Hypoglycemic, hypolipidemic and antioxidant effects of iridoid glycosides extracted from: Corni fructus: Possible involvement of the PI3K-Akt/PKB signaling pathway

Iridoid glycosides (CIG) are the major component of Corni fructus. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected. The results showed that CIG significantly improved oral glucose tolerance in diabetic mice. Biochemical indices also revealed that CIG had a positive effect on lipid metabolism and oxidative stress. In addition, CIG can significantly enhance the expression level of the PI3K-Akt/PKB pathway related proteins in skeletal muscle, which is the key pathway of insulin metabolism. These findings show that CIG can improve the hyperglycemia and hyperlipidemia of HFD-STZ-induced diabetic mice through the PI3K-Akt/PKB signaling pathway, and CIG might be a potential medicine or functional food for type 2 diabetes mellitus remedies. © 2018 The Royal Society of Chemistry

Energy transfer in multi-collision environments; an experimental test of theory: LiH (10;2) in H2(0;0)

We report separate experimental and theoretical studies that follow the equilibration of highly excited LiH (v=10;J=2) in H2 at 680K. Experiments that follow the time evolution of state-tostate population transfer in multi-collision conditions were carried out by Shen and co-workers at Xinjiang University and East China Institute of Science and Technology with µs resolution. At the same time, theoretical computations on the relaxation of this gas mixture were undertaken by McCaffery and co-workers at Sussex University. Rapid, near-resonant, vibration-vibration energy exchange is a marked feature of the initial relaxation process. However, at later stages of ensemble evolution, slower vibration-rotation transfer processes form the dominant relaxation mechanism. The physics of the decay process are complex and, as demonstrated experimentally here, a single exponential expression is unlikely to capture the form of this decay with any accuracy. When these separate studies were complete, the evolution of modal temperatures from the Sussex calculations were compared with experimental measurements of these same quantities from Shanghai and Urumqui. The two sets of data were found to be identical to within experimental and computational error. This constitutes an important experimental validation of the theoretical/computational model developed by the Sussex group and a significant experimental advance by the group of Shen et.al

Assessing Knowledge Editing in Language Models via Relation Perspective

Knowledge Editing (KE) for modifying factual knowledge in Large Language Models (LLMs) has been receiving increasing attention. However, existing knowledge editing methods are entity-centric, and it is unclear whether this approach is suitable for a relation-centric perspective. To address this gap, this paper constructs a new benchmark named RaKE, which focuses on Relation based Knowledge Editing. In this paper, we establish a suite of innovative metrics for evaluation and conduct comprehensive experiments involving various knowledge editing baselines. We notice that existing knowledge editing methods exhibit the potential difficulty in their ability to edit relations. Therefore, we further explore the role of relations in factual triplets within the transformer. Our research results confirm that knowledge related to relations is not only stored in the FFN network but also in the attention layers. This provides experimental support for future relation-based knowledge editing methods.Comment: Work in progres

Tumor-directed gene therapy in mice using a composite nonviral gene delivery system consisting of the piggyBac transposon and polyethylenimine

<p>Abstract</p> <p>Background</p> <p>Compared with viral vectors, nonviral vectors are less immunogenic, more stable, safer and easier to replication for application in cancer gene therapy. However, nonviral gene delivery system has not been extensively used because of the low transfection efficiency and the short transgene expression, especially <it>in vivo</it>. It is desirable to develop a nonviral gene delivery system that can support stable genomic integration and persistent gene expression <it>in vivo</it>. Here, we used a composite nonviral gene delivery system consisting of the <it>piggyBac </it>(PB) transposon and polyethylenimine (PEI) for long-term transgene expression in mouse ovarian tumors.</p> <p>Methods</p> <p>A recombinant plasmid PB [Act-RFP, HSV-tk] encoding both the herpes simplex thymidine kinase (HSV-tk) and the monomeric red fluorescent protein (mRFP1) under PB transposon elements was constructed. This plasmid and the PBase plasmid were injected into ovarian cancer tumor xenografts in mice by <it>in vivo </it>PEI system. The antitumor effects of HSV-tk/ganciclovir (GCV) system were observed after intraperitoneal injection of GCV. Histological analysis and TUNEL assay were performed on the cryostat sections of the tumor tissue.</p> <p>Results</p> <p>Plasmid construction was confirmed by PCR analysis combined with restrictive enzyme digestion. mRFP1 expression could be visualized three weeks after the last transfection of pPB/TK under fluorescence microscopy. After GCV admission, the tumor volume of PB/TK group was significantly reduced and the tumor inhibitory rate was 81.96% contrasted against the 43.07% in the TK group. Histological analysis showed that there were extensive necrosis and lymphocytes infiltration in the tumor tissue of the PB/TK group but limited in the tissue of control group. TUNEL assays suggested that the transfected cells were undergoing apoptosis after GCV admission <it>in vivo</it>.</p> <p>Conclusion</p> <p>Our results show that the nonviral gene delivery system coupling PB transposon with PEI can be used as an efficient tool for gene therapy in ovarian cancer.</p