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Obesity is a metabolic disease and causes significant changes in host and gut microbial metabolite levels. However, little research has been done on the relationship between host and gut microbial metabolites. Thus, this study investigated the connection of the chemicals, based on the different effects of two Inonotus obliquus extracts on high-fat-diet-induced mice and their mechanisms. In this study, C57BL6/J mice fed with a high-fat diet were given I. obliquus ethanol extract (IOE) and polysaccharide (IOP). 1H NMR-based metabolomics, 16S rRNA sequencing, and real-time reverse transcription polymerase chain reaction (RT-PCR) were used to detect metabolites, cecal microbes, and expressions of genes in liver. IOE and IOP effectively improved the obesity of mice, including the adjustment of body weight gain, energy intake, energy efficiency, liver glucose metabolism and triglyceride metabolism, tricarboxylic acid (TCA) cycle, and degradation of three major nutrients (carbohydrate, lipid, and protein). IOE significantly increased cecal propionate based on Bacteroides and Akkermansia, thereby inhibiting energy intake and fat accumulation in mice. IOP remarkably improved the level of cecal butyrate by Lactobacillus and the Bacteroidales S24-7 group, resulting in increased energy consumption, and fat degradation by regulating the TCA cycle of the host. Two extracts containing different bioactive substances of I. obliquus improved obesity in mice through different effects on production of cecal microbial metabolites. Moreover, cecal butyrate (not propionate) was connected with chemicals of mice, including four metabolites of the TCA cycle and other metabolism-related chemicals.

The performance of photovoltaic devices based on blends of conjugated polymers with nonfullerene acceptors depends on the phase behavior and microstructure of the binary, which in turn depends on the chemical structures of the molecular components and the blend composition. We investigate the correlation between the molecular structure, composition, phase behavior, and device performance of a model system consisting of semicrystalline poly-3-hexylthiophene (P3HT) as the donor polymer and three nonfullerene acceptors, two of which (O-IDTBR/EH-IDTBR) have a planar core with different side chains and one (O-IDFBR) of which has a twisted core. We combine differential scanning calorimetry with optical measurements including UV–Vis spectroscopy, photoluminescence, spectroscopic ellipsometry, and Raman spectroscopy and photovoltaic device performance measurements, all at varying blend composition. For P3HT:IDTBR blends, the crystallinity of polymer and acceptor is preserved over a wide composition range and the blend displays a eutectic phase behavior, with the optimum solar cell composition lying close to the eutectic composition. For P3HT:IDFBR blends, increasing acceptor content disrupts the polymer crystallinity, and the optimum device composition appears to be limited by polymer connectivity rather than being linked to the eutectic composition. The optical probes allow us to probe both the crystalline and amorphous phases, clearly revealing the compositions at which component mixing disrupts crystallinity., E.R. is grateful to the Fonds de Recherche du Quebec-Nature et technologies (FRQNT) for a postdoctoral fellowship and acknowledges the financial support from the European Cooperation in Science and Technology. J.N. acknowledges the financial support from the Engineering and Physical Science Research Council (grants nos. EP/P005543/1, EP/ R023581/1, and EP/P032591/1) and from the European Research Council for funding (grant agreement no. 742708). J.N. and E.R. thank the Helmholtz Foundation for a Helmholtz International Fellow Award. A.A.Y.G. thanks the EPSRC for a postdoctoral fellowship award (grant no. EP/P00928X/1). The authors at ICMAB would like to acknowledge the financial support from the Spanish Ministry of Economy, Industry and Competitiveness through the “Severo Ocho” Program for Centers of Excellence in R&D (SEV-2015-0496) and project reference PGC2018-095411-B-I00 as well as the European Research Council (ERC) under grant agreement no. 648901. I.M. acknowledges funding from KAUST, as well as EPSRC Project EP/G037515/1, EP/M005143/1, ECFP7 Project SC2 (610115), and EP/N509486/1 for the financial support.

Diabetes is affecting the life of millions of people. A large proportion of diabetic patients suffer from severe complications such as neuropathic pain, and current treatments for these complications have deleterious side effects. Thus, alternate therapeutic strategies are needed. Recently, the elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) was shown to reduce diabetic neuropathic pain in rodents. In this report, we describe a series of newly synthesized sEH inhibitors with at least 5-fold higher potency and doubled residence time inside both the human and rodent sEH enzyme than previously reported inhibitors. These inhibitors also have better physical properties and optimized pharmacokinetic profiles. The optimized inhibitor selected from this new series displayed improved efficacy of almost 10-fold in relieving pain perception in diabetic neuropathic rats as compared to the approved drug, gabapentin, and previously published sEH inhibitors. Therefore, these new sEH inhibitors could be an attractive alternative to treat diabetic neuropathy in humans.