Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type- and Sex-specific Effects during Development in Mice.

BACKGROUND: Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell type-specific information after sevoflurane exposure limits the mechanistic understanding of these effects. In this study, the authors tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type-specific effects in mice of both sexes. METHODS: Neonatal mice were exposed to 3% sevoflurane for 2 h at postnatal days 6, 8, and 10 and analyzed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. The Morris Water Maze test was performed to test neurocognitive function. RESULTS: The authors found sex-specific distribution of hippocampal cell types in control mice alongside cell type- and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice after sevoflurane exposure regarding the proportions of cornu ammonis 1 neurons (control vs. sevoflurane, males: 79.9% vs. 32.3%; females: 27.3% vs. 24.3%), dentate gyrus (males: 4.2% vs. 23.4%; females: 36.2% vs. 35.8%), and oligodendrocytes (males: 0.6% vs. 6.9%; females: 5.9% vs. 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand-receptor pairs in the cornu ammonis 1, cornu ammonis 3, and dente gyrus trisynaptic circuit (control vs. sevoflurane, cornu ammonis 1-cornu ammonis 3: 18 vs. 42 in males and 15 vs. 21 in females; cornu ammonis 1-dentate gyrus: 21 vs. 35 in males and 12 vs. 20 in females; cornu ammonis 3-dentate gyrus: 25 vs. 45 in males and 17 vs. 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased cornu ammonis 1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes. CONCLUSIONS: This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and nonneuronal cell type- and sex-specific effects of sevoflurane during development.

Novel cathode interlayers based on neutral alcohol-soluble small molecules with a triphenylamine core featuring polar phosphonate side chains for high-performance polymer light-emitting and photovoltaic devices.

A new family of neutral alcohol-soluble small molecular materials comprised of electron-rich triphenylamine (TPA) and fluorene featuring phosphonate side chains (FEP) is reported, namely 3TPA-FEP, 2TPA-2FEP and TPA-3FEP, which have different TPA and FEP contents. Due to their good solubility in polar solvents like alcohol, multilayer devices can be fabricated by a wet process from orthogonal solvents. Polymer light-emitting devices with these materials as a cathode interlayer and Al as the cathode show greatly enhanced efficiencies in contrast to control devices without such a cathode interlayer, and their efficiencies are comparable with or even higher than devices with the low work-function metal Ba/Al as the cathode. In addition, high-performance polymer solar cells based on the poly[N-9''-hepta-decanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT):[6,6]-phenyl C71 -butyric acid methyl ester (PC71 BM) system are also achieved with power conversion efficiencies of 7.21%, 6.90% and 6.89%, by utilizing 3TPA-FEP, 2TPA-2FEP and TPA-3FEP as the cathode interlayer, respectively. These efficiencies are also much higher than those for control devices without the cathode interlayer. Although TPA is well-known as a hole-transport unit, the current findings indicate that alcohol-soluble TPA-based small molecules are also a promising cathode interlayer for both electron injection and extraction.