Galvanic Redox Potentiometry for Fouling-Free and Stable Serotonin Sensing in a Living Animal Brain.

Serotonin (5-HT) is a major neurotransmitter broadly involved in many aspects of feeling and behavior. Although its electro-activity makes it a promising candidate for electrochemical sensing, the persistent generation of fouling layers on the electrode by its oxidation products presents a hurdle for reliable sensing. Here, we present a fouling-free 5-HT sensor based on galvanic redox potentiometry. The sensor efficiently minimizes electrode fouling as revealed by in situ Raman spectroscopy, ensuring a less than 3 % signal change in a 2 hour continuous experiment, whereas amperometric sensors losing 90 % within 30 min. Most importantly, the sensor is highly amenable for in vivo studies, permitting real-time 5-HT monitoring, and supporting the mechanism associated with serotonin release in brain. Our system offers an effective way for sensing different neurochemicals having significant fouling issues, thus facilitating the molecular-level understanding of brain function.

Electrochemical Conjugation of Aptamers on a Carbon Fiber Microelectrode Enables Highly Stable and Selective In†Vivo Neurosensing.

Interfacing aptamers with carbon fiber microelectrodes (CFEs) provides a versatile platform to probe the chemical activity in a living brain at the molecular level. However, new approaches are needed for the efficient and stable modification of electrode surfaces with aptamers. Here, we present an electrochemical conjugation strategy to covalently couple aptamers onto CFEs with high chemoselectivity, efficiency, and stability for sensing in the brain. The strategy employs an initial electrochemical coupling of catechol on an CFE, thereby generating a thin layer of quinone intermediates that couple rapidly with thiol-containing oligonucleotides under a controlled potential. This approach dramatically simplifies and improves the efficiency for modifying carbon surfaces, thereby allowing direct conjugation of high levels of aptamers on CFEs within 5 minutes. Importantly, the covalent linkage between the aptamers and carbon surfaces enables a greatly improved sensitivity and stability for the sensing of dopamine, offering a robust system for continuously probing dopamine dynamics in the living brains of animals.

A copper-based metal-organic framework/graphene nanocomposite for the sensitive and stable electrochemical detection of DNA bases.

A simple and easy-operation electrode modification strategy was proposed using Cu-MOF/GO nanohybrids for physiologists and pathologists for the feasible and reliable simultaneous electrochemical detections of DNA bases, namely guanine and adenine. The nanohybrids were prepared via a simple ultrasonic method and were employed for the fabrication of a sensing interface. SEM, TEM, XRD, FT-IR, and electrochemical characterizations were used to characterize the general morphology and structure of the nonohybrids. The proposed Cu-MOF/ERGO/GCE exhibited ultra-stable and high-sensitivity performance in the simultaneous electrochemical detection of guanine and adenine. The recorded DPV curves revealed a linear increase in the faradaic signals with increase in the concentrations of guanine and adenine in the range of 0.02-10 µM and 20-100 µM for guanine, and 0.005-20 µM and 40-200 µM for adenine. The relative standard deviation of guanine and adenine for 50 consecutive detections is 1.37% and 1.92%, respectively. It was proved that the proposed Cu-MOF/ERGO/GCE can be performed for the detection of guanine and adenine in real samples, such as Herring sperm DNA, and satisfactory results were obtained. This strategy does not require complicated modification procedures, professional modification techniques, or sophisticated instruments, but it can provide a highly sensitive and stable detection method, which is expected to expand and deepen the applications of electrochemical detection in life science research.

Aptamer-Based Potentiometric Sensor Enables Highly Selective and Neurocompatible Neurochemical Sensing in Rat Brain.

Selective and nondisruptive in vivo neurochemical monitoring within the central nervous system has long been a challenging endeavor. We introduce a new sensing approach that integrates neurocompatible galvanic redox potentiometry (GRP) with customizable phosphorothioate aptamers to specifically probe dopamine (DA) dynamics in live rat brains. The aptamer-functionalized GRP (aptGRP) sensor demonstrates nanomolar sensitivity and over a 10-fold selectivity for DA, even amidst physiological levels of major interfering species. Notably, conventional sensors without the aptamer modification exhibit negligible reactivity to DA concentrations exceeding 20 µM. Critically, the aptGRP sensor operates without altering neuronal activity, thereby permitting real-time, concurrent recordings of both DA flux and electrical signaling in vivo. This breakthrough establishes aptGRP as a viable and promising framework for the development of high-fidelity sensors, offering novel insights into neurotransmission dynamics in a live setting.

Reasonable design of an MXene-based enzyme-free amperometric sensing interface for highly sensitive hydrogen peroxide detection.

Sensitive detection of H2O2 in the nano- to micromolar range is critical for health monitoring and disease diagnosis. Two-dimensional transition metal carbides or/and nitrides (called MXenes, MXs) have excellent potential applications in the electrochemical field due to their outstanding electrical conductivity and catalytic properties. In this work, Ti3C2Tx (MX) was employed for the construction of a sensitive and enzyme-free electrochemical sensing interface for the detection of hydrogen peroxide (H2O2) through a simple and effective method. Prussian blue (PB) was electrochemically deposited on the surface of a glassy carbon electrode (GCE). Chitosan (CS) and MX were sequentially dripped onto the PB modified GCE surface. The reasonable fabrication of the MX/CS/PB/GCE sensing interface presented good electrochemical sensing performance towards H2O2 with a low limit of detection (4 nM), a wide linear range from 50 nM to 667 µM and good selectivity. The proposed MX/CS/PB/GCE has been proven to monitor H2O2 in food samples and biological samples with recoveries between 94.7% and 100.3%. This work has made a beneficial attempt and research for exploring and expanding the application of MXs in the field of electrochemical sensing.

Glycyrrhizin suppresses inflammation and cell apoptosis by inhibition of HMGB1 via p38/p-JUK signaling pathway in attenuating intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is associated with the nucleus pulposus (NP) cells inflammation and apoptosis. Previous studies have shown that glycyrrhizin (GL) is a valid inhibitor of the high-mobility group box-1 gene (HMGB1) which expressed much higher in an inflammatory condition. However, it is not known whether GL protects against IDD by the inhibition of HMGB1. To study the effect and mechanism of glycyrrhizin on intervertebral disc degeneration. We analyzed the expression of HMGB1 in different degree of degenerate disc tissues. Interleukin 1 beta (IL-1ß) was used in stimulating the NP cells to degeneration. We used recombined human HMGB1 to resist the function of GL to explore whether GL acted via the target of HMGB1. Our study showed that the expression of HMGB1 markedly increased in severely degenerated disc tissues. IL-1ß promoted the progress of IDD, and the stimulation of GL could reverse the effects of IL-1ß. Moreover, p38 and p-JNK were significantly suppressed by GL stimuli. These results suggested that GL prevented NP degradation via restraining inflammation and cell apoptosis by inhibition of HMGB1 via p38/p-JNK signaling pathway. GL may become a novel cytokine for the therapy of IDD in the future.

Covalent Functionalization of Graphene Oxide with a Presynthesized Metal-Organic Framework Enables a Highly Stable Electrochemical Sensing.

This paper reports the covalent functionalization of graphene oxide (GO) by a presynthesized metal-organic framework NH2-MIL-101(Fe) via ultrasonication of the two components. The formation of Fe-O covalent bonding in the NH2-MIL-101(Fe)-GO nanohybrid is clearly evidenced, and the covalent bonding still remains after electrochemical reduction. The morphology and structure of the nanohybrid are characterized via scanning electron microscopy, transmission electron microscopy, UV-vis spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy. The electrode based on electrochemically reduced NH2-MIL-101(Fe)-GO shows ultrastable and high-sensitive performance in simultaneous electrochemical sensing of three purine metabolic derivatives (uric acid, xanthine, and hypoxanthine); in particular, no signal fading is seen even after running for 120 times. The covalent bonding within the nanohybrid is obviously the key to maintain such a stability.

Research on the function and related mechanism of P27 gene in the intervertebral disc degeneration of mice.

This study aims to investigate the function and related mechanism of P27 gene in intervertebral disc (IVD) degeneration of mice. X-ray, immunohistochemical staining, and alkaline phosphatase (ALP) histochemical staining were used to analyze the phenotypic difference of the intervertebral discs of 4-week-old mice with P27 gene knockout (P27-/-) and wild-type (WT) mice in the same brood. Protein in the intervertebral disc was extracted and western blot analysis was employed to detect the changes in the expression of related molecules in the Shh-signal pathways, including Shh, Patched, Smoothened and Gli2. As a result, the ALP histochemical staining revealed that the ALP-positive area of mice in the P27-/- group was obviously increased compared to the 4-week-old mice of the same brood in the WT group. In addition, the Col-I immunohistochemical staining showed that the Col-I-positive area of mice in the P27-/- group was significantly increased compared to mice in the WT group. Furthermore, Smo-positive cell rate of mice in the P27-/- group was apparently increased compared to mice in the WT group. Western blot analysis revealed that in terms of changes of protein expression levels of Shh, Patched, Smoothened and Gli2 in the intervertebral disc, protein expression levels of Shh, Patched, Smoothened and Gli2 of mice in the P27-/- group were significantly increased compared to those of mice in the WT group. The results show that P27 deficiency activates the expression of Shh-signal pathway and promotes the proliferation of osteoblast, thus, playing a role in promoting IVD degeneration, which provides a scientific and reliable experimental basis for the treatment of the IVD degeneration-related diseases in clinical practice.

Identifying and characterizing key nodes among communities based on electrical-circuit networks.

Complex networks with community structures are ubiquitous in the real world. Despite many approaches developed for detecting communities, we continue to lack tools for identifying overlapping and bridging nodes that play crucial roles in the interactions and communications among communities in complex networks. Here we develop an algorithm based on the local flow conservation to effectively and efficiently identify and distinguish the two types of nodes. Our method is applicable in both undirected and directed networks without a priori knowledge of the community structure. Our method bypasses the extremely challenging problem of partitioning communities in the presence of overlapping nodes that may belong to multiple communities. Due to the fact that overlapping and bridging nodes are of paramount importance in maintaining the function of many social and biological networks, our tools open new avenues towards understanding and controlling real complex networks with communities accompanied with the key nodes.

Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.

HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.