Ketone bodies supplementation restores the barrier function, induces a metabolic switch, and elicits beta-hydroxybutyrate diffusion across a monolayer of iPSC-derived brain microvascular endothelial cells.

Glucose constitutes the main source of energy for the central nervous system (CNS), its entry occurring at the blood-brain barrier (BBB) via the presence of glucose transporter 1 (GLUT1). However, under food intake restrictions, the CNS can utilize ketone bodies (KB) as an alternative source of energy. Notably, the relationship between the BBB and KBs and its effect on their glucose metabolism remains poorly understood. In this study, we investigated the effect of glucose deprivation on the brain endothelium in vitro, and supplementation with KBs using induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cell-like cells (iBMECs). Glucose-free environment significantly decreased cell metabolic activity and negatively impacted the barrier function. In addition, glucose deprivation did not increase GLUT1 expression but also resulted in a decrease in glucose uptake and glycolysis. Supplementation of glucose-deprived iBMECs monolayers with KB showed no improvement and even worsened upon treatment with acetoacetate. However, under a hypoglycemic condition in the presence of KBs, we noted a slight improvement of the barrier function, with no changes in glucose uptake. Notably, hypoglycemia and/or KB pre-treatment elicited a saturable beta-hydroxybutyrate diffusion across iBMECs monolayers, such diffusion occurred partially via an MCT1-dependent mechanism. Taken together, our study highlights the importance of glucose metabolism and the reliance of the brain endothelium on glucose and glycolysis for its function, such dependence is unlikely to be covered by KBs supplementation. In addition, KB diffusion at the BBB appeared induced by KB pre-treatment and appears to involve an MCT1-dependent mechanism.

Metal-Halide Perovskite Lasers: Cavity Formation and Emission Characteristics.

Hybrid metal-halide perovskites (MHPs) have shown remarkable optoelectronic properties as well as facile and cost-effective processability. With the success of MHP solar cells and light-emitting diodes, MHPs have also exhibited great potential as gain media for on-chip lasers. However, to date, stable operation of optically pumped MHP lasers and electrically driven MHP lasers-an essential requirement for MHP laser's insertion into chip-scale photonic integrated circuits-is not yet demonstrated. The main obstacles include the instability of MHPs in the atmosphere, rudimentary MHP laser cavity patterning methods, and insufficient understanding of emission mechanisms in MHP materials and cavities. This review aims to provide a detailed overview of different strategies to improve the intrinsic properties of MHPs in the atmosphere and to establish an optimal MHP cavity patterning method. In addition, this review discusses different emission mechanisms in MHP materials and cavities and how to distinguish them.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR.

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing-based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.

"ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells.

The regulation of cyclic adenosine monophosphate (cAMP) levels in kidney epithelial cells is important in at least 2 groups of disorders, namely water balance disorders and autosomal dominant polycystic kidney disease. Focusing on the latter, we review genes that code for proteins that are determinants of cAMP levels in cells. We identify which of these determinants are expressed in the 14 kidney tubule segments using recently published RNA-sequencing and protein mass spectrometry data ("autosomal dominant polycystic kidney disease-omics"). This includes G protein-coupled receptors, adenylyl cyclases, cyclic nucleotide phosphodiesterases, cAMP transporters, cAMP-binding proteins, regulator of G protein-signaling proteins, G protein-coupled receptor kinases, arrestins, calcium transporters, and calcium-binding proteins. In addition, compartmentalized cAMP signaling in the primary cilium is discussed, and a specialized database of the proteome of the primary cilium of cultured "IMCD3" cells is provided as an online resource (https://esbl.nhlbi.nih.gov/Databases/CiliumProteome/). Overall, this article provides a general resource in the form of a curated list of proteins likely to play roles in determination of cAMP levels in kidney epithelial cells and, therefore, likely to be determinants of progression of autosomal dominant polycystic kidney disease.

Relationship Between Atopic Dermatitis and Food Allergy in Children.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by a compromised skin barrier due to a variety of reasons, such as hereditary predisposition, immunological overactivity, and skin microbiome disruption. There is strong evidence linking food allergies (FA) with AD in some children, and many children with AD develop asymptomatic food sensitivity. FA and AD are two frequent childhood illnesses that are closely related. Food allergies affect 30% of kids suffering from moderate and severe eczema and can cause a variety of symptoms, including dry, cracked skin, rash, itchiness, oozing, and crusted skin. While preteens and teens with AD are commonly sensitive to environmental allergens including house dust mites, mold, pollen, or dander of animals, younger kids with AD typically exhibit sensitivity to food items like peanuts, milk, or eggs. A food challenge test (FC) should be used to confirm allergies before recommending a stringent diet that could be hazardous to the patient. While elimination diets continue to be the cornerstone of the management of FA, they should only be carried out under the guidance of a specialist. Topical treatments are crucial for all individuals with AD. Early skin care with emollients, topical steroid treatment, and early introduction of highly allergenic foods are promising methods of alleviating symptoms of AD.

Directional Polarized Light Emission from Thin-Film Light-Emitting Diodes.

Light-emitting diodes (LEDs) with directional and polarized light emission have many photonic applications, and beam shaping of these devices is fundamentally challenging because they are Lambertian light sources. In this work, using organic and perovskite LEDs (PeLEDs) for demonstrations, by selectively diffracting the transverse electric (TE) waveguide mode while suppressing other optical modes in a nanostructured LED, the authors first demonstrate highly directional light emission from a full-area organic LED with a small divergence angle less than 3° and a TE to transverse magnetic (TM) polarization extinction ratio of 13. The highly selective diffraction of only the TE waveguide mode is possible due to the planarization of the device stack by thermal evaporation and solution processing. Using this strategy, directional and polarized emission from a perovskite LED having a current efficiency 2.6 times compared to the reference planar device is further demonstrated. This large enhancement in efficiency in the PeLED is attributed to a larger contribution from the TE waveguide mode resulting from the high refractive index in perovskite materials.

Recovering cavity effects in corrugated organic light emitting diodes.

Cavity effects play an important role in determining the out-coupling efficiency of an OLED. By fabricating OLEDs on corrugated substrates, the waveguide and SPP modes can be extracted by diffraction. However, corrugation does not always lead to an enhancement in out-coupling efficiency due to the reduction of the electrode reflectance and hence the cavity effects. Based on the results of our rigorous couple-wave analysis (RCWA) simulation, we found that the cavity effects can be partially recovered using a low index Teflon layer inserted between the ITO anode and the substrate due to the enhancement of the reflectance of the corrugated electrodes. To verify the simulation results, we fabricated corrugated OLEDs having a low-index Teflon interlayer with an EQE of 36%, which is 29% higher than an optimized planar OLED. By experimentally measuring the OLED air mode dispersion, we confirm the cavity emission of a corrugated OLED is enhanced by the low index layer.

Supercurrent Flow in Multiterminal Graphene Josephson Junctions.

We investigate the electronic properties of ballistic planar Josephson junctions with multiple superconducting terminals. Our devices consist of monolayer graphene encapsulated in boron nitride with molybdenum-rhenium contacts. Resistance measurements yield multiple resonant features, which are attributed to supercurrent flow among adjacent and nonadjacent Josephson junctions. In particular, we find that superconducting and dissipative currents coexist within the same region of graphene. We show that the presence of dissipative currents primarily results in electron heating and estimate the associated temperature rise. We find that the electrons in encapsulated graphene are efficiently cooled through the electron-phonon coupling.

Economic analysis and life cycle impact assessment of municipal solid waste (MSW) disposal: A case study of Mumbai, India.

Municipal solid waste (MSW) management is a major concern in Indian cities. This work rigorously assesses the relative costs and the environmental and health benefits of alternative MSW management methods. Management of MSW over the next 20 years for the city of Greater Mumbai was considered. A generic model was developed to determine the costs for (i) dumping on open ground, (ii) sanitary landfill without leachate treatment, (iii) landfilling with leachate treatment and (iv) regional composting and landfilling. LandGEM was used to quantify the gaseous emissions from landfill, while emissions from leachate and composting were taken from literature. The life cycle impact model of one tonne of MSW was developed using OpenLCA software and the International Reference Life Cycle Data System (ILCD) 2011 method was used for impact assessment. The cost of disposal of one tonne of waste was found to be INR344 (US$5.17), INR741 (US$11.13) and INR1367 (US$20.53), respectively, for the first three scenarios. As compared to open dumping, landfill gas flaring reduced the global warming potential by 32% and leachate treatment reduced freshwater ecotoxicity and total human toxicity marginally, by 20% and 60%, respectively. Composting-landfilling was the most preferred option, with a cost of INR531 tonne-1 (US$7.97), leading to a reduction in global warming potential by 79% and a slight decrease in freshwater ecotoxicity by 64%. Further, emissions due to accidental fires were also quantified. The study provides valuable insights for the selection of MSW management options for large metropolitan cities in developing countries.

Effective Remediation of Groundwater Fluoride with Inexpensively Processed Indian Bauxite.

India represents one-third of the world's fluorosis burden and is the fifth global producer of bauxite ore, which has previously been identified as a potential resource for remediating fluoride-contaminated groundwater in impoverished communities. Here, we use thermal activation and/or groundwater acidification to enhance fluoride adsorption by Indian bauxite obtained from Visakhapatnam, an area proximate to endemic fluorosis regions. We compare combinatorial water treatment and bauxite-processing scenarios through batch adsorption experiments, material characterization, and detailed cost analyses. Heating Indian bauxite above 300 °C increases available surface area by > 15× (to ∼170 m2/g) through gibbsite dehydroxylation and reduces the bauxite dose for remediating 10 ppm F- to 1.5 ppm F- by ∼93% (to 21 g/L). Additionally, lowering groundwater pH to 6.0 with HCl or CO2 further reduces the average required bauxite doses by 43-73% for ores heated at 300 °C (∼12 g/L) and 100 °C (∼77 g/L). Product water in most examined treatment scenarios complies with EPA standards for drinking water (e.g., As, Cd, Pb, etc.) but potential leaching of Al, Mn, and Cr is of concern in some scenarios. Among the defluoridation options explored here, bauxite heated at 300 °C in acidified groundwater has the lowest direct costs ($6.86 per person per year) and material-intensity.

Microwave-Assisted, Asymmetric Synthesis of 3-Amino-2,3-Dihydrobenzofuran Flavonoid Derivatives from Chalcones.

A route to access 3-amino-2,3-dihydrobenzofurans that utilizes microwave-assisted organic synthesis to rapidly generate analogues has been developed. The route begins with an acid-catalyzed, microwave-assisted aldol condensation to generate chalcone intermediates, followed by a Corey-Bakshi-Shibata reduction and subsequent Sharpless asymmetric epoxidation to access stereoisomeric epoxyalcohols. The final step is a one-pot, microwave-assisted, regioselective, acid-catalyzed epoxide opening with various amines followed by an intramolecular nucleophilic aromatic substitution reaction to generate the 3-amino-2,3-dihydrobenzofurans. This route provides ready access to stereochemically and structurally diverse analogues of these flavonoid scaffolds. Additionally, a pilot library was synthesized, and the biological activity diversity of the chalcones and dihydrobenzofurans was explored in human carcinoma cell lines.

Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell-Derived Exosomes From Pediatric Patients.

RATIONALE: Studies have demonstrated that exosomes can repair cardiac tissue post-myocardial infarction and recapitulate the benefits of cellular therapy. OBJECTIVE: We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia-reperfusion injury. METHODS AND RESULTS: Human CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions. Exosomes were isolated from the culture-conditioned media and delivered to athymic rats after ischemia-reperfusion injury. Echocardiography at day 3 post-myocardial infarction suggested statistically improved function in neonatal hypoxic and neonatal normoxic groups compared with saline-treated controls. At 28 days post-myocardial infarction, exosomes derived from neonatal normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly improved cardiac function compared with those from saline-treated controls. Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups compared with controls. Finally, using sequencing data, a computational model was generated to link microRNA levels to specific outcomes. CONCLUSIONS: CPC exosomes derived from neonates improved cardiac function independent of culture oxygen levels, whereas CPC exosomes from older children were not reparative unless subjected to hypoxic conditions. Cardiac functional improvements were associated with increased angiogenesis, reduced fibrosis, and improved hypertrophy, resulting in improved cardiac function; however, mechanisms for normoxic neonatal CPC exosomes improved function independent of those mechanisms. This is the first study of its kind demonstrating that donor age and oxygen content in the microenvironment significantly alter the efficacy of human CPC-derived exosomes.