Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis

cmFSM: a scalable CPU-MIC coordinated drug-finding tool by frequent subgraph mining

Abstract Background Frequent subgraphs mining is a significant problem in many practical domains. The solution of this kind of problem can particularly used in some large-scale drug molecular or biological libraries to help us find drugs or core biological structures rapidly and predict toxicity of some unknown compounds. The main challenge is its efficiency, as (i) it is computationally intensive to test for graph isomorphisms, and (ii) the graph collection to be mined and mining results can be very large. Existing solutions often require days to derive mining results from biological networks even with relative low support threshold. Also, the whole mining results always cannot be stored in single node memory. Results In this paper, we implement a parallel acceleration tool for classical frequent subgraph mining algorithm called cmFSM. The core idea is to employ parallel techniques to parallelize extension tasks, so as to reduce computation time. On the other hand, we employ multi-node strategy to solve the problem of memory constraints. The parallel optimization of cmFSM is carried out on three different levels, including the fine-grained OpenMP parallelization on single node, multi-node multi-process parallel acceleration and CPU-MIC collaborated parallel optimization. Conclusions Evaluation results show that cmFSM clearly outperforms the existing state-of-the-art miners even if we only hold a few parallel computing resources. It means that cmFSM provides a practical solution to frequent subgraph mining problem with huge number of mining results. Specifically, our solution is up to one order of magnitude faster than the best CPU-based approach on single node and presents a promising scalability of massive mining tasks in multi-node scenario. More source code are available at:Source Code: https://github.com/ysycloud/cmFSM

2,6-Dibenzhydryl-N-(2-Phenyliminoacenaphthylenylidene)-4-Chloro-Aniline Nickel Dihalides: Synthesis, Characterization and Ethylene Polymerization for Polyethylenes with High Molecular Weights

A series of 2,6-dibenzhydryl-N-(2-phenyliminoacenaphthylenylidene)-4- chloroanilines (L1-L5) and their nickel halide complexes LNiX (X = Br, C1-C5; X = Cl, C6-C10) were synthesized. All organic compounds were characterized by FT-IR and NMR spectroscopy and elemental analysis. The nickel complexes were characterized by FT-IR spectroscopy, elemental analysis and their structures were determined by single-crystal X-ray diffraction. Upon activation with MAO, all of these nickel complexes showed high activities (up to 10 7 g of PE (mol of Ni)-1 h-1) for ethylene polymerization. The resulting polyethylenes possess high molecular weights (Mw up to 106 g mol-1) and feature high degrees of branching. The MM-QEq method was employed to assess the ligands\u27 effects on catalytic activities. The results show that higher net charges on the nickel core correlate directly with higher measured activities

Cdyl2-60aa encoded by CircCDYL2 accelerates cardiomyocyte death by blocking APAF1 ubiquitination in rats

Abstract The loss of cardiomyocytes (CMs) after myocardial infarction (MI) is widely acknowledged to initiate the development of heart failure (HF). Herein, we found that circCDYL2 (583 nt) derived from chromodomain Y-like 2 (Cdyl2) is significantly upregulated in vitro (oxygen-glucose deprivation (OGD)-treated CMs) and in vivo (failing heart post-MI) and can be translated into a polypeptide termed Cdyl2-60aa (~7 kDa) in the presence of internal ribosomal entry sites (IRES). Downregulation of circCDYL2 significantly decreased the loss of OGD-treated CMs or the infarcted area of the heart post-MI. Additionally, elevated circCDYL2 significantly accelerated CM apoptosis via Cdyl2-60aa. We then discovered that Cdyl2-60aa could stabilize protein apoptotic protease activating factor-1 (APAF1) and promote CM apoptosis; heat shock protein 70 (HSP70) mediated APAF1 degradation in CMs by ubiquitinating APAF1, which Cdyl2-60aa could competitively block. In conclusion, our work substantiated the claim that circCDYL2 could promote CM apoptosis via Cdyl2-60aa, which enhanced APAF1 stability by blocking its ubiquitination by HSP70, suggesting that it is a therapeutic target for HF post-MI in rats

Methylene-bridged bimetallic α-diimino nickel(ii) complexes: Synthesis and high efficiency in ethylene polymerization

A series of 1,2-bis(arylimino)acenaphthylidenes (L1-L5) and their corresponding 4,4′-methylenebis(1-(2,6-diisopropylphenylimino)-2- (arylimino)acenaphthylene) derivatives (L6-L10) were synthesized and used to form mono-nuclear nickel bromides LnNiBr2 (n = 1-5, Ni1-Ni5) and bi-nuclear nickel halides LnNi2X4 (n = 6-10: X = Br, Ni2-1-Ni2-5; n = 4, X = Cl, Ni2-6). All the organic compounds were fully characterized by FT-IR spectra, NMR measurements and elemental analysis. The nickel complexes were characterized by FT-IR spectra and elemental analysis and the molecular structures of the representative complexes Ni1, Ni2-1 and Ni2-3 were confirmed by single-crystal X-ray diffraction. Upon activation with either Et2AlCl or MAO, all the nickel complex pre-catalysts exhibited high activity toward ethylene polymerization over the temperature range from ambient to 50 °C. In general, the bi-nuclear complexes showed a positive synergetic effect with higher activity than their mono nuclear analogs. The resultant polyethylene possessed higher molecular weight and a high degree of branching. © 2013 The Royal Society of Chemistry

An Improved Approach for Soil Moisture Estimation in Gully Fields of the Loess Plateau Using Sentinel-1A Radar Images

As an essential ecological parameter, soil moisture is important for understanding the water exchange between the land surface and the atmosphere, especially in the Loess Plateau (China). Although Synthetic Aperture Radar (SAR) images can be used for soil moisture retrieval, it is still a challenge to mitigate the impacts of complex terrain over hilly areas. Therefore, the objective of this paper is to propose an improved approach for soil moisture estimation in gully fields based on the joint use of the Advanced Integral Equation Model (AIEM) and the Incidence Angle Correction Model (IACM) from Sentinel-1A observations. AIEM is utilized to build a simulation database of microwave backscattering coefficients from various radar parameters and surface parameters, which is the data basis for the retrieval modeling. IACM is proposed to correct the deviation between the local incidence angle at the scatterer and the radar viewing angle. The study area is located in the Loess Plateau of China, where the main land cover is mostly bare land and the terrain is complex. The Sentinel-1A SAR data in C-band with dual polarization acquired on October 19th, 2017 was adopted to extract the VV&VH polarimetric backscattering coefficients. The in situ measurements of soil moisture were collected on the same day of the SAR acquisition, for evaluating the accuracy of the SAR-derived soil moisture. The results showed that, firstly, the estimated soil moisture with volumetric content between 0% and 20% was in the majority. Subsequently, both the RMSE of estimation values (0.963%) and the standard deviation of absolute errors (0.957%) demonstrated a good accuracy of the improved approach. Moreover, the evaluation of IACM confirmed that the improved approach coupling IACM and AIEM was more efficient than employing AIEM solely. In conclusion, the proposed approach has a strong ability to estimate the soil moisture in the gully fields of the Loess Plateau from Sentinel-1A data

Rim plate in the treatment of hyperextension tibial plateau fracture: surgical technique and a series of cases

Abstract Background The existence of a “bare area” at the anterior plateau has been observed in cases where anteromedial and/or anterolateral proximal tibial locking plates are used for fixation in the treatment of hyperextension tibial plateau fractures (HTPF). The objective of this study is to introduce the rim plate fixation technique and evaluate its clinical efficacy. Methods A retrospective analysis was conducted on HTPF patients who underwent treatment with a combination of rim plate and proximal tibial locking plate at our hospital between April 2015 and December 2019. All patients were followed up for a minimum of one year. Open reduction and internal fixation were performed using anteromedial/posteromedial and/or anterolateral approaches for all cases. The surgical strategies employed for rim plate fixation were introduced, and both radiographic and clinical outcomes were assessed. Results Thirteen patients were enrolled in the study, with an average follow-up time of 4.3 years. Satisfactory reduction was achieved and radiographically maintained in all cases. Additionally, all patients exhibited satisfactory clinical functions, as evidenced by a mean hospital for special surgery (HSS) knee score of 96.2 ± 2.0 (range: 90–98). Furthermore, no wound complications or implant breakage were observed in this series. Conclusion The combination of the rim plate and proximal tibial plate proved to be an effective fixation configuration, resulting in satisfactory clinical outcomes

2-(1-(Arylimino)ethyl)-8-arylimino-5,6,7-trihydroquinolylcobalt dichloride: Synthesis and polyethylene wax formation

A series of 2-(1-(arylimino)ethyl)-8-arylimino-5,6,7-trihydroquinolylcobalt dichloride (aryl = 2,6-R1-4-R2C6H2) pre-catalysts were synthesized and structurally characterized by FT-IR and elemental analyses. The molecular structures of Co1 (R1 = Me, R 2 = H), Co2 (R1 = Et, R2 = H) and Co5 (R 1 = Et, R2 = Me) were determined by single-crystal X-ray diffraction analysis, and confirmed Co1 as a distorted trigonal bipyramidal geometry at the metal, whilst in Co2 and Co5 the metal is square-pyramidal. Upon treatment with either MAO or MMAO, all cobalt pre-catalysts exhibited highest activities at 60 °C for ethylene polymerization. The resultant polyethylenes, under optimization reaction parameters, possessed low molecular weight (waxes) and narrow polydispersity. © 2012 Elsevier B.V

Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway

Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cytokines, which may contribute to drug resistance. In current study, we utilized in vitro K562 co-culture model with BM stroma to investigate IM resistance. As a result, co-culturing of K562 with BM stroma was sufficient to cause resistance to IM, which was accompanied with the activation of hedgehog (Hh) signaling pathway and upregulation of BCR-ABL as well as its downstream proteins like phosphorylated Akt, Bcl-xL and survivin, etc. On the other hand, oroxyloside A (OAG), a metabolite of oroxylin A from the root of Scutellaria baicalensis Georgi, which had low toxic effect on K562 cells, was able to sensitize K562 cells co-cultured with BM stroma to IM treatment in vitro and in vivo. We observed that OAG suppressed Hh pathway and subsequently nuclear translocation of GLI1, followed by downregulation of BCR-ABL and its downstream effectors, thus facilitating IM to induce apoptosis of K562 cells. Together, BM microenvironment rendered K562 cells drug resistance through activating Hh signaling, however, OAG could overcome IM resistance of CML cells through inhibiting Hh-BCR-ABL axis in vitro and in vivo