Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

Superoxide dismutase reduces injury in many disease processes, implicating superoxide anion radical (02 ) as a toxic species in vivo. A critical target of superoxide may be nitric oxide (NO-) produced by endothelium, macrophages, neutrophils, and brain synaptosomes. Superoxide and NO-are known to rapidly react to form the stable peroxynitrite anion (ONOO-). We have shown that peroxynitrite has a pKa of 7.49 ± 0.06 at 3TC and rapidly decomposes once protonated with a half-life of 1.9 sec at pH 7.4. Peroxynitrite decomposition generates a strong oxidant with reactivity similar to hydroxyl radical, as assessed by the oxidation of deoxyribose or dimethyl sulfoxide. Product yields indicative of hydroxyl radical were 5.1 ± 0.1% and 24.3 + 1.0%, respectively, of added peroxynitrite. Product formation was not affected by the metal chelator diethyltriaminepentaacetic acid, suggesting that iron was not required to catalyze oxidation. In contrast, desferrioxamine was a potent, competitive inhibitor of peroxynitriteinitiated oxidation because of a direct reaction between desferrioxamine and peroxynitrite rather than by iron chelation. We propose that superoxide dismutase may protect vascular tissue stimulated to produce superoxide and NON under pathological conditions by preventing the formation of peroxynitrite.Vascular injury secondary to ischemia/reperfusion, inflammation, xenobiotic metabolism, hyperoxic exposure, and other diseases results in loss of endothelial barrier function, adhesion of platelets, and abnormal vasoregulation. The ability of superoxide dismutase (SOD) to often reduce endothelial injury indirectly implicates the participation of superoxide anion radical (Oj-) with many pathological processes (1). While O-' can be directly toxic (2), it has a limited reactivity with most biological molecules, raising questions about its toxicity per se (3). To account for the apparent toxicity of O-j in vivo, the secondary production of the far-more-reactive hydroxyl radical (HO-) is frequently proposed to occur by the iron-catalyzed Haber Recently, endothelium, macrophages, and brain synaptosome preparations have been shown to produce NOR by oxidizing arginine by a calcium-activated NADPH-dependent enzyme (6-9). NOR appears to be a major form of the endothelium-derived relaxing factor (EDRF) (10). Vasodilatory agents such as acetylcholine, ATP, and bradykinin initiate a receptor-mediated influx of Ca2 , triggering the production and extracellular release of NO-, which then activates soluble heme-containing guanylate cyclases to produce cGMP in vascular smooth muscle and platelets. Increased cGMP promotes relaxation in vascular smooth muscle and inhibits platelet aggregation as well as adhesion of platelets to endothelium (11). Macrophages produce NOR as part of their cytotoxic armamentarium (6).The half-life of EDRF and NON ranges from 4 to 50 sec (12), which is approximately doubled by SOD (13,14). NOR does not bind directly to the copper of SOD (15), suggesting that stabilization involves the scavenging of...

psychological protection of the mental health of medical workers has been initiated in China. The experiences from this public health emergency should inform the efficiency and quality of future crisis intervention of the Chinese Government and authorities around the world.

Because of the remarkably high theoretical energy output, metal-air batteries represent one class of promising power sources for applications in next-generation electronics, electrified transportation and energy storage of smart grids. The most prominent feature of a metal-air battery is the combination of a metal anode with high energy density and an air electrode with open structure to draw cathode active materials (i.e., oxygen) from air. In this critical review, we present the fundamentals and recent advances related to the fields of metal-air batteries, with a focus on the electrochemistry and materials chemistry of air electrodes. The battery electrochemistry and catalytic mechanism of oxygen reduction reactions are discussed on the basis of aqueous and organic electrolytes. Four groups of extensively studied catalysts for the cathode oxygen reduction/evolution are selectively surveyed from materials chemistry to electrode properties and battery application: Pt and Pt-based alloys (e.g., PtAu nanoparticles), carbonaceous materials (e.g., graphene nanosheets), transition-metal oxides (e.g., Mn-based spinels and perovskites), and inorganic-organic composites (e.g., metal macrocycle derivatives). The design and optimization of air-electrode structure are also outlined. Furthermore, remarks on the challenges and perspectives of research directions are proposed for further development of metal-air batteries (219 references).