the present MICP-based cortisol sensor exhibited reversible cortisol sensing capability through a simple electrochemical regeneration process without cumbersome steps of washing and solution change, which enables "continuous detection". In situ detection of cortisol in human saliva following circadian rhythm was carried out with the present MICP-based cortisol sensor, and the results were validated with the LC-MS/MS method. Consequently, this present cortisol sensor based on nanoscale MICP and quantum electrochemistry overcomes the limitations of affinity-based biosensors, opening up new possibilities for sensor applications in point-of-care and wearable healthcare devices.
Subject(s)
Biosensing Techniques , Molecular Imprinting , Humans , Electrochemistry , Hydrocortisone , Chromatography, Liquid , Tandem Mass Spectrometry , Biosensing Techniques/methods , Electrochemical Techniques/methods , Limit of Detection , ElectrodesABSTRACT
Melatonin, a hormone secreted by the pineal gland of vertebrates, regulates sleep, blood pressure, and circadian and seasonal rhythms, and acts as an antioxidant and anti-inflammatory agent. We investigated the protective effects of melatonin against markers of D-galactose (D-Gal)-induced hepatocellular aging, including liver inflammation, hepatocyte structural damage, and non-alcoholic fatty liver. Mice were divided into four groups: phosphate-buffered saline (PBS, control), D-Gal (200 mg/kg/day), melatonin (20 mg/kg), and D-Gal (200 mg/kg) and melatonin (20 mg) cotreatment. The treatments were administered once daily for eight consecutive weeks. Melatonin treatment alleviated D-Gal-induced hepatocyte impairment. The AST level was significantly increased in the D-Gal-treated groups compared to that in the control group, while the ALT level was decreased compared to the melatonin and D-Gal cotreated group. Inflammatory genes, such as IL1-ß, NF-κB, IL-6, TNFα, and iNOS, were significantly increased in the D-Gal aging model, whereas the expression levels of these genes were low in the D-Gal and melatonin cotreated group. Interestingly, the expression levels of hepatic steatosis-related genes, such as LXRα, C/EBPα, PPARα, ACC, ACOX1, and CPT-1, were markedly decreased in the D-Gal and melatonin cotreated group. These results suggest that melatonin suppresses hepatic steatosis and inflammation in a mouse model of D-Gal-induced aging.
ABSTRACT
Brassica oleracea var. italica (broccoli), a member of the cabbage family, is abundant with many nutrients, including vitamins, potassium, fiber, minerals, and phytochemicals. Consequently, it has been used as a functional food additive to reduce oxidative stress and inflammatory responses. In the current study, the effects of sulforaphane-rich broccoli sprout extract (BSE) on the inflammatory response were investigated in vitro and in vivo. Comparative high-performance liquid chromatography analysis of sulforaphane content from different extracts revealed that 70% ethanolic BSE contained more sulforaphane than the other extracts. qPCR and enzyme immunoassay analyses revealed that BSE markedly reduced the expression of proinflammatory cytokines and mediators, including cyclooxygenase 2, interleukin (IL)-1ß, IL-6, IL-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Pretreatment with BSE improved the survival rate and suppressed alanine aminotransferase and aspartate aminotransferase expression in LPS-induced endotoxemic mice, while proinflammatory cytokines such as IL-1ß, TNF-α, IL-6, cyclooxygenase-2, and iNOS decreased dramatically in the LPS-induced liver injury model via BSE treatment. Additionally, F4/80 immunostaining showed that BSE suppressed hepatic macrophage infiltration in the liver after lipopolysaccharide injection. In conclusion, BSE may be a potential nutraceutical for preventing and regulating excessive immune responses in inflammatory disease.
ABSTRACT
Lacquer sap has been traditionally used in coatings and artwork. Suitable types of lacquer are required to preserve and restore artifacts. Recently, unsuitable cashew nut shell liquid (CNSL) has often been mixed with lacquer sap, so it is necessary to identify the characteristics of lacquer sap by the production area. However, research is still focused on urushiol and laccol. In this study, Myanmarese lacquer sap collected from Gluta usitata, which contains thitsiol as the main component, was analyzed by HPLC to quantify thitsiol using the standards 3-(10-phenyldecyl) benzene-1,2-diol (thitsiol 16) and 3-(8Z,11Z-pentadecadienyl)-benzenediol (urushiol 15:2) as markers, and calibration curves were plotted. The coefficients of determination (R2) for thitsiol 16 and urushiol 15:2 were 0.9985 and 0.9983, respectively. In addition, a blind test was conducted to confirm that accurate quantitative analysis was possible even when Myanmarese lacquer was mixed with lacquer from another production area, which contained urushiol as the main component, and CNSL, which contained cardol, a completely different catechol. Quantitative analysis of thitsiol 16 and urushiol 15:2 in Myanmarese lacquer using HPLC can be used to evaluate the quality of lacquer sap and for more sophisticated activities such as restoration by classifying differences in lacquer sap by the production area.
ABSTRACT
A highly sensitive tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)32+) electrogenerated chemiluminescence (ECL) sensor based on a graphene-titania-Nafion composite film has been prepared in a simple one-step manner. In the present work, a highly concentrated 0.1 M Ru(bpy)32+ solution was mixed with an as-prepared graphene-titania-Nafion composite solution (1:20, v/v), and then a small aliquot (2 µL) of the resulting mixture solution was cast on a glassy carbon electrode surface. This one-step process for the construction of an ECL sensor shortens the fabrication time and leads to reproducible ECL signals. Due to the synergistic effect of conductive graphene and mesoporous sol-gel derived titania-Nafion composite, the present ECL sensor leads to a highly sensitive detection of tripropylamine from 1.0 × 10-8 M to 2.0 × 10-3 M with a detection limit of 0.8 nM (S/N = 3), which is lower in comparison to that of the ECL sensor based on the corresponding ECL sensor based on the titania-Nafion composite containing carbon nanotube. The present ECL sensor also shows a good response for nicotinamide adenine dinucleotide hydrogen (NADH) from 1.0 × 10-6 M to 1.0 × 10-3 M with a detection limit of 0.4 µM (S/N = 3). Thus, the present ECL sensor can offer potential benefits in the development of dehydrogenase-based biosensors.
Subject(s)
Graphite , Ruthenium , 2,2'-Dipyridyl , Fluorocarbon Polymers , Luminescence , Luminescent Measurements/methods , Organometallic Compounds , TitaniumABSTRACT
We first observed the spin-to-charge conversion due to both the inverse Rashba-Edelstein effect (IREE) and inverse spin-Hall effect in a holey multilayer molybdenum disulfide (MoS2) intermediate layer in a Pt/YIG structure via LSSE measurements under nonequilibrium magnetization. We found an enhancement of approximately 238%, 307%, and 290% in the longitudinal spin Seebeck effect (LSSE) voltage, spin-to-charge current, and thermoelectric (TE) power factor, respectively, compared with the monolayer MoS2 interlayer in a Pt/YIG structure. Such an enhancement in the LSSE performance of Pt/holey MoS2/YIG can be explained by the improvement of spin accumulation in the Pt layer by induced spin fluctuation as well as increased additional spin-to-charge conversion due to in-plane IREE. Our findings represent a significant achievement in the understanding of spin transport in atomically thin MoS2 interlayers and pave the way toward large-area TE energy-harvesting devices in two-dimensional transition metal dichalcogenide materials.
ABSTRACT
BACKGROUND: Enlarged facial pores can be an early manifestation of skin aging and they are a common aesthetic concern for Asians. However, studies of improving the appearance of enlarged pores have been limited. OBJECTIVE: The authors aimed to study the application of CO2 fractional laser treatment in patients with enlarged facial pores. METHODS: A total of 32 patients with dilated facial pores completed 3 consecutive sessions of low energy level treatments with a fractional CO2 laser at 4-week intervals. Image analysis was performed to calculate the number of enlarged pores before each treatment session and 12 weeks after the final treatment. RESULTS: After application of laser treatments, there was a significant decrease in the number of enlarged pores. The mean number of enlarged pores was decreased by 28.8% after the second session and by 54.5% at post-treatment evaluation. Post-treatment side effects were mild and transitory. Histological and immunohistochemical analyses demonstrated clear increases in the number of collagen fibers and the expression of transforming growth factor-ß1. CONCLUSION: The short-term results showed that treatment with low energy level CO2 fractional laser therapy could be a safe and effective option for patients with Fitzpatrick skin Types III and IV who are concerned with enlarged pores.
Subject(s)
Face/radiation effects , Lasers, Gas/therapeutic use , Low-Level Light Therapy/instrumentation , Skin Aging/radiation effects , Skin/pathology , Skin/radiation effects , Adult , Asian People , Face/pathology , Female , Humans , Male , Middle Aged , Prospective Studies , Skin Aging/pathologyABSTRACT
BACKGROUND: Although various minimal invasive approaches are available for aging skin laxity, they alone may not lead to notably satisfactory results. OBJECTIVE: To evaluate the effectiveness and safety of combination regimen with monopolar radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and tightening. METHODS: Twenty-two Korean participants with aging face received a sequential single session of MRF and IFUS treatment. Objective and subjective assessments for improvement were performed at the 20-week post-treatment. Safety profiles were also recorded, and skin biopsies were taken at baseline and follow-up visit. RESULTS: Based on the objective assessment for the overall facial skin tightening and laxity, 19 patients (90%) demonstrated "moderate" or better improvements (more than 25%) compared with baseline. Specifically, improvements of skin laxity and sagging, and droopy jaw line were more noticeable compared with that of superficial skin texture (P < 0.05). Subjective satisfactions were generally consistent with objective findings, and no serious adverse effect was observed. Histologic evaluation showed increased dermal collagen fibers throughout the dermis after treatments (P < 0.05). CONCLUSION: Combination treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening with satisfactory safety profiles in Asian subjects.
Subject(s)
Cosmetic Techniques , Face , Radiofrequency Therapy , Skin Aging , Ultrasonic Therapy/methods , Adult , Aged , Asian People , Combined Modality Therapy , Female , Humans , Middle Aged , Patient Satisfaction , Radio Waves/adverse effects , Rejuvenation , Republic of Korea , Ultrasonic Therapy/adverse effectsABSTRACT
RATIONALE: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that have a high vapor pressure at room temperature. Some VOCs have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), because they can bind to DNA and cause cell mutations. Therefore, monitoring of VOCs in human urine is very important to evaluate the correlation between exposure to VOCs and human disease. METHODS: We have developed an improved analytical method for the simultaneous determination of VOCs with a wide range of polarities in human urine samples by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography/mass spectrometry (GC/MS). In the improved method, a bi-polar carboxen-polydimethylsiloxane (CAR/PDMS) fiber was used for the optimized extraction of 15 VOCs with a wide range of polarities, including benzene, toluene, ethylbenzene, xylenes (BTEX), alkylbenzenes, cresols, and naphthalene, in human urine samples. Extracted VOCs from the human urine were effectively separated by GC using a mid-polarity column (DB-35, 35% phenylmethylpolysiloxane) and monitored by MS using extracted ion monitoring (EIM) mode. RESULTS: Under the optimized method, the linearity of the calibration curves was greater than 0.993. The limits of detection (LODs) at a signal-to-noise (S/N) ratio of 3 were 0.3-0.6 ng/mL. The coefficients of variation were in the range of 0.1-9.7% for within-day variation and 0.2-14.2% for day-to-day variation. CONCLUSIONS: The method was shown to be rapid and simple for the simultaneous determination of VOCs with a wide range of polarities in human urine and it could be applied to monitoring and to biomedical investigations to check exposure to VOCs. Copyright © 2017 John Wiley & Sons, Ltd.
Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Solid Phase Microextraction/methods , Volatile Organic Compounds/urine , Humans , Limit of Detection , Linear Models , Reproducibility of Results , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purificationABSTRACT
The thermal conductivity of superlattice films is generally anisotropic and should be studied separately in the in-plane and cross-plane directions of the films. However, previous works have mostly focused on the cross-plane thermal conductivity because the electrons and phonons in the cross-plane direction of superlattice films may result in much stronger interface scattering than that in the in-plane direction. Nevertheless, it is highly desirable to perform systematic studies on the effect of interface formation in semiconducting superlattice films on both in-plane and cross-plane thermal conductivities. In this study, we determine both the in-plane and cross-plane thermal conductivities of Al2O3 (AO)/ZnO superlattice films grown by atomic layer deposition (ALD) on SiO2/Si substrates in the temperature range of 50-300 K by the four-point-probe 3-ω method. Our experimental results indicate that the formation of an atomic AO layer (0.82 nm) significantly contributes to the decrease of the cross-plane thermal conductivity of the AO/ZnO superlattice films compared with that of AO/ZnO thin films. The cross-plane thermal conductivity (0.26-0.63 W m-1 K-1 of the AO/ZnO superlattice films (with an AO layer of â¼0.82 nm thickness) is approximately â¼150%-370% less than the in-plane thermal conductivity (0.96-1.19 W m-1 K-1) of the corresponding film, implying significant anisotropy. This indicates that the suppression of the cross-plane thermal conductivity is mainly attributed to the superlattice, rather than the nanograin columnar structure in the films. In addition, we theoretically analyzed strong anisotropic behavior of the in-plane and cross-plane thermal conductivities of the AO/ZnO superlattice films in terms of temperature dependence.
ABSTRACT
BACKGROUND: The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients. METHODS: Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima. AVF maturation failure was defined as an AVF that could not be used successfully by the third month after its creation. RESULTS: The prevalence of body mass index ≥30 kg/m2 was 17%, and AVF maturation failure occurred in 28 (45%) patients. Patients within the highest leptin tertile showed significantly higher maturation failure rate, independent of age, gender, diabetes, and body mass index. On histologic examination, significant differences in intimal hyperplasia (13.3 ± 4.5 vs 18.2 ± 5.2 vs 30.3 ± 14.3 µm) and medial thickening (76.8 ± 23.7 vs 103.9 ± 33.6 vs 109.3 ± 36.5 µm) were observed across leptin tertiles. Similarly, medial fibrosis was most severe in the highest tertile. According to the immunohistochemical staining, most intimal cells were α-smooth muscle actin-positive, vimentin-positive, desmin-negative myofibroblasts. However, in the lowest tertile, desmin-positive contractile smooth muscle cells were also frequently observed, suggesting relatively slow phenotypic changes in this group. Furthermore, as leptin tertiles increased, the expression of leptin receptor in the luminal border of intima was significantly decreased. CONCLUSIONS: Obesity-related higher fistula maturation failure rate may be partly mediated by higher leptin level-associated pre-existing vascular diseases in end-stage renal disease patients. Decreased expression of leptin receptor may be related to this association.
Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Kidney Failure, Chronic/therapy , Leptin/blood , Obesity/blood , Renal Dialysis , Vascular Diseases/complications , Veins/surgery , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Body Mass Index , Female , Humans , Hyperplasia , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Male , Middle Aged , Obesity/complications , Obesity/diagnosis , Prospective Studies , Receptors, Leptin/analysis , Republic of Korea , Risk Factors , Treatment Failure , Up-Regulation , Vascular Diseases/blood , Vascular Diseases/diagnostic imaging , Vascular Diseases/pathology , Veins/chemistry , Veins/diagnostic imaging , Veins/pathologyABSTRACT
Studies aiming to significantly improve thermal properties, such as figure-of-merit, of silicon nanowires (SiNW) have focused on diameter reduction and surface or interface roughness control. However, the mechanism underlying thermal conductivity enhancement of roughness controlled NWs remains unclear. Here, we report a significant influence of stacking faults (SFs) on the lateral thermal conductivity of a single SiNW, using a combination of newly developed in situ spatially-resolved thermal resistance experiments and high-resolution transmission electron microscopy measurements. We used as-grown SiNWs tapered along the growth direction with progressively lower roughness and SFs density. The results clearly confirmed that both surface roughness and twins or SFs densities suppress the thermal conductivity of an individual SiNW. The results and measurement techniques presented here hold great potential for inspecting minute changes in thermal resistance along an individual SiNW, caused by induced SFs on the nanostructure, and for improving one-dimensional nanowire-based thermoelectric device performance.
ABSTRACT
OBJECTIVE: Successful arteriovenous fistula (AVF) maturation is often challenging in obese patients. Optimal initial intraoperative blood flow (IOBF) is essential for adequate AVF maturation. This study was conducted to elucidate the effect of obesity on IOBF and radiocephalic AVF maturation. METHODS: Patients with a newly created radiocephalic AVF were included (N = 252). Obesity was defined as a baseline body mass index (BMI) ≥25 kg/m(2), and primary maturation failure was defined as failure to use the AVF successfully by 3 months after its creation. IOBF was measured immediately after construction of the AVF with a VeriQ system (MediStim, Oslo, Norway). RESULTS: The mean BMI was 24.1 ± 3.9 kg/m(2), and the prevalence of obesity was 31.3%. Particularly, 8.3% (21 patients) had a BMI ≥30 kg/m(2). Primary maturation failure occurred in 100 patients (39.7%), and an IOBF <190 mL/min was closely associated with the risk of maturation failure (relative risk, 3.05; 95% confidence interval, 1.52-6.11). Compared with nonobese patients, obese subjects had a significantly higher prevalence of diabetes and elevated high-sensitivity C-reactive protein levels, whereas diameters of vessels were similar. When the patients were further divided into three groups as BMI <25, 25 to 29.9, and ≥30 kg/m(2), patients in the higher BMI group showed significantly lower IOBF and higher maturation failure rate. According to multivariate analysis, the statistically significant variables that determined maturation failure were obesity, previous vascular disease, increased high-sensitivity C-reactive protein levels, and IOBF <190 mL/min. CONCLUSIONS: Obese patients had a significantly lower IOBF, and both obesity and low IOBF contributed to the primary maturation failure of AVF. Obesity-associated inflammation and atherosclerosis might play roles in this association.
Subject(s)
Arteriovenous Fistula/physiopathology , Arteriovenous Shunt, Surgical , Blood Circulation/physiology , Obesity/physiopathology , Aged , Aged, 80 and over , Arteriovenous Fistula/etiology , Body Mass Index , C-Reactive Protein/analysis , Diabetes Mellitus/physiopathology , Female , Humans , Intraoperative Period , Male , Middle Aged , Radial Artery/surgeryABSTRACT
We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, -0.1-1.7; P = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [clinicaltrial.gov: NCT00950664]
Subject(s)
Acetylcholine Release Inhibitors/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Torticollis/drug therapy , Adult , Aged , Double-Blind Method , Drug Combinations , Female , Humans , Male , Middle Aged , Pain/etiology , Pain Measurement , Torticollis/complications , Treatment Outcome , Young AdultABSTRACT
In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Selective transduction has been thought to originate from the ability of ACh, over that of other organic cations, to trigger the subsequent channel-opening step. However, transitions to and from the open state were shown to be similar for agonists with widely different efficacies. By studying mutant AChRs, we show here that the ultimate closed-to-open transition is agonist-independent and preceded by two primed closed states; the first primed state elicits brief openings, whereas the second elicits long-lived openings. Long-lived openings and the associated primed state are detected in the absence and presence of an agonist, and exhibit the same kinetic signatures under both conditions. By covalently locking the agonist-binding sites in the bound conformation, we find that each site initiates a priming step. Thus, a change in binding-site conformation primes the AChR for channel opening in a process that enables selective activation by ACh while maximizing the speed and efficiency of the biological response.
Subject(s)
Movement , Receptors, Nicotinic/chemistry , Receptors, Nicotinic/metabolism , Animals , Cell Line , Disulfides/metabolism , Electric Conductivity , Humans , Kinetics , Models, Molecular , Nicotinic Agonists/pharmacology , Patch-Clamp Techniques , Protein Structure, Tertiary , Receptors, Nicotinic/genetics , Synaptic Transmission/physiology , TorpedoABSTRACT
Full automation with high purity for circulating tumor cell (CTC) isolation has been regarded as a key goal to make CTC analysis a "bench-to-bedside" technology. Here, we have developed a novel centrifugal microfluidic platform that can isolate the rare cells from a large volume of whole blood. To isolate CTCs from whole blood, we introduce a disc device having the biggest sample capacity as well as manipulating blood cells for the first time. The fully automated disc platform could handle 5 mL of blood by designing the blood chamber having a triangular obstacle structure (TOS) with lateral direction. To guarantee high purity that enables molecular analysis with the rare cells, CTCs were bound to the microbeads covered with anti-EpCAM to discriminate density between CTCs and blood cells and the CTCs being heavier than blood cells were only settled under a density gradient medium (DGM) layer. To understand the movement of CTCs under centrifugal force, we performed computational fluid dynamics simulation and found that their major trajectories were the boundary walls of the DGM chamber, thereby optimizing the chamber design. After whole blood was inserted into the blood chamber of the disc platform, size- and density-amplified cancer cells were isolated within 78 min, with minimal contamination as much as approximately 12 leukocytes per milliliter. As a model of molecular analysis toward personalized cancer treatment, we performed epidermal growth factor receptor (EGFR) mutation analysis with HCC827 lung cancer cells and the isolated cells were then successfully detected for the mutation by PCR clamping and direct sequencing.
Subject(s)
Cell Separation/instrumentation , Lab-On-A-Chip Devices , Neoplastic Cells, Circulating/pathology , Automation , Blood Cells , Cell Line, Tumor , Centrifugation, Density Gradient , DNA Mutational Analysis , ErbB Receptors/genetics , Humans , Microfluidics , Polymerase Chain Reaction , Precision MedicineABSTRACT
BACKGROUND AND PURPOSE: The extracapsular spread (ECS) of lymph node metastasis (LNM) reflects tumor aggressiveness and is associated with poor survival and risk of distant metastasis. In this study, we aimed to explore the prognostic significance of epithelial-mesenchymal transition (EMT) of ECS tumors in LNM of head and neck cancers. METHODS: We collected LNM samples from head and neck cancer patients (follow-up >2 years) and made 20 ECS(-): ECS(+) pairs (1:2) of LNM (N = 60), matched by the primary sites and by T and N classifications. Immunostaining of cytokeratin, E-cadherin, vimentin, and CD31 were performed and quantified to determine the epithelial-mesenchymal transition percent (EMT%), defined as vimentin(+)/cytokeratin(+) area of ECS. Univariate and multivariable analyses of clinic-pathologic factors, including EMT% of ECS, were conducted to identify the significant prognosticators. In addition, the anatomical relationship between CD31 vessels and ECS tumors was analyzed. RESULTS: Rather than the presence of ECS in LNM, higher EMT% (>50 %) of ECS strongly correlated with the worse overall and disease-free survival and had more frequent recurrence and distant dissemination in their clinical courses. ECS tumors intermingled closely with Ki-67(-) CD31(+) non-proliferating perinodal blood vessels. Particularly, vimentin(+) ECS areas exhibited a higher density of CD31(+) perinodal vessels than did vimentin(-) ECS. CONCLUSION: High EMT scores of ECS tumors in LNM predict an unfavorable prognosis and systemic dissemination more accurately than the simple presence of ECS in LNM in head and neck cancer patients.
Subject(s)
Epithelial-Mesenchymal Transition , Head and Neck Neoplasms/chemistry , Head and Neck Neoplasms/pathology , Lymph Nodes/blood supply , Cadherins/analysis , Disease-Free Survival , Female , Humans , Keratins/analysis , Ki-67 Antigen/analysis , Lymphatic Metastasis , Male , Neoplasm Staging , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Survival Rate , Vimentin/analysisABSTRACT
Although the frequent spontaneous resolution of contact granuloma is reported, the prognostic factor that can predict the possibility of resolution is not clear. We retrospectively analyzed the hospital records and laryngoscopic photos of 52 patients who were diagnosed with contact granuloma between May 2003 and June 2012. The reflux finding score and the shape of the granuloma were analyzed based on the initial laryngoscopy images; additionally, age, gender, chief complaint, and the side afflicted were also analyzed. Of the 52 patients, 40 who were treated conservatively were analyzed. Their mean age was 57.6 years and the mean follow-up period was 28.6 weeks. There was male predominance (87.5%), and the left side was more commonly afflicted (60.0%). Factors significantly associated with resolution included width/height ratio (P = 0.012) and gender (P = 0.048), but not reflux finding score (P = 0.713) or etiology (P = 0.382). So with this data, resolution of contact granuloma is highly probable in cases where the granuloma has a narrow base and the gender is female.
Subject(s)
Granuloma/pathology , Laryngeal Diseases/pathology , Adult , Aged , Female , Follow-Up Studies , Granuloma/etiology , Humans , Laryngeal Diseases/etiology , Laryngoscopy , Male , Middle Aged , Prognosis , Remission, Spontaneous , Retrospective Studies , Sex FactorsABSTRACT
Tracing fast nanopore-translocating analytes requires a high-frequency measurement system that warrants a temporal resolution better than 1 µs. This constraint may practically shift the challenge from increasing the sampling bandwidth to dealing with the rapidly growing noise with frequencies typically above 10 kHz, potentially making it still uncertain if all translocation events are unambiguously captured. Here, a numerical simulation model is presented as an alternative to discern translocation events with different experimental settings including pore dimension, bias voltage, the charge state of the analyte, salt concentration, and electrolyte viscosity. The model allows for simultaneous analysis of forces exerting on a large analyte cohort along their individual trajectories; these forces are responsible for the analyte movement leading eventually to the nanopore translocation. Through tracing the analyte trajectories, the Brownian force is found to dominate the analyte movement in electrolytes until the last moment at which the electroosmotic force determines the final translocation act. The mean dwell time of analytes mimicking streptavidin decreases from ≈6 to ≈1 µs with increasing the bias voltage from ±100 to ±500 mV. The simulated translocation events qualitatively agree with the experimental data with streptavidin. The simulation model is also helpful for the design of new solid-state nanopore sensors.
ABSTRACT
Herein, sol-gel-processed Y2O3 resistive random-access memory (RRAM) devices were fabricated. The top electrodes (TEs), such as Ag or Cu, affect the electrical characteristics of the Y2O3 RRAM devices. The oxidation process, mobile ion migration speed, and reduction process all impact the conductive filament formation of the indium-tin-oxide (ITO)/Y2O3/Ag and ITO/Y2O3/Cu RRAM devices. Between Ag and Cu, Cu can easily be oxidized due to its standard redox potential values. However, the conductive filament is easily formed using Ag TEs. After triggering the oxidation process, the formed Ag mobile metal ions can migrate faster inside Y2O3 active channel materials when compared to the formed Cu mobile metal ions. The fast migration inside the Y2O3 active channel materials successfully reduces the SET voltage and improves the number of programming-erasing cycles, i.e., endurance, which is one of the nonvolatile memory parameters. These results elucidate the importance of the electrochemical properties of TEs, providing a deeper understanding of how these factors influence the resistive switching characteristics of metal oxide-based atomic switches and conductive-metal-bridge-filament-based cells.