Thiazolidinediones Cause Cardiotoxicity via PPARγ- Independent Mechanism

Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are highly effective antidiabetic drugs that are widely used to treat type 2 diabetes mellitus (T2DM) due to their unique beneficial actions, such as a renoprotective effect, amelioration of glucose homeostasis, and blood pressure lowering, that other antidiabetic drugs do not have. Those beneficial actions, however, are shadowed by the increased risks of cardiovascular adverse events, including mitochondrial dysfunction, oxidative stress and myocardial energy deficiency, fluid retention, congestive heart failure, and myocardial infarction. Except PPARγ, TZDs also have affinity to numerous non-PPARγ targets in mitochondria, cytosol, and cytoplasm, including MitoNEET, mitochondrial pyruvate carrier, dehydrogenases involved in tricarboxylic acid cycle and electron transport, cytoplasmic ion channels, Na-K-pump, and other unknown enzymes. By binding to these targets, TZDs produce off-target effects and potentially increase cardiotoxicity. In this chapter, we review recent studies, both experimental and clinical, on the myocardial adverse effects associated with TZDs and their underlying mechanisms. We focus our review in large part on the relationship between these myocardial adverse effects and PPARγ

Splitting of surface defect partition functions and integrable systems

We study Bethe/gauge correspondence at the special locus of Coulomb moduli where the integrable system exhibits the splitting of degenerate levels. For this investigation, we consider the four-dimensional pure $\mathcal{N}=2$ supersymmetric $U(N)$ gauge theory, with a half-BPS surface defect constructed with the help of an orbifold or a degenerate gauge vertex. We show that the non-perturbative Dyson-Schwinger equations imply the Schr\"odinger-type and the Baxter-type differential equations satisfied by the respective surface defect partition functions. At the special locus of Coulomb moduli the surface defect partition function splits into parts. We recover the Bethe/gauge dictionary for each summand.Comment: 34 pages, 2 figures; v2. published versio

Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 ( S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study

Adsorption and determination of polycyclic aromatic hydrocarbons in water through the aggregation of graphene oxide

In this study, a simple method was developed for the aggregation of graphene oxide (GO) with the addition of NaCl to concentrate and separate polycyclic aromatic hydrocarbons (PAHs) from water samples, and this method was used as a environmentally friendly method for the determination of PAHs. We demonstrate the uniform dispersion of GO sheets in aqueous samples for the fast high-efficiency adsorption of PAHs. Aggregation occurred immediately upon elimination of electrostatic repulsion by adding NaCl to neutralize the excessive negative charges on the surfaces of the GO sheets. The aggregates of GO and PAHs were separated and treated with hexane to form a slurry. The slurry was filtered and subjected to gas chromatography–mass spectroscopy (GC-MS) analysis. Based on a 40-mL sample volume, limits of detection of 10–30 ng L-1 were obtained for 16 PAHs, with correlation coefficients (R2) exceeding 0.99. The method yielded good recovery, ranging from 80 to 111% and 80 to 107% for real spiked water samples at 100 and 500 ng L-1, respectively. Compared to traditional solid-phase extraction and liquid–liquid extraction methods, this method is free of organic reagents in the pretreatment procedure and uses only 1 mL hexane for sample introduction

Maternal Daidzein Supplementation during Lactation Promotes Growth Performance, Immunity, and Intestinal Health in Neonatal Rabbits

The main purpose of the present research was to evaluate the effect of varying levels of DA inclusion in maternal diet, in the form of powder, on the born-weaning growth performance (days 1–30) and intestinal health of neonatal rabbits. A total of 152 delivered maternal does (3.94 ± 0.05 kg) were allocated into four groups, with thirty-eight replicates of one doe each, and fed with a control diet (CON) supplemented with different levels of powdered DA (85 mg/kg (DA85), 170 mg/kg (DA170), and 340 mg/kg (DA340)) during lactation. The results show that dietary DA increased individual body weight at days 21 and 30 (p = 0.03 and p p p = 0.05) and glutathione peroxidase (GSH-Px) (p = 0.01) concentrations of maternal rabbits were increased in all maternal DA-supplemented groups and showed a linear and quadratic effect (p p p p p = 0.01) in neonatal rabbits were increased in all dietary DA groups, and both showed a linear and quadratic effect (p p = 0.03) and catalase (CAT) (p = 0.04) concentrations were affected by DA supplements, but linear and quadratic effects were only observed in the catalase (CAT) of neonatal rabbits (p p p = 0.01) and the ratio of villus height to crypt depth (p = 0.02 and p = 0.01) in neonatal rabbits were elevated in all DA-supplemented treatments, while a linear and quadratic effect was observed in jejunum, but a quadratic effect was observed in duodenum (p p p p = 0.04), zonula occludens-1 (ZO-1) (p p = 0.03), and solute carrier family 5 member 9 (SCL5A9) (p p p = 0.01, p = 0.04, and p p = 0.04, p = 0.04, and p = 0.03) epithelium were decreased in the DA170 and DA340 groups (p p < 0.05). In summary, as a functional additive, maternal DA supplementation with 170 and 340 mg/kg DA during lactation can promote the growth of neonatal rabbits, which is related to improved antioxidative capacity and immunity, as well as improved intestinal health in neonatal rabbits

Crystallization Behaviors of Anosovite and Silicate Crystals in High CaO and MgO Titanium Slag

Electric-furnace smelting has become the dominant process for the production of the titanium slag from ilmenite in China. The crystallization behaviors of anosovite and silicate crystals in the high CaO and MgO titanium slag were studied to insure smooth operation of the smelting process and the efficient separation of titanium slag and metallic iron. The crystallization behaviors were studied by a mathematical model established in this work. Results show that the crystallization order of anosovite and silicate crystals in high CaO and MgO titanium slag during cooling is: Al2TiO5 &gt; Ti3O5 &gt; MgTi2O5 &gt; MgSiO3 &gt; CaSiO3 &gt; FeTi2O5 &gt; Mn2SiO4 &gt; Fe2SiO4. Al2TiO5 and Ti3O5 have higher crystallization priority and should be responsible for the sharp increase in viscosity of titanium slag during cooling. The total crystallization rates of anosovite and silicate crystals are mainly controlled by Al2TiO5 and MgSiO3, respectively. The mass ratio of Ti2O3/&Sigma;TiO2 has a prominent influence on the total crystallization rate of anosovite crystals while the mass ratio of MgO/FeO has a slight influence on the total crystallization rate of anosovite crystals

ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data

Abstract Background Insecticide resistance is a substantial problem in controlling agricultural and medical pests. Detecting target site mutations is crucial to manage insecticide resistance. Though PCR-based methods have been widely used in this field, they are time-consuming and inefficient, and typically have a high false positive rate. Acetylcholinesterases (Ace) is the neural target of the widely used organophosphate (OP) and carbamate insecticides. However, there is not any software available to detect insecticide resistance associated mutations in RNA-Seq data at present. Results A computational pipeline ACE was developed to detect resistance mutations of ace in insect RNA-Seq data. Known ace resistance mutations were collected and used as a reference. We constructed a Web server for ACE, and the standalone software in both Linux and Windows versions is available for download. ACE was used to analyse 971 RNA-Seq data from 136 studies in 7 insect pests. The mutation frequency of each RNA-Seq dataset was calculated. The results indicated that the resistance frequency was 30%–44% in an eastern Ugandan Anopheles population, thus suggesting this resistance-conferring mutation has reached high frequency in these mosquitoes in Uganda. Analyses of RNA-Seq data from the diamondback moth Plutella xylostella indicated that the G227A mutation was positively related with resistance levels to organophosphate or carbamate insecticides. The wasp Nasonia vitripennis had a low frequency of resistant reads (<5%), but the agricultural pests Chilo suppressalis and Bemisia tabaci had a high resistance frequency. All ace reads in the 30 B. tabaci RNA-Seq data were resistant reads, suggesting that insecticide resistance has spread to very high frequency in B. tabaci. Conclusions To the best of our knowledge, the ACE pipeline is the first tool to detect resistance mutations from RNA-Seq data, and it facilitates the full utilization of large-scale genetic data obtained by using next-generation sequencing