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A Faraday-cage-type electrochemical aptasensor based on two-dimensional (2D) nanomaterials was developed for the sensitive detection of Escherichia coli O157:H7. In this electrochemical aptasensor, 2D titanium carbide (Ti3C2Tx) MXene was used for electrode modification. 2D Ti3C2Tx could immobilize aptamers via chelation between titanium and phosphate groups and provide a large electroactive surface for signal transduction. Another 2D zirconium ferrocene-based metal–organic framework (Zr-Fc MOF) combined with gold nanoparticles (AuNPs) and 4-mercaptophenylboronic acid (4-MPBA) (Zr-Fc MOF/AuNPs/4-MPBA) was used as an electrochemical signal label, in which Fc was a signal molecule and AuNPs could improve the electroactivity and combine with 4-MPBA via Au–S bonds. 4-MPBA could bind with E. coli O157:H7 via covalent bonding between boronic acid and the cis-diol of lipopolysaccharides on bacteria cell walls. So, the signal labels could immobilize on the electrode to form a Faraday-cage-type structure owing to the large surface area of Zr-Fc MOF. In this structure, electrons flowed directly between the electrode and ferrocene, and the electrochemical signal could be amplified. When the application of 2D nanomaterials and the Faraday-cage strategy were combined, E. coli O157:H7 was sensitively detected with a detection limit of 3 CFU·mL–1. The aptasensor was applied for milk sample detection. This aptasensor has practical application potential because of its properties of satisfactory sensitivity, specificity, and stability. [ABSTRACT FROM AUTHOR]

In this study, a strength gradient is produced in Al-Cu-Ca alloy foam by aging treatment with a temperature gradient. The microscopic results show that the morphology and the amount of Al2Cu strengthening precipitates in the base alloy change with the local aging temperature. Graded microstructures in the base alloy are realized along with the temperature gradient, subsequently producing the strength gradient in the Al-Cu-Ca foam. Under compression, the lower strength portion of the foam sample firstly collapsed until complete densification and then extended to the higher strength portion, suggesting a notable strength gradient. The tailorable graded aging treatment provided a higher degree of freedom in designing and producing the strength gradient in aluminum foam. [ABSTRACT FROM AUTHOR]

The sensitive detection of biomarkers is crucial for the early identification and treatment of cancer. In this study, a cysteine–histidine–Cu-modified jujube-like Cu2O (CH-Cu@J-Cu2O) nanozyme was synthesized and used to fabricate an electrochemical sensor for mucin-1 (MUC1) sensitive detection. Gold-modified reduced graphene oxide and CH-Cu@J-Cu2O for the sensor were prepared and also characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The CH-Cu@J-Cu2O nanozyme was used as a signal probe, containing two catalytic units of cysteine–histidine–Cu and jujube-like Cu2O. The CH-Cu@J-Cu2O nanozyme can potently catalyze the H2O2-driven oxidation of dopamine to aminochrome, leading to a high-level electrochemical signal. This electrochemical sensor was used to detect MUC1 with a linear range from 0.5 to 5000 pg·mL–1, and the limit of detection was 0.085 pg·mL–1, owing to the excellent catalytic activity of CH-Cu@J-Cu2O. The expression of MUC1 on the surface of MCF-7 cells was further analyzed, and the results indicate that the proposed strategy is practical for the detection of biomarkers. [ABSTRACT FROM AUTHOR]

Nanozymes have enzyme-like characteristics and nanozyme-based electrochemical sensors have been widely studied for biomarker detection. In this work, cuprous oxide-modified reduced graphene oxide (Cu2O–rGO) nanozyme was prepared by simultaneous reduction of copper chloride and graphene oxide. This Cu2O–rGO nanozyme displayed an outstanding electrocatalytic activity to glucose oxidation and was used as the modified material of a glassy carbon electrode to fabricate an electrochemical ratiometric biosensor for glycated albumin (GA) detection. In this ratiometric biosensor, methylene blue-labeled DNA tripods (MB-tDNA) were adsorbed on the Cu2O–rGO/GCE surface to form a bioinspired electrode (MB-tDNA/Cu2O–rGO/GCE), in which the catalytic sites of Cu2O–rGO were covered by MB-tDNA. In the presence of target GA, GA could be identified by the aptamer sequence contained in MB-tDNA, and a MB-tDNA/GA complex was formed and released into the solution, so the reduced current of MB-tDNA was decreased. Simultaneously, the oxidized current of the outer added glucose was increased since more catalytic sites of Cu2O–rGO nanozyme on the substrate electrode surface were exposed. The ratio of the peak currents of glucose oxidation and methylene blue reduction (IGlu/IMB) was used to monitor the GA level and ultimately improve the accuracy of the method. The electrochemical sensor showed a low detection limit of 0.007 μg mL−1 and a wide linear range from 0.02 to 1500 μg mL−1. The proposed sensor was also successfully used to measure the GA expression level in the blood serum of a diabetic mouse model. [ABSTRACT FROM AUTHOR]

An electrochemical sensor based on dual functional Cu2+-modified metal–organic framework nanoparticles (Cu2+-NMOFs) for sensitive detection of bacterial lipopolysaccharide (LPS) is reported. Cu2+-NMOFs were prepared and characterized by SEM, EDS, XRD, and XPS. In this LPS sensor, LPS firstly immobilized in gold nanoparticles/reduced graphene oxide by C18 alkane thiol chains, since the LPS can interact with the C18 alkyl chains by strong intermolecular interactions. Then the Cu2+-NMOFs were captured by the anionic groups of the carbohydrate portions of LPS molecules and played a vital role of recognition unit. More importantly, the Cu2+-NMOFs can catalyze dopamine oxidation to generate aminochrome, resulting in a strong electrochemical oxidation signal. The electrochemical sensor based on dual functional Cu2+-NMOFs was investigated by differential pulse voltammetry, and the stripping peak currents of dopamine oxidized to aminochrome were used to monitor the level of LPS. The developed method demonstrated a wide linear range from 0.0015 to 750 ng/mL with a limit of detection of 6.1 × 10−4 ng/mL. The fabricated sensor was applied to detect LPS in mouse blood serum and satisfactory results were achieved. Compared to other detection schemes by using the LPS-binding proteins, peptides, and aptamer, the proposed LPS determination based on the catalytic peroxidase-mimicking NMOFs has some advantages such as good reproducibility, low detection limit, and excellent specificity. [ABSTRACT FROM AUTHOR]

Biochemical and electrophysiological methods are used to investigate the role of the high-conductance calcium-activated potassium (Maxi-K) channel C-terminal domain in channel tetramerization. The results indicate that the channel domain ranging from the N-terminus through the S6 linker region contains the determinants necessary for formation and surface expression of tetramers.

Research reveals that substitution of lysine22 with a diaminopropionic acid residue in Stichodactyla helianthus venom ShK peptide, ShK-Dap22, changes the in vivo immunosuppressant efficacy of other potassium channel blockers. Furthermore, from a pharmacological point of view ShK-Dap22 may cause side effects due to its interaction with other blockers.

Insulin-induced hypoglycemia in diabetes is associated with impaired glucagon secretion. In this study, we tested whether stimulation of GPR119, a G-protein-coupled receptor expressed in pancreatic islet as well as enteroendocrine cells and previously shown to stimulate insulin and incretin secretion, might enhance glucagon secretion during hypoglycemia. In the study, GPR119 agonists were applied to isolated islets or perfused pancreata to assess insulin and glucagon secretion during hypoglycemic or hyperglycemic conditions. Insulin infusion hypoglycemic clamps were performed with or without GPR119 agonist pretreatment to assess glucagon counterregulation in healthy and streptozotocin (STZ)-induced diabetic rats, including those exposed to recurrent bouts of insulin-induced hypoglycemia that leads to suppression of hypoglycemia-induced glucagon release. Hypoglycemic clamp studies were also conducted in GPR119 knockout (KO) mice to evaluate whether the pharmacological stimulatory actions of GPR119 agonists on glucagon secretion during hypoglycemia were an on-target effect. The results revealed that GPR119 agonist-treated pancreata or cultured islets had increased glucagon secretion during low glucose perfusion. In vivo, GPR119 agonists also significantly increased glucagon secretion during hypoglycemia in healthy and STZ-diabetic rats, a response that was absent in GPR119 KO mice. In addition, impaired glucagon counterregulatory responses were restored by a GPR119 agonist in STZ-diabetic rats that were exposed to antecedent bouts of hypoglycemia. Thus, GPR119 agonists have the ability to pharmacologically augment glucagon secretion, specifically in response to hypoglycemia in diabetic rodents. Whether this effect might serve to diminish the occurrence and severity of iatrogenic hypoglycemia during intensive insulin therapy in patients with diabetes remains to be established. [ABSTRACT FROM AUTHOR]

The nano to submicro-porous β-titanium molybdenum (TiMo) foams are prepared by dealloying of (TiMo)1-xCux master alloys using a solid state dealloying method. The dealloying is performed within Mg powders by a pressureless spark plasma sintering (SPS). Experimental results show that Cu atoms in the master alloy are selectively dissolved into Mg powders during heating, the Ti and Mo atoms are spontaneously organized into homogeneous open-cell β-TiMo foams. The foams from (Ti15Mo)40Cu60 alloy have BET surface area of 28.96 m2 g-1 and pore sizes mostly in the range of 3.42 to 50 nm. The hardness and elastic modulus of the foams decrease dramatically with nanoporosities from 55.1 to 74.2%. Solid state dealloying by using pressureless SPS is promising for developing functional nanoporous (NP) Ti alloy foams. [ABSTRACT FROM AUTHOR]

Insulin resistance is the key feature of type 2 diabetes and is manifested as attenuated insulin receptor (IR) signaling in response to same levels of insulin binding. Several small molecule IR activators have been identified and reported to exhibit insulin sensitization properties. One of these molecules, TLK19781 (Cmpd1), was investigated to examine its IR sensitizing action in vivo. Our data demonstrate that Cmpd1, at doses that produced minimal efficacy in the absence of insulin, potentiated insulin action during an OGTT in non-diabetic mice and enhanced insulin-mediated glucose lowering in diabetic mice. Interestingly, different from insulin alone, Cmpd1 combined with insulin showed enhanced efficacy and duration of action without increased hypoglycemia. To explore the mechanism underlying the apparent glucose dependent efficacy, tissue insulin signaling was compared in healthy and diabetic mice. Cmpd1 enhanced insulin’s effects on IR phosphorylation in both healthy and diabetic mice. In contrast, the compound potentiated insulin’s effects on Akt phosphorylation in diabetic but not in non-diabetic mice. These differential effects on signaling corresponding to glucose levels could be part of the mechanism for reduced hypoglycemia risk. The in vivo efficacy of Cmpd1 is specific and dependent on IR expression. Results from these studies support the idea of targeting IR for insulin sensitization, which carries low hypoglycemia risk by standalone treatment and could improve the effectiveness of insulin therapies. [ABSTRACT FROM AUTHOR]

• HSP70 expression was induced by TMUV infection. • HSP70 inhibitor blocks TMUV infection. • TMUV cycle requires HSP70 for RNA replication, viron assembly and release. • HSP70 was found associated with TMUV particles. Tembusu virus (TMUV) is an avian-origined flavivirus that is prevalent in ducks and geese. TMUV causes reduced egg production and neurological problems, resulting in profound economic losses to the waterfowl industry. In the viral life cycle, cellular factors are required for viral entry, replication, assembly, release and so on. Heat shock protein 70 (HSP70) is reported to be involved in the replication of multiple viruses. In this study, we explored the roles of HSP70 in the TMUV life cycle. The results showed that TMUV infection induced HSP70 expression starting 12 h post-infection. An HSP70 inhibitor reduced TMUV viral RNA production and the number of virus particles, whereas an HSP70 activator enhanced the amount of viral RNA and virions that released from the cells. Further analysis revealed that HSP70 played important roles in the postentry stages of the TMUV life cycle, including viral replication, assembly and release. We also found that inhibition of HSP70 expression significantly reduced TMUV-induced apoptosis. Additionally, incubation of TMUV particles with an anti-HSP70 antibody significantly reduced viral infectivity, suggesting an association between HSP70 and TMUV particles. These results implicate HSP70 in the life cycle of TMUV, and therefore, targeting HSP70 may be a strategy for developing an anti-TMUV therapy. [ABSTRACT FROM AUTHOR]