Current knowledge about the relationships between ruminal bacterial communities and metabolite profiles in the yak rumen is limited. This is due to differences in the nutritional and metabolic features between yak and other ordinary cattle combined with difficulties associated with farm-based research and a lack of technical guidance. A comprehensive analysis of the composition and alterations in ruminal metabolites is required to advance the development of modern yak husbandry. In the current study, we characterized the effect of feed type on the ruminal fluid microbiota and metabolites in yak using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). Bacteroidetes and Firmicutes were the predominant bacterial phyla in the yak rumen. At the genus level, the relative abundance of Bacteroidales BS11 gut group, Prevotellaceae UCG-003, Ruminococcaceae UCG-011, Bacteroidales RF16 group and Ruminococcaceae UCG-010 was significantly ( P < 0.01) higher in the forage group compared to that in the concentrate group, while the concentrate group harbored higher proportions of Bacteroidales S24-7 group, Ruminococcaceae NK4A214, Succiniclasticum and Ruminococcus 2 . Yak rumen metabolomics analysis combined with enrichment analysis revealed that feed type altered the concentrations of ruminal metabolites as well as the metabolic pattern, and significantly ( P < 0.01) affected the concentrations of ruminal metabolites involved in protein digestion and absorption (e.g., L-arginine, ornithine, L-threonine, L-proline and β-alanine), purine metabolism (e.g., xanthine, hypoxanthine, deoxyadenosine and deoxyadenosine monophosphate) and fatty acid biosynthesis (e.g., stearic acid, myristic acid and arachidonic acid). Correlation analysis of the association of microorganisms with metabolite features provides us with a comprehensive understanding of the composition and function of microbial communities. Associations between utilization or production were widely identified between affected microbiota and certain metabolites, and these findings will contribute to the direction of future research in yak.

Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. Long chain acyl-CoA synthetase 4 (ACSL4), an enzyme has pivotal roles in arachidonic acid (AA) metabolism. However, its function and the underlying molecular mechanisms in HCC are still not fully elucidated. Here, we identified ACSL4 as a novel marker for AFP high subtype HCC through transcriptome profiling. ACSL4 was frequently upregulated in HCC samples and associated with poor prognosis. Functionally, ACSL4 knockdown resulted in decreased cell growth, whereas ectopic ACSL4 expression facilitated tumor formation in vitro and in vivo. Mechanistically, ACSL4 stabilized the oncoprotein c-Myc through ubiquitin-proteasome system in an ERK/FBW7-dependent manner. Cell growth ability mediated by ACSL4 elevation was partly attenuated by c-Myc depletion using siRNA or its inhibitor 10058-F4. In contrast, the effects of ACSL4 silencing were partially reversed by c-Myc overexpression via FBW7 knockdown. Clinically, ACSL4 expression was positively correlated with c-Myc in HCC. In conclusion, ACSL4 is a novel marker for AFP high subtype HCC. Our data uncovered a new mechanism by which ACSL4 promotes HCC progression via c-Myc stability mediated by ERK/ FBW7/c-Myc axis and could be a valuable prognostic biomarker and a potential therapeutic target in HCC.

Positron-emission tomography (PET) is routinely used in the clinic for tumor imaging with ultrahigh sensitivity, but tumor-targeted PET imaging probes are quite few. In this work, we rationally designed a furin-responsive radiotracer Acetyl-Arg-Val-Arg-Arg-Cys­(StBu)-Lys­(DOTA-68Ga)-CBT (CBT- 68 Ga) and demonstrated that coinjection of the radiotracer with its cold analogue CBT-Ga instructed the formation of 68Ga nanoparticles in furin-overexpressing MDA-MB-468 cancer cells, which significantly enhanced microPET imaging of the tumor in vivo. In vitro results showed that CBT-Ga subjected to furin-initiated CBT-Cys condensation reaction and self-assembly to form the nanoparticles CBT-Ga-NPs with an average diameter of 258.3 nm. In vivo microPET imaging results indicate that the mice coinjected with CBT- 68 Ga and CBT-Ga, which warrants 68Ga nanoparticle formation in their MDA-MB-468 tumors, had a tumor/liver ratio 9.1-fold of that of the mice only injected with CBT- 68 Ga. We envisioned that, by replacing the RVRR substrate of CBT- 68 Ga with other enzyme-specific ones and using the strategy of intracellular nanoparticle formation, a series of radioactive probes could be developed for more sensitive and precise tumor microPET imaging in the near future.

Positron-emission tomography (PET) imaging enables cancer diagnosis at an early stage and to determine its pathological degree. However, tumor uptake efficiency of traditional PET radiotracers is usually low. Herein, we rationally designed a precursor CBT-NODA, the cold analogue CBT-NODA-Ga, and its corresponding radiotracer CBT-NODA-68Ga. Using these three compounds, we verified that coinjection of CBT-NODA-68Ga with CBT-NODA or CBT-NODA-Ga could lead to the synthesis of hybrid gallium-68 nanoparticles in furin-overexpressing cancer cells and enhance microPET tumor imaging in mice. In vivo experiments showed that coinjection of CBT-NODA-68Ga with CBT-NODA-Ga had the most prolonged retention of the radiotracer in blood, the highest radioactivity in tumor regions, and the most enhanced microPET tumor imaging in mice. We anticipate that, by combining the coinjection strategy with our CBT-Cys click condensation reaction, more radiotracers are developed for microPET imaging of more tumors in clinical settings in the future.

No abstract

The aim of this study was to investigate the effects of graded levels of montmorillonite, a constituent of clay, on performance, hematological parameters and bone mineralization in weaned pigs. One hundred and twenty, 35-d-old crossbred pigs (Duroc×Large White×Landrace, 10.50±1.20 kg) were used in a 28-d experiment and fed either an unsupplemented corn-soybean meal basal diet or similar diets supplemented with 0.5, 1.0, 2.5 or 5.0% montmorillonite added at the expense of wheat bran. Each treatment was replicated six times with four pigs (two barrows and two gilts) per replicate. Feed intake declined (linear and quadratic effect, p< 0.01) with increasing level of montmorillonite while feed conversion was improved (linear and quadratic effect, p<0.01). Daily gain was unaffected by dietary treatment. Plasma myeloperoxidase declined linearly (p = 0.03) with increasing dietary level of montmorillonite. Plasma malondialdehyde and nitric oxide levels were quadratically affected (p<0.01) by montmorillonite with increases observed for pigs fed the 0.5 and 1.0% levels which then declined for pigs fed the 2.5 and 5.0% treatments. In bone, the content of potassium, sodium, copper, iron, manganese and magnesium were decreased (linear and quadratic effect, p<0.01) in response to an increase of dietary montmorillonite. These results suggest that dietary inclusion of montmorillonite at levels as high as 5.0% does not result in overt toxicity but could induce potential oxidative damage and reduce bone mineralization in pigs.

No abstract

This study systematically evaluated the effect of ferric iron on sulfate reduction to sulfide, feed digestion and fermentation, methane production, and populations of select ruminal microbes using in vitro rumen cultures. Ferric oxide (Fe2O3) and ferric citrate (C6H5FeO7) at six concentrations (0, 25, 50, 100, 150, and 200mg/L as Fe(3+)) were tested. Ferric iron decreased production of both H2S gas in culture headspace (up to 71.9%) and aqueous sulfide (up to 80.8%), without adversely affecting other fermentation parameters, with ferric citrate being more effective than ferric oxide. Total archaeal population was increased by ferric citrate, but methane production was not affected significantly. The population of sulfate reducing bacteria was affected differently by ferric oxide than by ferric citrate. The results of this study could guide future in vivo studies to develop effective solutions to abate sulfur-associated polioencephalomalacia in cattle fed high-sulfur diet such as dried distiller's grains with solubles.