No abstract

Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) has reached epidemic proportions with no pharmacological therapy approved. Lower circulating glycine is consistently reported in patients with NAFLD, but the causes for reduced glycine, its role as a causative factor, and its therapeutic potential remain unclear. We performed transcriptomics in livers from humans and mice with NAFLD and found suppression of glycine biosynthetic genes, primarily alanine-glyoxylate aminotransferase 1 (AGXT1). Genetic (Agxt1−/− mice) and dietary approaches to limit glycine availability resulted in exacerbated diet-induced hyperlipidemia and steatohepatitis, with suppressed mitochondrial/peroxisomal fatty acid β-oxidation (FAO) and enhanced inflammation as the underlying pathways. We explored glycine-based compounds with dual lipid/glucose-lowering properties as potential therapies for NAFLD and identified a tripeptide (Gly-Gly-L-Leu, DT-109) that improved body composition and lowered circulating glucose, lipids, transaminases, proinflammatory cytokines, and steatohepatitis in mice with established NASH induced by a high-fat, cholesterol, and fructose diet. We applied metagenomics, transcriptomics, and metabolomics to explore the underlying mechanisms. The bacterial genus Clostridium sensu stricto was markedly increased in mice with NASH and decreased after DT-109 treatment. DT-109 induced hepatic FAO pathways, lowered lipotoxicity, and stimulated de novo glutathione synthesis. In turn, inflammatory infiltration and hepatic fibrosis were attenuated via suppression of NF-κB target genes and TGFβ/SMAD signaling. Unlike its effects on the gut microbiome, DT-109 stimulated FAO and glutathione synthesis independent of NASH. In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation.

No abstract

Interface engineering is imperative to boost the extraction capability in perovskite solar cells (PSCs). We propose a promising approach to enhance the electron mobility and charge transfer ability of tin oxide (SnO2) electron transport layer (ETL) by introducing a two-dimensional carbide (MXene) with strong interface interaction. The MXene-modified SnO2 ETL also offers a preferable growth platform for perovskite films with reduced trap density. Through a spatially resolved imaging technique, profoundly reduced non-radiative recombination and charge transport losses in PSCs based on MXene-modified SnO2 are also observed. As a result, the PSC achieves an enhanced efficiency of 20.65% with ultralow saturated current density and negligible hysteresis. We provide an in-depth mechanistic understanding of MXene interface engineering, offering an alternative approach to obtain efficient PSCs.

Osmanthus fragrans is an ornamental and economically important plant known for its magnificent aroma, and the most important aroma-active compounds in flowers are monoterpenes, mainly β-ocimene, linalool and linalool derivatives. To understand the molecular mechanism of monoterpene production, we analyzed the emission and accumulation patterns of these compounds and the transcript levels of the genes involved in their biosynthesis in two O. fragrans cultivars during flowering stages. The results showed that both emission and accumulation of monoterpenes varied with flower development and glycosylation had an important impact on floral linalool emission during this process. Gene expression demonstrated that the transcript levels of terpene synthase (TPS) genes probably played a key role in monoterpene production, compared to the genes in the MEP pathway. Phylogenetic analysis showed that OfTPS1 and OfTPS2 belonged to a TPS-g subfamily, and OfTPS3 and OfTPS4 clustered into a TPS-b subfamily. Their transient and stable expression in tobacco leaves suggested that OfTPS1 and OfTPS2 exclusively produced β-linalool, and trans-β-ocimene was the sole product from OfTPS3, while OfTPS4, a predictive sesquiterpene synthase, produced α-farnesene. These results indicate that OfTPS1, OfTPS2, and OfTPS3 could account for the major floral monoterpenes, linalool and trans-β-ocimene, produced in O. fragrans flowers.

10We construct a rock physics workflow to link elastic properties of shales to complex

Seismic anisotropy records past and present tectonic deformations and provides important constraints for understanding the structure and dynamics of the Earth's interior. In this work, we use tremendous amounts of high‐quality P wave arrival times from local and regional earthquakes to determine a high‐resolution tomographic model of 3‐D P wave azimuthal anisotropy down to 1,000‐km depth beneath East Asia. Our results show that trench‐parallel fast‐velocity directions (FVDs) are visible in the shallow portion of the subducting Pacific slab (<80 km), whereas the deeper portion of the Pacific slab mainly exhibits trench‐normal FVDs, except for the stagnant slab in the mantle transition zone (MTZ) where obvious NE‐SW FVDs are revealed. The FVDs in the subslab mantle change from a subduction‐parallel trend at depths of 80–400 km to a subduction‐normal trend in the MTZ. Large‐scale low‐velocity anomalies are revealed beneath the Philippine Sea plate where the FVD is NE‐SW. The FVDs along the Izu‐Bonin arc and in a slab gap exhibit a striking anticlockwise toroidal trend. All these features may reflect complex 3‐D flows in the mantle wedge due to tearing and dehydration processes of the subducting Pacific slab. The subducting Pacific slab is split at ~300‐km depth under the Bonin arc and then penetrates into the lower mantle, whereas under East Asia the Pacific slab becomes stagnant in the MTZ and reaches the North‐South Gravity Lineament in China. The intraplate volcanoes in East Asia are caused by hot and wet upwelling flows in the big mantle wedge above the stagnant Pacific slab.

To enhance the long stability of sulfur cathode for a high-energy lithium–sulfur cell, a thin wall hollow spherical structured polypyrrole (T-HSSP) composed of a mono layer of PPy nano-particles is employed as a host to encapsulate the sulfur component.