Hepatic transcriptome discloses the potential targets of Xuefu Zhuyu Decoction ameliorating non-alcoholic fatty liver disease induced by high-fat diet.

Background and Aim: Xuefu Zhuyu decoction (XZD), a traditional Chinese medicinal formula, was firstly recorded in the Qing dynasty of ancient China and previously demonstrated to ameliorate hepatic steatosis. In the present study, the effects of XZD on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) were evaluated in mice and the hepatic transcriptome was detected to disclose the potential mechanisms of XZD. Experimental procedure: The effects of XZD (low- and high-dosage) on NAFLD induced by HFD for 16 weeks were evaluated. Obeticholic acid was used as control drug. Body weight, food intake and index of homeostatic model assessment for insulin resistance (HOMA-IR) were analyzed. Hepatic histology were observed in haematoxylin and eosin stained sections and quantified with NAFLD activity score (NAS). Lipid in hepatocytes was visualized by Oil red staining. Alanine aminotransferase (ALT) and hepatic triglyceride (TG) was measured. The hepatic transcriptom was detected with RNA-sequencing and validated with real-time polymerase chain reaction, western-blotting and hepatic quantitative metabolomics. Results: XZD ameliorated hepatic histology of NAFLD mice, accompanied with decreasing fasting insulin, HOMA-IR, NAS, ALT and hepatic TG. The hepatic transcriptom of NAFLD was significantly reversed by XZD treatment, especially the genes enriched in the pathways of arachidonic acid metabolism, fatty acid degradation, cytokine-cytokine receptor interaction and extracellular matrix (ECM) -receptor interaction. The hepatic quantitative metabolomics analysis confirmed fatty acid degradation as the key targeting pathway of XZD. Conclusions: XZD ameliorated NAFLD induced by HFD, which probably correlated closely to the pathways of fatty acid degradation.

HLCT-Type Acceptor Molecule-Based Exciplex System for Highly Efficient Solution-Processable OLEDs with Suppressed Efficiency Roll-Offs.

Exciplex systems are promising candidates for thermally activated delayed fluorescence (TADF) molecules because of the small energy difference between the lowest singlet and triplet excited states (ΔEST). However, realizing high-efficiency and low-external-quantum-efficiency (EQE) roll-off in solution-processed organic light-emitting diodes (OLEDs) using an exciplex system remains a formidable challenge. In this study, two (HLCT)-type isomers with a spiro skeleton, 2-tBuspoCz-TRZ and 10-tBuspoCz-TRZ, are designed and synthesized as acceptors of exciplexes, where tert-butylspirofluorene indole is regarded as a donor and the triazine unit as an acceptor. Green exciplex emissions are observed for the 2-tBuspoCz-TRZ:TAPC and 10-tBuspoCz-TRZ:TAPC exciplexes, indicating distinct TADF characteristics with a very small ΔEST of 35 ± 5 meV. By using the TADF exciplex system based on the HLCT acceptor as an emitter, solution-processable OLEDs achieve a maximum external quantum efficiency (EQEmax) of 20.8%. Furthermore, a high EQEmax > 25% with a very low-efficiency roll-off (≈3.5% at 1000 cd m-2) is obtained for solution-processable phosphorescent devices using HLCT-based exciplexes as the host matrix of phosphors. This study paves the way for a novel strategy for designing acceptor exciplex molecules for effective TADF molecules and host matrices in solution-processable OLEDs.

Hybridized local and charge transfer dendrimers with near-unity exciton utilization for enabling high-efficiency solution-processed hyperfluorescent OLEDs.

Achieving both high emission efficiency and exciton utilization efficiency (ηS) in hot exciton materials is still a formidable task. Herein, a proof-of-concept design for improving ηS in hot exciton materials is proposed via elaborate regulation of singlet-triplet energy difference, leading to an additional thermally activated delayed fluorescence (TADF) process. Two novel dendrimers, named D-TTT-H and D-TTT-tBu, were prepared and characterized, in which diphenylamine derivatives were used as a donor moiety and tri(triazolo)triazine (TTT) as an acceptor fragment. Compounds D-TTT-H and D-TTT-tBu showed an intense green color with an emission efficiency of approximately 80% in solution. Impressively, both dendrimers simultaneously exhibited a hot exciton process and TADF characteristic in the solid state, as was demonstrated via theoretical calculation, transient photoluminescence, magneto-electroluminescence and transient electroluminescence measurements, thus achieving almost unity ηS. A solution processable organic light-emitting diode (OLED) employing the dendrimer as a dopant represents the best performance with the highest luminance of 15090 cd m-2 and a maximum external quantum efficiency (EQEmax) of 11.96%. Moreover, using D-TTT-H as a sensitizer, an EQEmax of 30.88%, 24.08% and 14.33% were achieved for green, orange and red solution-processed OLEDs, respectively. This research paves a new avenue to construct a fluorescent molecule with high ηS for efficient and stable OLEDs.

Inhibition on XBP1s-driven lipogenesis by Qushi Huayu Decoction contributes to amelioration of hepatic steatosis induced by fructose.

ETHNOPHARMACOLOGICAL RELEVANCE: Qushi Huayu Decoction (QHD) is a traditional Chinese medicine formula consisting of five herbs, which has been used for non-alcoholic fatty liver disease (NAFLD) treatment in clinic for decades in China and validated in several NAFLD animal models. The hepatic de novo lipogenesis (DNL) is enhanced greatly to contribute to steatosis in NAFLD. The spliced form of X-box binding protein 1 (XBP1s) initiates DNL independently of sterol regulatory element-binding protein (SREBP) and carbohydrate-responsive element-binding protein (ChREBP). AIM OF THE STUDY: To disclose the mechanism of inhibition on hepatic DNL by QHD and the responsible compounds. METHODS: The effects of QHD on hepatic DNL were evaluated in mice induced by high-fructose diet (HFru). The effects of the serum-absorbed compounds of QHD on XBP1s were evaluated in HepG2 cells induced by tunicamycin. Hepatic histology, triglyceride (TG) and nonesterified fatty acids were observed. Hepatic apolipoprotein B100 and very low-density lipoprotein were measured to reflect lipid out-transport. The mRNA expression of XBP1s and its target genes were detected by real-time polymerase chain reaction. The protein expression of TG synthetases and DNL enzymes, and inositol requirement enzyme 1 alpha (IRE1α), phosphorylated IRE1α and XBP1s were detected in liver tissue and HepG2 cells by western-blot. The binding activity of SREBP1, protein expression of ChREBP and XBP1s were detected in the nuclear extracts of liver tissue. RESULTS: Dynamical observing suggested feeding with HFru for 2 weeks was sufficient to induce hepatic lipogenesis and XBP1s. QHD ameliorated liver steatosis without enhancing out-transport of lipids, accompanied with more inhibitory effects on DNL enzymes than TG synthetases. QHD inhibits the nuclear XBP1s without affecting ChREBP and SREBP1. In QHD, chlorogenic acid, geniposide and polydatin inhibit lipogenesis initiated by XPB1s. CONCLUSION: QHD probably decreases hepatic DNL by inhibiting XBP1s independent of SREBP1 and ChREBP. Chlorogenic acid, geniposide and polydatin are the potential responsible compounds.