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Molecular chirality is represented as broken mirror symmetry in the structural orientation of constituent atoms and plays a pivotal role at every scale of nature. Since the discovery of the chiroptic property of chiral molecules, the characterization of molecular chirality is important in the fields of biology, physics, and chemistry. Over the centuries, the field of optical chiral sensing was based on chiral light–matter interactions between chiral molecules and polarized light. Starting from simple optics-based sensing, the utilization of plasmonic materials that could control local chiral light–matter interactions by squeezing light into molecules successfully facilitated chiral sensing into noninvasive, ultrasensitive, and accurate detection. In this Review, the importance of plasmonic materials and their engineering in chiral sensing are discussed based on the principle of chiral light–matter interactions and the theory of optical chirality and chiral perturbation; thus, this Review can serve as a milestone for the proper design and utilization of plasmonic nanostructures for improved chiral sensing. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is an increasing global health crisis, affecting 40 million people and causing 50% mortality within 5 years of diagnosis. A fuller understanding of the genetic and environmental factors underlying HF, and novel therapeutic approaches to address it, are urgently warranted. Here, we discovered that cardiac-specific germline deletion in mice of potassium channel β subunit-encoding Kcne2 (Kcne2CS-/- ) causes dilated cardiomyopathy and terminal HF (median longevity, 28 weeks). Mice with global Kcne2 deletion (Kcne2Glo-/- ) exhibit multiple HF risk factors, yet, paradoxically survived over twice as long as Kcne2CS-/- mice. Global Kcne2 deletion, which inhibits gastric acid secretion, reduced the relative abundance of species within Bacteroidales, a bacterial order that positively correlates with increased lifetime risk of human cardiovascular disease. Strikingly, the proton-pump inhibitor omeprazole similarly altered the microbiome and delayed terminal HF in Kcne2CS-/- mice, increasing survival 10-fold at 44 weeks. Thus, genetic or pharmacologic induction of hypochlorhydria and decreased gut Bacteroidales species are associated with lifespan extension in a novel HF model.

Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM. Kcne2 deletion also caused extensive pancreatic transcriptome changes consistent with facets of T2DM, including endoplasmic reticulum stress, inflammation, and hyperproliferation. Kcne2 deletion impaired β-cell insulin secretion in vitro up to 8-fold and diminished β-cell peak outward K+ current at positive membrane potentials, but also left-shifted its voltage dependence and slowed inactivation. Interestingly, we also observed an aging-dependent reduction in β-cell outward currents in both Kcne2+/+ and Kcne2-/- mice. Our results demonstrate that KCNE2 is required for normal β-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM. KCNE2 may regulate multiple K+ channels in β cells, including the T2DM-linked KCNQ1 potassium channel α subunit.-Lee, S. M., Baik, J., Nguyen, D., Nguyen, V., Liu, S., Hu, Z., Abbott, G. W. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.

Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2(─/─) mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis.

Coronary artery disease (CAD) is the leading cause of death worldwide. An estimated half of cases involve genetic predisposition. Sequence variants in human KCNE2, which encodes a cardiac and epithelial K(+) channel β subunit, cause inherited cardiac arrhythmias. Unexpectedly, human KCNE2 polymorphisms also associate with predisposition to atherosclerosis, with unestablished causality or mechanisms. Here, we report that germline Kcne2 deletion promotes atherosclerosis in mice, overcoming the relative resistance of this species to plaque deposition. In female western diet-fed mice, Kcne2 deletion increased plaque deposition >6-fold and also caused premature ventricular complexes and sudden death. The data establish causality for the first example of ion channel-linked atherosclerosis, and demonstrate that the severity of Kcne2-linked cardiac arrhythmias is strongly diet-dependent.