Serial Metabolome Changes in a Prospective Cohort of Subjects with Influenza Viral Infection and Comparison with Dengue Fever

Influenza virus infection (IVI) and dengue virus infection (DVI) are major public health threats. Between IVI and DVI, clinical symptoms can be overlapping yet infection-specific, but host metabolome changes are not well-described. Untargeted metabolomics and targeted oxylipinomic analyses were performed on sera serially collected at three phases of infection from a prospective cohort study of adult subjects with either H3N2 influenza infection or dengue fever. Untargeted metabolomics identified 26 differential metabolites, and major perturbed pathways included purine metabolism, fatty acid biosynthesis and β-oxidation, tryptophan metabolism, phospholipid catabolism, and steroid hormone pathway. Alterations in eight oxylipins were associated with the early symptomatic phase of H3N2 flu infection, were mostly arachidonic acid-derived, and were enriched in the lipoxygenase pathway. There was significant overlap in metabolome profiles in both infections. However, differences specific to IVI and DVI were observed. DVI specifically attenuated metabolites including serotonin, bile acids and biliverdin. Additionally, metabolome changes were more persistent in IVI in which metabolites such as hypoxanthine, inosine, and xanthine of the purine metabolism pathway remained significantly elevated at 21–27 days after fever onset. This study revealed the dynamic metabolome changes in IVI subjects and provided biochemical insights on host physiological similarities and differences between IVI and DVI

Stabilization of ssRNA on Graphene Oxide Surface: An Effective Way to Design Highly Robust RNA Probes

RNA probes constitute an important class of functional nucleic acids (FNAs). However, because of their notorious vulnerability to enzymatic degradation, extremely careful and special protocols must be followed when dealing with RNA probes. To fully use the large number of RNA FNAs available for bioanalysis and biomedicine, it is important to explore effective methods to protect RNA probes from enzymatic digestion. In this work, we systematically demonstrate that graphene oxide (GO) can effectively protect RNA probes from enzymatic digestion. Based on this finding, we propose an effective way to design robust RNA biosensors by simply mixing RNA probes with GO for analysis of nucleic acids, proteins, and small molecules. The entire assay is sensitive, selective, rapid, and more importantly, does not require any special protocols. The ability to protect ssRNA from enzymatic digestion by GO offers an exciting new way to stabilize ssRNA, which will not only provide new opportunities to utilize the large number of currently available, yet rarely explored, RNA FNAs for bioanalysis but also offer a new solution to protect important ssRNA molecules, such as microRNA and antisense ssRNA, for a great variety of biomedical applications

One-Step Synthesis of Fluorescent Boron Nitride Quantum Dots via a Hydrothermal Strategy Using Melamine as Nitrogen Source for the Detection of Ferric Ions

A facile and effective approach for the preparation of functionalized born nitride quantum dots (BNQDs) with blue fluorescence was explored by the hydrothermal treatment of the mixture of boric acid and melamine at 200 °C for 15 h. The as-prepared BNQDs were characterized by transmission electron microscopy (TEM), high-resolution TEM, atomic force microscopy, X-ray photoelectron spectroscopy, UV–vis spectroscopy, and fluorescence spectroscopy. The single layered BNQDs with the average size of 3 nm showed a blue light emission under the illumination of the UV light. The BNQDs could be easily dispersed in an aqueous medium and applied as fluorescent probes for selective detection of Fe³⁺ with remarkable selectivity and sensitivity (the lowest detection limit was 0.3 μM). The fluorescence fiber imaging demonstrated that the as-prepared quantum dots could be used as a valuable fluorchrome. Therefore, the BNQDs could be envisioned for potential applications in many fields such as biocompatible staining, fluorescent probes, and biological labeling

Biostable L‑DNAzyme for Sensing of Metal Ions in Biological Systems

DNAzymes, an important type of metal ion-dependent functional nucleic acid, are widely applied in bioanalysis and biomedicine. However, the use of DNAzymes in practical applications has been impeded by the intrinsic drawbacks of natural nucleic acids, such as interferences from nuclease digestion and protein binding, as well as undesired intermolecular interactions with other nucleic acids. On the basis of reciprocal chiral substrate specificity, the enantiomer of D-DNAzyme, L-DNAzyme, could initiate catalytic cleavage activity with the same achiral metal ion as a cofactor. Meanwhile, by using the advantage of nonbiological L-DNAzyme, which is not subject to the interferences of biological matrixes, as recognition units, a facile and stable L-DNAzyme sensor was proposed for sensing metal ions in complex biological samples and live cells

Using Molecular Level Modification To Tune the Conductivity of Graphene Papers

Graphene's excellent electrical conductivity benefits from its highly conjugated structure. Therefore, the manipulation of graphene's electronic and mechanical properties should be realized by controlled destruction of its in-sheet conjugation. Here, we report the manipulation of the conductivity of graphene papers, at the molecular level, via either covalent bonding or π–π stacking interactions using either monofunctional or bifunctional molecules. The graphene papers can be tailored with controllable conductivity from around 100 to below 0.001 S/cm. The controlled destruction of the in-sheet graphene conjugation system using monoaryl diazonium salts (MDS) resulted in a tunable decrease in the graphene paper conductivity. However, when the graphene was modified with bifunctional aryl diazonium salts (BDS), a more subtle decrease in conductivity of the graphene papers was observed. It is suggested that the modification of the graphene with the bifunctional BDS linker showed more subtle changes in conductivity because of the between-sheet electron communication, thus boosting the collective graphene paper conductivity. Consequently, a bipyrene terminal molecular wire (BPMW) was also synthesized and used to modify the graphene sheets via π–π stacking interactions. The BPMW afforded graphene papers with better electrical conductivity than those modified with either MDS or BDS molecules

Comparative Analysis of Four Oxidized Guanine Lesions from Reactions of DNA with Peroxynitrite, Singlet Oxygen, and γ‑Radiation

Oxidative damage to DNA has many origins, including irradiation, inflammation, and oxidative stress, but the chemistries are not the same. The most oxidizable base in DNA is 2-deoxyguanosine (dG), and the primary oxidation products are 8-oxodG and 2-amino-imidazolone. The latter rapidly converts to 2,2-diamino-oxazolone (Ox), and 8-oxodG is further oxidized to spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). In this study, we have examined the dose–response relationship for the formation of the above four products arising in calf thymus DNA exposed to gamma irradiation, photoactivated rose bengal, and two sources of peroxynitrite. In order to carry out these experiments, we developed a chromatographic system and synthesized isotopomeric internal standards to enable accurate and precise analysis based upon selected reaction monitoring mass spectrometry. 8-OxodG was the most abundant products in all cases, but its accumulation was highly dependent on the nature of the oxidizing agent and the subsequent conversion to Sp and Gh. Among the other oxidation products, Ox was the most abundant, and Sp was formed in significantly greater yield than Gh

Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection

<div><p>Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5–7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management.</p></div

Box plots of representative differentially expressed metabolites between dengue fever (DF) and dengue hemorrhagic fever (DHF) patients during critical phase.

<p><b>A.</b> Chenodeoxyglycocholic acid <b>B.</b> Glycocholic acid <b>C.</b> Glycoursodeoxycholic acid <b>D.</b> Uric acid <b>E.</b> Hypoxanthine <b>F.</b> Uridine <b>G.</b> 3-Hydroxyoctanoyl carnitine <b>H.</b> 2-Octenoylcarnitine <b>I.</b> L-phenylalanine. Horizontal lines represent median value. * <i>p</i><0.05, ** <i>p</i><0.01, *** <i>p</i><0.001, by Mann-Whitney test. The statistical comparison was with DF levels.</p

Pearson correlation analysis reveals correlation of bile acids with aspartate transaminase (AST) and alanine transaminase (ALT) levels in the critical phase of infection.

<p>Pearson correlation analysis reveals correlation of bile acids with aspartate transaminase (AST) and alanine transaminase (ALT) levels in the critical phase of infection.</p

Identified differentially expressed metabolites between DF and DHF patients in the recovery phase of dengue infection.

<p>Identified differentially expressed metabolites between DF and DHF patients in the recovery phase of dengue infection.</p