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Functionalized graphene oxide is a novel type of highly efficient biosensing material. In this study, we present a carboxyl-functionalized graphene oxide (GO-COOH)-based surface ...plasmon resonance (SPR) chip for the rapid and quantitative detection of non-small cell lung carcinoma (NSCLC) via the cytolerayin 19 (CK19) protein biomarker in spiked human plasma. We demonstrated the binding specificity of kinetic analysis of interactions between GO-COOH and anti-CK19 and CK19 protein. We also calculated the relationship between the SPR angle and refractive index of GO-COOH, and demonstrated that COOH modified GO sheets on Au film can enhance the field energy propagation intensity of an SPR sensor, resulting in a higher sensitivity for the detection of CK19 protein compared to a conventional Au-based SPR chip. The immunosensor was constructed and engineered by immobilizing a low concentration (10 μg/mL) of CK19 antibody on an SPR chip. The lowest detectable concentration was as low as 1 fg/mL. A spiked 10% human plasma CK19 detection limit of 0.05 pg/mL was achieved, well below the normal physiological level of serum protein (3.3 ng/mL). Therefore, a carboxyl-GO based SPR biosensor appears to have high sensitivity and specificity for the detection of clinical whole plasma biomarkers and possible application in diagnosing diseases.
Several studies suggest that glial scars pose as physical and chemical barriers that limit neurite regeneration after spinal cord injury (SCI). Evidences suggest that the activation of the ...PI3K/Akt/mTOR signaling pathway is involved in glial scar formation. Therefore, inhibition of the PI3K/Akt/mTOR pathway may beneficially attenuate glial scar formation after SCI. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates the PI3K/Akt/mTOR pathway. Therefore, we hypothesized that the overexpression of PTEN in the spinal cord will have beneficial effects after SCI. In the present study, we intrathecally injected a recombinant adenovirus carrying the pten gene (Ad-PTEN) to cause overexpression of PTEN in rats with contusion injured spinal cords. The results suggest overexpression of PTEN in spinal cord attenuated glial scar formation and led to improved locomotor function after SCI. Overexpression of PTEN following SCI attenuated gliosis, affected chondroitin sulfate proteoglycan expression, and improved axon regeneration into the lesion site. Furthermore, we suggest that the activation of the PI3K/Akt/mTOR pathway in astrocytes at 3days after SCI may be involved in glial scar formation. Because delayed treatment with Ad-PTEN enhanced motor function recovery more significantly than immediate treatment with Ad-PTEN after SCI, the results suggest that the best strategy to attenuate glial scar formation could be to introduce 3days after SCI. This study's findings thus have positive implications for patients who are unable to receive immediate medical attention after SCI.
•I.t. Ad vector overexpression of astrocytic PTEN in normal and injured spinal cord.•Overexpression of PTEN following SCI led to improved locomotor function after SCI.•Overexpression of PTEN following SCI attenuated the glial scar formation.•Activation of the PI3K/Akt/mTOR pathway may be involved in glial scar formation.
The surface plasmon resonance (SPR) biosensor has become a powerful analytical tool for investigating biomolecular interactions. There are several methods to excite surface plasmon, such as coupling ...with prisms, fiber optics, grating, nanoparticles, etc. The challenge in developing this type of biosensor is to increase its sensitivity. In relation to this, graphene is one of the materials that is widely studied because of its unique properties. In several studies, this material has been proven theoretically and experimentally to increase the sensitivity of SPR. This paper discusses the current development of a graphene-based SPR biosensor for various excitation methods. The discussion begins with a discussion regarding the properties of graphene in general and its use in biosensors. Simulation and experimental results of several excitation methods are presented. Furthermore, the discussion regarding the SPR biosensor is expanded by providing a review regarding graphene-based Surface-Enhanced Raman Scattering (SERS) biosensor to provide an overview of the development of materials in the biosensor in the future.
Pyroptosis is a form of regulated cell death mediated by gasdermin family members, among which the function of GSDMC has not been clearly described. Herein, we demonstrate that the metabolite ...α-ketoglutarate (α-KG) induces pyroptosis through caspase-8-mediated cleavage of GSDMC. Treatment with DM-αKG, a cell-permeable derivative of α-KG, elevates ROS levels, which leads to oxidation of the plasma membrane-localized death receptor DR6. Oxidation of DR6 triggers its endocytosis, and then recruits both pro-caspase-8 and GSDMC to a DR6 receptosome through protein-protein interactions. The DR6 receptosome herein provides a platform for the cleavage of GSDMC by active caspase-8, thereby leading to pyroptosis. Moreover, this α-KG-induced pyroptosis could inhibit tumor growth and metastasis in mouse models. Interestingly, the efficiency of α-KG in inducing pyroptosis relies on an acidic environment in which α-KG is reduced by MDH1 and converted to L-2HG that further boosts ROS levels. Treatment with lactic acid, the end product of glycolysis, builds an improved acidic environment to facilitate more production of L-2HG, which makes the originally pyroptosis-resistant cancer cells more susceptible to α-KG-induced pyroptosis. This study not only illustrates a pyroptotic pathway linked with metabolites but also identifies an unreported principal axis extending from ROS-initiated DR6 endocytosis to caspase-8-mediated cleavage of GSDMC for potential clinical application in tumor therapy.
The proliferation of drug-resistant pathogens continues to increase, giving rise to serious public health concerns. Many researchers have formulated metal oxide nanoparticles for use as novel ...antibacterial agents. In the present study, copper oxide (CuO) was synthesized by simple hydrothermal synthesis, and doping was performed to introduce different polymers onto the NP surface for bacteriostasis optimization. The polymer-modified CuO NPs were analyzed further with XRD, FTIR, TEM, DLS and zeta potential to study their morphology, size, and the charge of the substrate. The results indicate that polymer-modified CuO NPs had a significantly higher bacteriostatic rate than unmodified CuO NPs. In particular, polydopamine (PDA)-modified CuO (CuO-PDA) NPs, which carry a weakly negative surface charge, exhibited excellent antibacterial effects, with a bacteriostatic rate of up to 85.8 ± 0.2% within 3 h. When compared to other polymer-modified CuO NPs, CuO-PDA NPs exhibited superior bacteriostatic activity due to their smaller size, surface charge, and favorable van der Waals interactions. This may be attributed to the fact that the CuO-PDA NPs had relatively lipophilic structures at pH 7.4, which increased their affinity for the lipopolysaccharide-containing outer membrane of the Gram-negative bacterium
The development of functionalized molybdenum disulfide (MoS2) has led to a new trend in the biosensing field, owing to its high sensitivity and bio-affinity characteristics with regards to the simple ...synthesis of carboxyl-functionalized MoS2 nanocomposites. In this study, we used monochloroacetic acid (MCA) to successfully modify carboxyl-MoS2. The efficiency of this MCA modification method showed a higher -COOH group content of 30.1%, mainly due to chlorine atoms occupying the MoS2 sulfur vacancy to allow for the formation of a strong bonding effect. This then enhanced the surface area of -COOH and improved the formation of covalent bonds between proteins. We demonstrated that MoS2-COOH-based surface plasmon resonance (SPR) chips can provide excellent sensitivity and high affinity for immunoassay biomolecules detected in a low sample volume of 20 μl. With respect to the shifts of the SPR angles of the chips, the high binding affinity at a BSA concentration of 14.5 nM for a MoS2-COOH chip, a MoS2 chip and a traditional SPR chip are 4.69 m°, 2.49 m° and 1.53 m°, respectively. In addition, the MoS2-COOH chip could amplify the SPR angle response by 3.1 folds and enhance the high association rate of ka by 212 folds compared to MoS2 and traditional SPR chips. The results thus obtained revealed that the overall affinity binding value, KA, of the MoS2-COOH chip can be significantly enhanced by up to ∼ 6.5 folds that of the MoS2 chip. In summary, the excellent binding affinity, biocompatible and high sensitivity suggest the potential of the clinical application of this MoS2-COOH-based SPR chip detection method for in vitro diagnostic and point-of-care testing devices.
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•This work demonstrates the excellent potential of SPR-based biosensors to generate MoS2-COOH as biocompatible surfaces on sensing films.•The affinity binding of the MoS2-COOH chip can be significantly enhanced by up to ∼ 6.5 folds that of the MoS2 chip.•The MoS2-COOH chip could amplify the SPR angle response by 3.1 folds and enhance the high association rate of ka by 212 folds compared to MoS2 and traditional SPR chips.
Angiosperms are by far the most species-rich clade of land plants, but their origin and early evolutionary history remain poorly understood. We reconstructed angiosperm phylogeny based on 80 genes ...from 2,881 plastid genomes representing 85% of extant families and all orders. With a well-resolved plastid tree and 62 fossil calibrations, we dated the origin of the crown angiosperms to the Upper Triassic, with major angiosperm radiations occurring in the Jurassic and Lower Cretaceous. This estimated crown age is substantially earlier than that of unequivocal angiosperm fossils, and the difference is here termed the 'Jurassic angiosperm gap'. Our time-calibrated plastid phylogenomic tree provides a highly relevant framework for future comparative studies of flowering plant evolution.
The most commonly used protein detection methods in clinical diagnosis and disease monitoring are enzyme-linked immunosorbent assay (ELISA), Western blotting (immunoblot), and lateral flow assay ...(LFA) rapid screening, of which ELISA is the gold standard immunoassay in clinical practice ...
In this study, we demonstrate the fabrication of graphene oxide sheet (GOS)-based surface plasmon resonance (SPR) sensors for protein immobilization detection. GOS was used as the medium owing to its ...high covalent binding affinity for proteins. We were able to monitor the binding phenomenon in real time using the SPR-based technique. Thus, this GOS sensor can detect bovine albumin serum (BSA) directly in GOS films and exhibited up to a 4.3-fold higher angle shift than that of the conventional Au/Cr-based sensor in 10ng/ml of BSA. The results showed that the SPR biosensor formed using a GOS solution of 2mg/ml has optimal sensitive and had a BSA detection limit as low as 100pg/ml. The sensitivity of the slope ratio of the GOS vs. conventional Au substrate is 2.4:1. Moreover, GOS is a label-free detection without additional amplification steps to enhance the sensitivity. In addition, the average value of the affinity binding constant KA for the GOS-based sensor with respect to BSA was 80.8×106M−1. These results suggest that GOS-based SPR biosensors have potential for use in high-sensitivity protein immobilization detection.
Gold nanoparticles (AuNPs) have been widely used for various applications because of their unique properties. In this study, theoretical and experimental studies have been carried out to study the ...signal characteristics of the AuNPs-based localized surface plasmon resonance (LSPR) immunosensor. The finite-difference time domain (FDTD) method has been chosen to obtain information regarding optical properties and electric field profiles of AuNPs with different structures and configurations. The simulation results show that the distance between particles greatly affects the extinction and scattering spectra. In addition, there was a significant enhancement in the electric field due to the presence of dielectric material on the surface of AuNPs. In the case of dimer nanoparticles, the enhancement of the electric field is up to 20 times higher than that of single AuNPs. Experimentally, the enhancement of the electric field causes the detection range of the sensor to be limited. From the different concentrations of bovine serum albumin (BSA) investigated, the sensor is only able to detect BSA from 1 ng/mL to <inline-formula> <tex-math notation="LaTeX">10 \mu \text{g} </tex-math></inline-formula>/mL. We encountered the Hook effect in this experiment which was characterized by a decrease in the LSPR signal at a concentration of <inline-formula> <tex-math notation="LaTeX">100 \mu \text{g} </tex-math></inline-formula>/mL. A thicker dielectric layer can enhance the electric field around the nanoparticles and as a result, interference from changes in refractive index (RI) originating from other materials around the nanoparticles becomes difficult to avoid.
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