A highly selective and stable cationic polyelectrolyte encapsulated black phosphorene based impedimetric immunosensor for Interleukin-6 biomarker detection.

Due to the insufficiency of binding sites for the immobilized recognition biomolecules on the immunosensing platform, cancer detection becomes challenging. Whereas, the degradation of black phosphorene (BP) in the presence of the environmental factors becomes a concerning issue for use in electrochemical sensing. In this study, BP is successfully encapsulated by polyallylamine (PAMI) to increase its stability as well as to enhance its electrochemical performance. The successful encapsulation of BP is ensured through X-ray Photoelectron spectroscopy and Raman spectroscopy, whereas the stability of black phosphorus is ensured by Zeta potential measurements and cyclic voltammetry tests. The developed BP-PAMI composite showed high stability in the ambient environment and exhibited improved electrochemical performances. The impedimetric immunosensor was developed on a BP-PAMI modified laser burned graphene (LBG) to detect interleukin-6 biomarkers using electrochemical impedance spectroscopy (EIS). Under the optimized parameters, the fabricated immunosensor demonstrated a wide linear range of 0.003-75 ng/mL, limit of detection (LOD) of 1 pg/mL. Based on the experimental analysis, the developed sensing strategy can be employed as an easy, disposable, cost-effective and highly selective point-of-care cancer detection. In addition, the developed technique can be applied broadly for detecting other biomarkers after treating with suitable biomolecules.

Smart bandage with integrated multifunctional sensors based on MXene-functionalized porous graphene scaffold for chronic wound care management.

Three-dimensional (3D) porous laser-guided graphene (LGG) electrodes on elastomeric substrates are of great significance for developing flexible functional electronics. However, the high sheet resistance and poor mechanical properties of LGG sheets obstruct their full exploitation as electrode materials. Herein, we applied 2D MXene nanosheets to functionalize 3D LGG sheets via a C-O-Ti covalent crosslink to obtain an LGG-MXene hybrid scaffold exhibited high conductivity and improved electrochemistry with fast heterogeneous electron transfer (HET) rate due to the synergistic effect between LGG and MXene. Then we transferred the obtained hybrid scaffold onto PDMS to engineer a smart, flexible, and stretchable multifunctional sensors-integrated wound bandage capable of assessing uric acid (UA), pH, and temperature at the wound site. The integrated UA sensor exhibited a rapid response toward UA in an extended wide range of 50-1200 µM with a high sensitivity of 422.5 µA mM-1 cm-2 and an ultralow detection limit of 50 µM. Additionally, the pH sensor demonstrated a linear Nernstian response (R2 = 0.998) with a high sensitivity of -57.03 mV pH-1 in the wound relevant pH range of 4-9. The temperature sensor exhibited a fast and stable linear resistive response to the temperature variations in the physiological range of 25-50 °C with an excellent sensitivity and correlation coefficient of 0.09% °C-1 and 0.999, respectively. We anticipate that this stretchable and flexible smart bandage could revolutionize wound care management and have profound impacts on the therapeutic outcomes.

High-Performance Flexible Electrochemical Heavy Metal Sensor Based on Layer-by-Layer Assembly of Ti3C2Tx/MWNTs Nanocomposites for Noninvasive Detection of Copper and Zinc Ions in Human Biofluids.

A flexible electrochemical heavy metal sensor based on a gold (Au) electrode modified with layer-by-layer (LBL) assembly of titanium carbide (Ti3C2Tx) and multiwalled carbon nanotubes (MWNTs) nanocomposites was successfully fabricated for the detection of copper (Cu) and zinc (Zn) ions. An LBL drop-coating process was adopted to modify the surface of Au electrodes with Ti3C2Tx/MWNTs treated via ultrasonication to fabricate this novel nanocomposite electrode. In addition, an in situ simultaneous deposition of "green metal" antimony (Sb) and target analytes was performed to improve the detection performance further. The electrochemical measurement was realized using square wave anodic stripping voltammetry (SWASV). Moreover, the fabricated sensor exhibited excellent detection performance under the optimal experimental conditions. The detection limits for Cu and Zn are as low as 0.1 and 1.5 ppb, respectively. Furthermore, Cu and Zn ions were successfully detected in biofluids, that is, urine and sweat, in a wide range of concentration (urine Cu: 10-500 ppb; urine Zn: 200-600 ppb; sweat Cu: 300-1500 ppb; and sweat Zn: 500-1500 ppb). The fabricated flexible sensor also possesses other advantages of ultra-repeatability and excellent stability. Thus, these advantages provide a great possibility for the noninvasive smart monitoring of heavy metals in the future.

Highly flexible and conductive poly (3, 4-ethylene dioxythiophene)-poly (styrene sulfonate) anchored 3-dimensional porous graphene network-based electrochemical biosensor for glucose and pH detection in human perspiration.

The patterned LIG flakes are generally not interconnected due to the line gap of the laser ray, leading to lower uniform conductivity and fragile graphene. Thus, the fabrication of a highly conductive and mechanically robust LIG-based biosensing platform remains challenging. In this study, the fabrication of a flexible electrochemical biosensor is reported based on poly (3, 4-ethylene dioxythiophene)-poly (styrene sulfonate) (PEDOT:PSS) modified 3-dimensional (3D) stable porous laser-induced graphene (LIG) for the detection of glucose and pH. PEDOT:PSS was spray-coated on the LIG to improve electrode robustness and deliver uniform electrical conductivity. The as-prepared PEDOT:PSS modified LIG (PP/LIG) was characterized using field-emission scanning electron microscopy (FESEM), x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and Fourier-transform infrared spectroscopy (FTIR). Platinum and palladium nanoparticles (Pt@Pd) were successfully electrodeposited on PP/LIG, markedly enhancing the electrocatalytic activity for glucose detection. The fabricated biosensor exhibited an excellent amperometric response to glucose with a wide linear range of 10 µM - 9.2 mM, a high sensitivity of 247.3 µAmM-1cm-2, and a low detection limit (LOD) of 3 µM, with high selectivity. In addition, the pH sensor was functionalized by the polyaniline (PANI) on PP/LIG, and it also exhibited excellent potentiometric response with a high sensitivity of 75.06 mV/pH in the linear range of pH 4 - 7. Ultimately, the feasibility of the biosensor was confirmed by the analysis of human perspiration collected during physical exercise. This approach validates the utility of the novel fabrication procedure, and the potential of the LIG-conductive polymer composite for biosensing applications.

Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma.

BACKGROUND AND OBJECTIVE: The neurotransmitter, 5-hydroxytryptamine, acts as an immunomodulator by stimulating the release of inflammatory cytokines and regulating the function of dendritic cells and monocytes. The 5-hydroxytryptamine receptor 4 (HTR4) gene is located in a region previously linked to an increased risk of asthma and atopy. The aim of this study was to investigate the association between HTR4 and asthma. METHODS: Thirty-two single nucleotide polymorphisms (SNP) in HTR4 were investigated by direct sequencing of 24 DNA samples from unrelated Korean subjects. RESULTS: The 32 genetic variants comprised 22 intronic SNP, two SNP in the 3'-untranslated region (exon 7) and eight SNP in the 3'-downstream region. Logistic regression analysis showed that two intronic polymorphisms were significantly associated with the risk of asthma. Two minor HTR4 alleles, +142828G>A and +122769G>A, occurred at significantly higher frequencies in the asthmatic group than in the healthy control group (49.59% vs 42.29%, P=0.003, and 47.99% vs 40.35%, P=0.008, respectively), and these differences remained significant after correction for multiple testing (P=0.05, dominant mode of inheritance; and P=0.03, dominant mode, respectively). Haplotype analysis revealed three haplotype blocks. The frequency of haplotype 1 in block 2 was significantly higher in asthmatics (P=0.003, dominant mode), whereas the frequency of haplotype 4 in block 3 was significantly lower in asthmatics (P=0.0009, dominant mode). CONCLUSIONS: SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma.

Relationship between group-specific component protein and the development of asthma.

RATIONALE: Airway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins. OBJECTIVES: To search for asthma-specific proteins in bronchoalveolar lavage fluid (BAL) from individuals with asthma and to validate the identified proteins in an experimental model of asthma. METHODS: Liquid chromatography-tandem mass spectrometry was performed to identify proteins in BAL fluid found by two dimensional electrophoresis (2DE) to be differentially expressed in subjects with asthma versus control subjects. Group-specific component (Gc) and mRNA levels were measured using an ELISA, Western blots, and PCR. A neutralization study using an antibody against Gc protein was performed in an experimental asthma model. MEASUREMENTS AND MAIN RESULTS: Based on 2DE, 15 proteins were significantly up-regulated or down-regulated in eight subjects with asthma compared with eight control subjects. The protein levels of Gc, hemopexin, and haptoglobin-b were increased, whereas the a1- antitrypsin and glutathione S-transferase levels were decreased in subjects with asthma. The Gc concentration in BAL fluid was significantly elevated in 67 subjects with asthma compared with that in 22 control subjects (P < 0.009). The Gc was significantly correlated with the neutrophil percentage in BAL fluid of subjects with asthma (P = 0.001). Gc mRNA and protein levels were higher in ovalbumin-sensitized/ challenged asthma mice than in sham-treated mice. Gc protein were expressed on alveolar macrophages and on epithelial cells. Treatment with an anti-Gc antibody dose-dependently reduced the ovalbumin sensitization/challenge-induced enhancement of airway hyperreactivity, airway inflammation, goblet cell hyperplasia,and levels of eotaxin, interleukin-4, -5, and -13, and interferon-g. CONCLUSIONS: Gc may be involved in the development of asthma, and the neutralization of Gc protein could be a therapeutic strategy for asthma.

Association of SLC6A12 variants with aspirin-intolerant asthma in a Korean population.

Aspirin-intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin-intolerant asthma (AIA) and 429 aspirin-tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P= 0.005; P(corr)= 0.03), rs557881 (non-synonymous C10R, P= 0.007; P(corr)= 0.04), and SLC6A12_BL1_ht1 (P= 0.009; P(corr)= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV(1) by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.

Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk.

Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells.

A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31-32 region and asthma.

The human chromosomal 5q31-33 region has been implicated as a susceptibility locus for several immune-mediated diseases including asthma in several populations. Recently, the extraneuronal GABAergic system has been implicated as a new link to airway obstruction in asthma. In addition, the SLC6A7 gene, which is positioned at 5q31-32 and encodes the transporter for an excitatory neurotransmitter of L-proline, has never been studied for its association with asthma. In this study, resequencing of all exon, promoter region (2 kb), and exon-intron boundary regions in the SLC6A7 gene found a total of 33 single nucleotide polymorphisms (SNPs) in 24 Korean asthmatic patients. After the initial SNP survey, a total of 17 common SNPs with minor allele frequency (MAF) over 10% were genotyped in 498 asthmatic patients and 303 normal controls. Logistic analyses revealed significant associations between genetic variants of the SLC6A7 gene and asthma (P-value up to 6.0 x 10(-4); P(corr) value up to 0.009). In further regression analyses, minor alleles of intronic +11431T>C, +12213C>T and +12927A>G in linkage disequilibrium block 2 and +20113T>C in 3'UTR significantly increased the bronchodilator response in asthmatics (P-value of recessive model up to 0.008; which are not significant after multiple correction). Therefore, our findings suggest that SLC6A7 could be a susceptible gene for asthma.