Role of Aluminum and Lithium in Mitigating Alkali-Silica Reaction—A Review

Effective mitigation of alkali-silica reaction (ASR) is critical for producing durable concrete. The use of alumina-rich supplementary cementitious materials (SCMs) and chemical admixtures such as lithium salts to prevent expansion caused by ASR was first reported 70 years ago, shortly after the discovery of ASR in 1940s. Despite numerous investigations, the understanding of the mechanisms of Al and Li for mitigating ASR remain partially inexplicit in the case of Al, and hardly understood in the case of Li. This paper reviews the available information on the effect of Al and Li on ASR expansion, the influencing factors, possible mechanisms and limitations. The role of Al in mitigating ASR is likely related to the reduction of dissolution rate of reactive silica. Moreover, the presence of Al may alter the structure of crystalline ASR products to zeolite or its precursor, but such effect seems to be not that significant at ambient conditions due to the slow kinetics of zeolite formation. Several mechanisms for the lithium salts in mitigating ASR have been proposed, but most of them are not conclusive primarily due to the lack of knowledge about the formed reaction products. Combination of Al-rich SCMs and lithium salts may be used as an economic solution for ASR mitigation, although systematic studies are necessary prior to the applications.

Lacosamide Inhibition of NaV1.7 Channels Depends on its Interaction With the Voltage Sensor Domain and the Channel Pore

Lacosamide, developed as an anti-epileptic drug, has been used for the treatment of pain. Unlike typical anticonvulsants and local anesthetics which enhance fast-inactivation and bind within the pore of sodium channels, lacosamide enhances slow-inactivation of these channels, suggesting different binding mechanisms and mode of action. It has been reported that lacosamide’s effect on NaV1.5 is sensitive to a mutation in the local anesthetic binding site, and that it binds with slow kinetics to the fast-inactivated state of NaV1.7. We recently showed that the NaV1.7-W1538R mutation in the voltage-sensing domain 4 completely abolishes NaV1.7 inhibition by clinically-achievable concentration of lacosamide. Our molecular docking analysis suggests a role for W1538 and pore residues as high affinity binding sites for lacosamide. Aryl sulfonamide sodium channel blockers are also sensitive to substitutions of the W1538 residue but not of pore residues. To elucidate the mechanism by which lacosamide exerts its effects, we used voltage-clamp recordings and show that lacosamide requires an intact local anesthetic binding site to inhibit NaV1.7 channels. Additionally, the W1538R mutation does not abrogate local anesthetic lidocaine-induced blockade. We also show that the naturally occurring arginine in NaV1.3 (NaV1.3-R1560), which corresponds to NaV1.7-W1538R, is not sufficient to explain the resistance of NaV1.3 to clinically-relevant concentrations of lacosamide. However, the NaV1.7-W1538R mutation conferred sensitivity to the NaV1.3-selective aryl-sulfonamide blocker ICA-121431. Together, the W1538 residue and an intact local anesthetic site are required for lacosamide’s block of NaV1.7 at a clinically-achievable concentration. Moreover, the contribution of W1538 to lacosamide inhibitory effects appears to be isoform-specific.

Optogenetic Stimulation of Gi Signaling Enables Instantaneous Modulation of Cardiomyocyte Pacemaking

G-protein signaling pathways are central in the regulation of cardiac function in physiological and pathophysiological conditions. Their functional analysis through optogenetic techniques with selective expression of opsin proteins and activation by specific wavelengths allows high spatial and temporal precision. Here, we present the application of long wavelength-sensitive cone opsin (LWO) in cardiomyocytes for activation of the Gi signaling pathway by red light. Murine embryonic stem (ES) cells expressing LWO were generated and differentiated into beating cardiomyocytes in embryoid bodies (EBs). Illumination with red light (625 nm) led to an instantaneous decrease up to complete inhibition (84–99% effectivity) of spontaneous beating, but had no effect on control EBs. By using increasing light intensities with 10 s pulses, we determined a half maximal effective light intensity of 2.4 μW/mm2 and a maximum effect at 100 μW/mm2. Pre-incubation of LWO EBs with pertussis toxin completely inhibited the light effect proving the specificity for Gi signaling. Frequency reduction was mainly due to the activation of GIRK channels because the specific channel blocker tertiapin reduced the light effect by ~80%. Compared with pharmacological stimulation of M2 receptors with carbachol with slow kinetics (>30 s), illumination of LWO had an identical efficacy, but much faster kinetics (<1 s) in the activation and deactivation demonstrating the temporal advantage of optogenetic stimulation. Thus, LWO is an effective optogenetic tool for selective stimulation of the Gi signaling cascade in cardiomyocytes with red light, providing high temporal precision.

N, S, P-Codoped Graphene-Supported Ag-MnFe2O4 Heterojunction Nanoparticles as Bifunctional Oxygen Electrocatalyst with High Efficiency

Due to slow kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) during discharging and charging processes, it is essential to rationally design and synthesize non-precious metal bifunctional electrocatalysts with good performance for metal-air batteries. Herein, Ag-MnFe2O4 heterojunction nanoparticles supported on N, S, P-codoped graphene (NSPG) are developed with enhanced ORR and OER bifunctional electrocatalytic activities and stability. In contrast, S, P-doped graphene (SPG) and N, P-doped graphene (NPG) show less stabilization for the heterojunction particles. For example, under alkaline conditions, the ORR half-wave potential of Ag-MnFe2O4/NSPG can reach 0.831 V, and the over potential for OER is 0.56 V at the current density 10 mA·cm−2. Furthermore, Ag-MnFe2O4/NSPG shows better methanol resistance and durability than Pt/C catalysts.

Evaluation of borinic acids as new, fast hydrogen peroxide–responsive triggers

Hydrogen peroxide (H2O2) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of H2O2-mediated signaling in physiological and pathological processes. For this purpose, various “off–on” small fluorescent probes relying on a boronate trigger have been prepared, and this design has also been involved in the development of H2O2-activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by H2O2 with a short response time. Therefore, faster H2O2-reactive groups are awaited. To address this issue, we have successfully developed and characterized a prototypic borinic-based fluorescent probe containing a coumarin scaffold. We determined its in vitro kinetic constants toward H2O2-promoted oxidation. We measured 1.9 × 104m−1⋅s−1 as a second-order rate constant, which is 10,000-fold faster than its well-established boronic counterpart (1.8 m−1⋅s−1). This improved reactivity was also effective in a cellular context, rendering borinic acids an advantageous trigger for H2O2-mediated release of effectors such as fluorescent moieties.

Lignin-Assisted Water Electrolysis for Energy-Saving Hydrogen Production With Ti/PbO2 as the Anode

Replacing the oxygen evolution reaction (OER), which is of high energy consumption and slow kinetics, with the more thermodynamically favorable reaction at the anode can reduce the electricity consumption for hydrogen production. Here we developed a lignin-assisted water electrolysis (LAWE) process by using Ti/PbO2 with high OER overpotential as the anode aimed at decreasing the energy consumption for hydrogen production. The influence of key operating parameters such as temperature and lignin concentration on hydrogen production was analyzed. Compared with alkaline water electrolysis (AWE), the anode potential can be decreased from 0.773 to 0.303 (V vs. Hg/HgO) at 10 mA/cm2 in LAWE, and the corresponding cell voltage can be reduced by 546 mV. With increasing the temperature and lignin concentration, current density and H2 production rate were efficiently promoted. Furthermore, the anode deactivation was investigated by analyzing the linear sweep voltammetry (LSV) and cyclic voltammetry (CV) tests. Results showed that the anode deactivation was affected by the temperature.

Ca2+/CaM binding to CaMKI promotes IMA-3 importin binding and nuclear translocation in sensory neurons to control behavioral adaptation

Sensory and behavioral plasticity are essential for animals to thrive in changing environments. As key effectors of intracellular calcium signaling, Ca2+/Calmodulin-dependent protein kinases (CaMKs) can bridge neural activation with the many regulatory processes needed to orchestrate sensory adaptation, including by relaying signals to the nucleus. Here, we elucidate the molecular mechanism controlling the cell activation-dependent nuclear translocation of CMK-1, the C. elegans ortholog of mammalian CaMKI/IV, in thermosensory neurons in vivo. We show that an intracellular Ca2+ concentration elevation is necessary and sufficient to favor CMK-1 nuclear import. The binding of Ca2+/CaM to CMK-1 increases its affinity for IMA-3 importin, causing a redistribution with a relatively slow kinetics, matching the timescale of sensory adaptation. Furthermore, we show that this mechanism enables the encoding of opposite nuclear signals in neuron types with opposite calcium-responses and that it is essential for experience-dependent behavioral plasticity and gene transcription control in vivo. Since CaMKI/IV are conserved regulators of adaptable behaviors, similar mechanisms could exist in other organisms and for other sensory modalities.

Surface Enhanced Infrared Spectroelectrochemistry using a Microband Electrode

The successful use of a microband electrode printed on a silicon internal reflection element to perform time resolved infrared spectroscopy is described. Decreasing the critical dimension of the microband electrode to several hundred micrometers provides a sub-microsecond time constant in a Kretschmann configured spectroelectrochemical cell. The high brilliance of synchrotron sourced infrared radiation has been combined with a specially designed horizontal attenuated total reflectance (ATR) microscope to focus the infrared beam on the microband electrode. The first use of a sub-microsecond time constant working electrode for ATR surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) is reported. Measurements show that the advantage afforded by the high brilliance of the synchrotron source is at least partially offset by increased noise from the experimental floor. The test system was the potential induced desorption of an adsorbed monolayer of 4-methoxypyridine as measured using step-scan interferometry. Based on diffusion considerations alone, the expected time scale of the process was less than 10 microseconds but was experimentally measured to be three orders of magnitude slower. A defect-mediated dissolution of the condensed film is speculated to be the underlying cause of the unexpected slow kinetics.

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinib-treated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose.

Marginal defects modified graphene with S-C-N-C groups for highly selective oxygen reduction to H2O2

Developing efficient metal-free catalysts to achieve electrochemical synthesis of hydrogen peroxide (H2O2) is crucial for substituting traditional energy-intensive anthraquinone process. Heteroatom-doped carbon materials have shown great potential toward 2e-pathway for catalyzing oxygen reduction to hydrogen peroxide (ORHP). However, conventional nanocarbon electrocatalysts show slow kinetics toward ORHP due to the weak binding strength with OOH* intermediate, resulting reduction of O2 to H2O. Here, sulfur and nitrogen dual-doped graphene (SNC) electrocatalyst consisting of S-C-N-C functional group are synthesized through hydrothermal self-assembly and nitridation processes with thiourea as sulfur source. In S-C-N-C functional group, pentagon-S and pyrrolic-N are covalently grafted onto the edge of graphene and produce marginal carbon ring defects, which provide highly active sites for catalyzing ORHP. The obtained SNC catalysts deliver an outstanding ORHP activity and selectivity for H2O2 production, while retaining remarkable stability. The experimental and computational results reveal that marginal S-C-N-C functional groups afford an appropriate adsorption strength with OOH* intermediate and a low reaction barrier as well, which are essential for the activity of ORHP.