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Metabolism-based solutions for epilepsy: new instructions pertaining to upcoming cures.
Recently, our group introduced the use of silver nanowires (AgNWs) as novel non-invasive endoscopic probes for detecting intracellular Raman signals. This method, although innovative and promising, relies exclusively on the plasmonic waveguiding effect for signal enhancement. It, therefore, requires sophisticated operational tools and protocols, drastically limiting its applicability. Herein, an advanced strategy is offered to significantly enhance the performance of these endoscopic probes, making this approach widely accessible and versatile for cellular studies. By uniformly forming gold structures on the smooth AgNW surface via a galvanic replacement reaction, the density of the light coupling points along the whole probe surface is drastically increased, enabling high surface-enhanced Raman scattering (SERS) efficiency upon solely focusing the excitation light on the gold-etched AgNW. The applicability of these gold-etched AgNW probes for molecular sensing in cells is demonstrated by detecting site-specific and high-resolved SERS spectra of cell compartment-labeling dyes, namely, 4',6-diamidino-2-phenylindole in the nucleus and 3,3'-dioctadecyloxacarbocyanine on the membrane. The remarkable spectral sensitivity achieved provides essential structural information of the analytes, indicating the overall potential of the proposed approach for cellular studies of drug interactions with biomolecular items.ZnT8 is a human zinc(II) transporter expressed at the membrane of secretory granules where it contributes to insulin storage importing zinc ions from the cytosol. In the human population, the two most common ZnT8 variants carry an arginine (R325) or a tryptophan (W325) in position 325. The former variant has the most efficient kinetics in zinc transport and has been correlated to a higher risk of developing insulin resistance. On the contrary, the W325 variant is less active and protects against type-2-diabetes. Here, we used molecular dynamics (MD) simulations to investigate the main differences between the R325 and W325 variants in the interaction with zinc(II) ions. Our simulations suggested that the position of the metal ion within the transport site was not the same for the two variants, underlying a different rearrangement of the transmembrane (TM) helices in the channel. The W325 variant featured a peculiar zinc environment not detected in the experimental structures. With respect to conformational dynamics, we observed that the R325 variant was significantly more flexible than W325, with the main role played by the transmembrane domain (TMD) and the C-terminal domain (CTD). This dynamics affected the packing of the TM helices and thus the channel accessibility from the cytosol. find more The dimer interface that keeps the two TM channels in contact became looser in both variants upon zinc binding to the transport site, suggesting that this may be an important step toward the switch from the inward- to the outward-facing state of the protein.Total redox capacity (TRC) and oxidative stress (OxiStress) of biological objects (such as cells, tissues, and body fluids) are some of the most frequently analyzed parameters in life science. Development of highly sensitive molecular probes and analytical methods for detection of these parameters is a rapidly growing sector of BioTech's R&D industry. The aim of the present study was to develop quantum sensors for tracking the TRC and/or OxiStress in living biological objects using electron-paramagnetic resonance (EPR), magnetic resonance imaging (MRI), and optical imaging. We describe a two-set sensor system (i) TRC sensor QD@CD-TEMPO and (ii) OxiStress sensor QD@CD-TEMPOH. Both redox sensors are composed of small-size quantum dots (QDs), coated with multinitroxide-functionalized cyclodextrin (paramagnetic CD-TEMPO or diamagnetic CD-TEMPOH) conjugated with triphenylphosphonium (TPP) groups. The TPP groups were added to achieve intracellular delivery and mitochondrial localization. Nitroxide residues interact simultaneously with various oxidizers and reducers, and the sensors are transformed from the paramagnetic radical form (QD@CD-TEMPO) into diamagnetic hydroxylamine form (QD@CD-TEMPOH) and vice-versa, because of nitroxide redox-cycling. These chemical transformations are accompanied by characteristic dynamics of their contrast features because of quenching of QD fluorescence by nitroxide radicals. The TRC sensor was applied for EPR analysis of cellular redox-status in vitro on isolated cells with different proliferative indexes, as well as for noninvasive MRI of redox imbalance and severe oxidative stress in vivo on mice with renal dysfunction.Residential energy demand can be greatly influenced by the types of housing structures that households live in, but few studies have assessed changes in the composition of housing stocks as a strategy for reducing residential energy demand or greenhouse gas (GHG) emissions. In this paper we examine the effects of three sequenced federal policies on the share of new housing construction by type in the U.S., and estimate the cumulative influence of those policies on the composition of the 2015 housing stock. In a counterfactual 2015 housing stock without the policy effects, 14 million housing units exist as multifamily rather than single-family, equal to 14.1% of urban housing. Accompanied by floor area reductions of 0-50%, the switch from single- to multifamily housing reduces energy demand by 27-47% per household, and total urban residential energy by 4.6-8.3%. This paper is the first to link federal policies to housing outcomes by type and estimate associated effects on residential energy and GHG emissions. Removing policy barriers and disincentives to multifamily housing can unlock a large potential for reducing residential energy demand and GHG emissions in the coming decades.Separation of uranium and cesium from low-level radioactive effluents (LLRE) is of great significance for sustainable development of the nuclear industry and for the environment. However, high salinity and massive coexisting ions of LLRE are giant challenges for the separation. To address the challenges, we report a strategy for efficient and simultaneous separation of uranium and cesium from a high-salt environment by dual ion-imprinted mesoporous silica based on multiple interactions. The as-prepared adsorbents can reach equilibrium for uranium and cesium within 1 h with a maximum capacity of 221.7 mg U g-1 and 34.5 mg Cs g-1. The sorption mechanism demonstrates that the highly active phenolic hydroxyl groups of imprinted cavities can extract uranium and cesium effectively through multiple interactions, including coulomb attraction, redox, ion exchange, and complexation. The synergism of multiple interactions and imprinted cavity endows the sorbent with good selectivity for uranium and cesium over other cations and with excellent salt tolerance.
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