Cell-Based Metabolomics Approach for Anticipating and Investigating Cytotoxicity of Gold Nanorods

Despite the increasing application of gold nanoparticles, there has been little assessment of biological system toxicity to evaluate their potential impact on human health. In this study, the human hepatoma cell line (Hep G2) was used in a metabolomics approach to study the effects of shape, time, and dose of gold nanorods (GNRs). Using optimized parameters for chromatography and mass spectrometry, the metabolites detected by GC-MS were processed with MS DIAL and identified with Fiehnlib. Key metabolic pathways affected by GNRs were identified by endo-metabolic profiling of cells mixed with GNRs of varying shape while varying the dose and time of exposure. The shape of GNRs affected cytotoxicity, and short GNR (GNR-S) triggered disorder of cell metabolism. High concentrations of GNRs caused more significant toxicity. The cytotoxicity and bioTEM results illustrated that the mitochondria toxicity, as the main cytotoxicity of GNRs, caused declining cytoprotective ability. The mitochondrial dysfunction disrupted alanine, aspartate, glutamate, arginine, and proline metabolism, with amino acid synthesis generally downregulated. However, the efflux function of cells can exclude GNRs extracellularly within 24 h, resulting in reduced cell mitochondrial metabolic toxicity and allowing metabolic disorders to recover to normal function

Distributed Spectrum Sharing in Cognitive Radio Networks: A Pricing-Based Decomposition Approach

The limited radio spectrum has become a bottleneck for various wireless communications. To better utilize the scare radio spectrum, cognitive radios have recently attracted increasing attention, which makes spectrum sharing more viable. Sharing radio spectrum from primary users to secondary users is of great importance. A licensed primary user (PU) can lease its spectrum to secondary users (SUs) for wireless communications. This paper studies the problem of social welfare maximization of distributed spectrum sharing among a PU and SUs. We first formulate the problem of social welfare maximization which takes into account both the cost of the PU and the utility gained by each SU. The social welfare maximization is a convex optimization problem and thus can be solved by a centralized algorithm. However, the utility function of each SU may contain the private information. To avoid privacy leakage of SUs, we propose an iterative distributed algorithm based on a pricing-based decomposition framework. It is theoretically proved that our algorithm converges to the optimal solution. Simulation results are presented to show that our algorithm achieves the optimal social welfare and converges quickly in a practical setting

Cardioprotective Effect of Danshensu against Ischemic/Reperfusion Injury via c-Subunit of ATP Synthase Inhibition

Mitochondrial permeability transition pore (MPTP) opening is the main culprit of ischemic/reperfusion (IR) injury. It is reported that c-subunit of ATP synthase is the core component of MPTP. Danshensu (DSS), a monomer isolated from the traditional Chinese herb Danshen, has showed cardioprotective effect against IR injury through unknown mechanism. In this study, rat hearts were suspended in Langendorff instrument and perfused with Krebs-Henseleit (KH) buffer containing DSS for 60 minutes, followed by 30 minutes of global ischemia. Parameters including heart rate, left ventricular developed pressure, and the rate of left ventricle diastolic pressure change were recorded to assess their cardiac function. All these indexes were improved in DSS group. The rate of cardiomyocytes apoptosis and MPTP opening were both inhibited in DSS group. In addition, DSS administration leads to downregulation of c-subunit of ATP synthase in both mRNA and protein levels. Consistently, when c-subunit of ATP synthase was overexpressed in H9C2 cells through pcDNA3/5G1 plasmid transfection, MPTP opening was enhanced when the cardioprotective effect of DSS also tapers. In conclusion, DSS could alleviate cardiac IR injury via inhibiting c-subunit of ATP synthase expression

Recent Developments of High-Resolution Chemical Imaging Systems Based on Light-Addressable Potentiometric Sensors (LAPSs)

A light-addressable potentiometric sensor (LAPS) is a semiconductor electrochemical sensor based on the field-effect which detects the variation of the Nernst potential on the sensor surface, and the measurement area is defined by illumination. Thanks to its light-addressability feature, an LAPS-based chemical imaging sensor system can be developed, which can visualize the two-dimensional distribution of chemical species on the sensor surface. This sensor system has been used for the analysis of reactions and diffusions in various biochemical samples. In this review, the LAPS system set-up, including the sensor construction, sensing and substrate materials, modulated light and various measurement modes of the sensor systems are described. The recently developed technologies and the affecting factors, especially regarding the spatial resolution and temporal resolution are discussed and summarized, and the advantages and limitations of these technologies are illustrated. Finally, the further applications of LAPS-based chemical imaging sensors are discussed, where the combination with microfluidic devices is promising

Metabolic reprogramming of the glutathione biosynthesis modulates the resistance of Salmonella Derby to ceftriaxone

Summary: Salmonella, a foodborne pathogen, has become a major public health concern because of its widespread drug resistance, including resistance to multiple drugs such as third-generation cephalosporin, ceftriaxone (CRO). However, the metabolic profile changes and associated mechanisms engendered by cephalosporin-resistant mutations remain uncharted. In this study, we have employed the LC-MS/MS metabolomics platform to determine the metabolic profiles of 138 strains of Salmonella. Our results show that metabolic profiles correspond to specific serotypes, sources, processing stages, and antibiotic resistance patterns. Notably, we observed that Salmonella Derby (S. Derby) with drug resistance to CRO has a different metabolic status with changes in glutathione biosynthesis. Specifically, glutathione oxidized (GSSG) and citrulline abundances are greatly suppressed in CRO-resistant S. Derby. Furthermore, exogenous GSSG or citrulline, but not glutathione reduced (GSH), restored the susceptibility of multidrug-resistant S. Derby to CRO. This study establishes a strategy based on functional metabolomics to manage the survival of antibiotic-resistant bacteria