Elevated branched-chain amino acid promotes atherosclerosis progression by enhancing mitochondrial-to-nuclear H2O2-disulfide HMGB1 in macrophages.

As the essential amino acids, branched-chain amino acid (BCAA) from diets is indispensable for health. BCAA supplementation is often recommended for patients with consumptive diseases or healthy people who exercise regularly. Latest studies and ours reported that elevated BCAA level was positively correlated with metabolic syndrome, diabetes, thrombosis and heart failure. However, the adverse effect of BCAA in atherosclerosis (AS) and its underlying mechanism remain unknown. Here, we found elevated plasma BCAA level was an independent risk factor for CHD patients by a human cohort study. By employing the HCD-fed ApoE-/- mice of AS model, ingestion of BCAA significantly increased plaque volume, instability and inflammation in AS. Elevated BCAA due to high dietary BCAA intake or BCAA catabolic defects promoted AS progression. Furthermore, BCAA catabolic defects were found in the monocytes of patients with CHD and abdominal macrophages in AS mice. Improvement of BCAA catabolism in macrophages alleviated AS burden in mice. The protein screening assay revealed HMGB1 as a potential molecular target of BCAA in activating proinflammatory macrophages. Excessive BCAA induced the formation and secretion of disulfide HMGB1 as well as subsequent inflammatory cascade of macrophages in a mitochondrial-nuclear H2O2 dependent manner. Scavenging nuclear H2O2 by overexpression of nucleus-targeting catalase (nCAT) effectively inhibited BCAA-induced inflammation in macrophages. All of the results above illustrate that elevated BCAA promotes AS progression by inducing redox-regulated HMGB1 translocation and further proinflammatory macrophage activation. Our findings provide novel insights into the role of animo acids as the daily dietary nutrients in AS development, and also suggest that restricting excessive dietary BCAA consuming and promoting BCAA catabolism may serve as promising strategies to alleviate and prevent AS and its subsequent CHD.

Transition-metal-like bonding behaviors of a boron atom in a boron-cluster boronyl complex [(η7-B7)-B-BO].

Boron displays many unusual structural and bonding properties due to its electron deficiency. Here we show that a boron atom in a boron monoxide cluster (B9O-) exhibits transition-metal-like properties. Temperature-dependent photoelectron spectroscopy provided evidence of the existence of two isomers for B9O-: the main isomer has an adiabatic detachment energy (ADE) of 4.19 eV and a higher energy isomer with an ADE of 3.59 eV. The global minimum of B9O- is found surprisingly to be an umbrella-like structure (C 6v, 1A1) and its simulated spectrum agrees well with that of the main isomer observed. A low-lying isomer (C s, 1A') consisting of a BO unit bonded to a disk-like B8 cluster agrees well with the 3.59 eV ADE species. The unexpected umbrella-like global minimum of B9O- can be viewed as a central boron atom coordinated by a η7-B7 ligand on one side and a BO ligand on the other side, [(η7-B7)-B-BO]-. The central B atom is found to share its valence electrons with the B7 unit to fulfill double aromaticity, similar to that in half-sandwich [(η7-B7)-Zn-CO]- or [(η7-B7)-Fe(CO)3]- transition-metal complexes. The ability of boron to form a half-sandwich complex with an aromatic ligand, a prototypical property of transition metals, brings out new metallomimetic properties of boron.

LncUBE2R2-AS1 acts as a microRNA sponge of miR-302b to promote HCC progression via activation EGFR-PI3K-AKT signaling pathway.

Hepatocellular carcinoma (HCC) is a main cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) play important roles in diverse cancers. LncRNA-UBE2R2-AS1 has been reported to promote apoptosis in glioma cell. However, the expressions, functions, and mechanisms of action of UBE2R2-AS1 in HCC are still unclear. UBE2R2-AS1 is increased in HCC tissues and cell lines. Increased expression of UBE2R2-AS1 is associated with large tumor size, multiple tumor number, advanced TNM stage, and poor survival of HCC patients. Functional experiments showed that knockdown UBE2R2-AS1 inhibited HCC growth and metastasis through in vitro and in vivo experiments. Regarding the mechanism, UBE2R2-AS1/miR-302b/EGFR established the ceRNA network involved in the modulation of cell progression of HCC cells via activation of PI3K-AKT signaling pathway. Overall, UBE2R2-AS1 may exhibit an oncogenic function in HCC via acting as a sponge for miR-302b to up-regulate EGFR, and may serve as a potential therapeutic target and a prognostic biomarker for HCC patients.

Effects of water exchange rate on morphological and physiological characteristics of two submerged macrophytes from Erhai Lake.

Growth patterns of aquatic macrophytes have been shown to vary in response to hydrological properties; however, such properties are typically characterized by water level fluctuation, flow velocity, flooding season, and sedimentation, but not by water exchange rate (WER). Herein, we experimentally investigated how WER (three levels: exchange 0%, 20%, and 40% of total water per day) affects water and sediment properties, and the consequences that these variations have on the individual responses of two submerged macrophytes, Hydrilla verticillata and Myriophyllum aquaticum which were planted in two different sediment types (sand and clay). In the experiment without ramets, it was found that turbidity, pH value, and dissolved carbon dioxide concentration of the system water were statistically unaffected by WER, while water dissolved oxygen (DO) concentration and sediment oxidation-reduction potential (ORP, in both sediments) consistently increased with increasing WER, regardless of experimental time. In the experiment containing ramets, biomass accumulation and relative growth rate (RGR) of both species gradually increased with increasing WER regardless of sediment type. The mechanisms were related to (a) increased oxygen availability, as indicated by gradually increased water DO concentration and sediment ORP; and (b) enhanced phosphorus (P) and nitrogen (N) absorbing abilities associated with stimulated root growth, reflected in increased mean root length, specific root length, and the root/above-ground biomass ratio, with increasing WER. Additionally, in the experiments containing ramets, significant linear relationships were consistently detected between sediment ORP and root parameters, root parameters and plant nutrients (N and P), and plant nutrients and plant growth conditions (biomass accumulation and RGR). These results demonstrate that WER plays an important role in determining oxygen availability and thus impacts the growth of submerged macrophytes by altering the ability of roots to absorb nutrients, indicating that ecosystem functions are more sensitive to WER than previously recognized.