A class of zinc reagents (RXZnCH(2)Y) generated with an appropriate organozinc is very effective for the cyclopropanation of olefins. The reactivity and selectivity of these reagents can be regulated by tuning the electronic and steric nature of the RX group on Zn. A reasonable level of enantioselectivity was obtained for the cyclopropanation of unfunctionalized olefins when a chiral (iodomethyl)zinc species was used, providing a valuable approach for the asymmetric cyclopropanation of unfunctionalized olefins.

We establish an adaptive batch-normalized neural network, aiming to implement smart and rapid inverse design for graphene-based metamaterials with on-demand optical responses.

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Liver X Receptors (LXRs) a and b are nuclear hormone receptors that regulate multiple genes involved in reverse cholesterol transport (RCT) and are potential drug targets for atherosclerosis. However, full pan agonists also activate lipogenic genes, resulting in elevated plasma and hepatic lipids. We report the pharmacol-a potent partial LXR agonist with LXRb selectivity, which has an improved therapeutic window in the cynomolgus monkey compared with a full pan agonist. BMS-779788 induced LXR target genes in blood in vivo with an EC 50 5 610 nM, a value similar to its in vitro blood gene induction potency. BMS-779788 was 29-and 12-fold less potent than the full agonist T0901317 in elevating plasma triglyceride and LDL cholesterol, respectively, with similar results for plasma cholesteryl ester transfer protein and apolipoprotein B. However, ABCA1 and ABCG1 mRNA inductions in blood, which are critical for RCT, were comparable. Increased liver triglyceride was observed after 7-day treatment with BMS-779788 at the highest dose tested and was nearly identical to the dose response for plasma triglyceride, consistent with the central role of liver LXR in these lipogenic effects. Dose-dependent increases in biliary cholesterol and decreases in phospholipid and bile acid occurred in BMS-779788-treated animals, similar to LXR agonist effects reported in mouse. In summary, BMS-779788, a partial LXRb selective agonist, has decreased lipogenic potential compared with a full pan agonist in cynomolgus monkeys, with similar potency in the induction of genes known to stimulate RCT. This provides support in nonhuman primates for improving LXR agonist therapeutic windows by limiting LXRa activity.

Terahertz (THz) sensing of molecular fingerprint enables wide applications in biomedicine and security detection. Conventional detection approaches face big barriers in trace analysis of analyte due to the difficulties of enhancing the broadband molecular absorption. In order to achieve strong broadband wave–matter interaction for the analyte, we propose a method based on THz wave angular scanning on a dielectric metagrating. In virtue of the guided-mode resonance, one can strengthen the local electric field in various trace-amount analytes by tuning the polarization and incident angle, which leads to significant enhancement on the broadband signal of molecular fingerprint. The study paves the way for more applications of THz trace-amount detection.

Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist . The addition of polarity to the phenyl sulfone also reduced binding to the plasma protein, human α-1-acid glycoprotein. Agonist was selected for clinical development based on the favorable combination of properties, excellent pharmacokinetic parameters, and a favorable lipid profile.

Optical biosensors are a versatile detection and analysis tool used in biological research, health care, pharmaceuticals, environmental monitoring, homeland security, and the battlefield. [1] They do not interfere with electromagnetic (EM) radiation, manifest distant sensing capability, and may enable multiplexed detection in a single device. Optical biosensing technologies are widely used in current biomedical and environmental monitoring applications because they provide a reliable and quick way to identify and discriminate specific objects from a wide range of samples. [2][3][4][5] More interestingly, Optical biosensors outperform standard analytical techniques by delivering highly-sensitive, selective, and cost-effective real-time and label-free detection of biological and chemical molecules. [6,7] High specificities, sensitivity, small size, and cost-effectiveness are among the benefits.Metasurfaces are planar or 2D forms of metamaterials made up of arrays of antennas with a subwavelength thickness. They have been rapidly developed in the recent years due to their ability to manipulate light-matter interaction in both linear and non-linear regimes at the nanoscale. Various metasurfaces display remarkable optical features, such as acute resonance, significant nearfield enhancement, and suitable capacity to support electric and magnetic modes, on account of the strong light-matter interaction and the low optical loss. Due to these important properties, they can be used in several advanced optoelectronic applications, like surface-enhanced spectroscopy, photocatalysis, and sensing. This review reports on the recent progress of metamaterials and metasurfaces in molecular optical sensors. The principles that govern plasmonic and dielectric metasurfaces along with their features are outlined, supported by numerous examples. Then, the factors that result in a high Q-factor are presented in order to show that metamaterials and metasurfaces can be used for label-free sensing in a variety of detection mechanisms, including surface-enhanced spectroscopy, refractometric sensing, and surface-enhanced thermal emission spectroscopy via infrared absorption and Raman scattering, as well as chiral sensing. Finally, the challenges for future development are outlined.

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