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Endothelial cell senescence is the main risk factor contributing to vascular dysfunction and the progression of aging-related cardiovascular diseases. However, the relationship between endothelial cell metabolism and endothelial senescence remains unclear. The present study provides novel insight into fatty acid metabolism in the regulation of endothelial senescence. In the replicative senescence model and H2O2-induced premature senescence model of primary cultured human umbilical vein endothelial cells (HUVECs), fatty acid oxidation (FAO) was suppressed and fatty acid profile was disturbed, accompanied by downregulation of proteins associated with fatty acid uptake and mitochondrial entry, in particular the FAO rate-limiting enzyme carnitine palmitoyl transferase 1A (CPT1A). Impairment of fatty acid metabolism by silencing CPT1A or CPT1A inhibitor etomoxir facilitated the development of endothelial senescence, as implied by the increase of p53, p21, and senescence-associated β-galactosidase, as well as the decrease of EdU-positive proliferating cells. In the contrary, rescue of FAO by overexpression of CPT1A or supplement of short chain fatty acids (SCFAs) acetate and propionate ameliorated endothelial senescence. In vivo, treatment of acetate for 4 weeks lowered the blood pressure and alleviated the senescence-related phenotypes in aortas of Ang II-infused mice. Mechanistically, fatty acid metabolism regulates endothelial senescence via acetyl-coenzyme A (acetyl-CoA), as implied by the observations that suppression of acetyl-CoA production using the inhibitor of ATP citrate lyase NDI-091143 accelerated senescence of HUVECs and that supplementation of acetyl-CoA prevented H2O2-induced endothelial senescence. Deficiency of acetyl-CoA resulted in alteration of acetylated protein profiles which are associated with cell metabolism and cell cycle. These findings thus suggest that improvement of fatty acid metabolism might ameliorate endothelial senescence-associated cardiovascular diseases.

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Seven yeast strains were isolated from the gut of insect larvae and decayed wood, which were collected from three localities near Nanyang, Henan Province, China. These strains were identified as two novel species through comparison of sequences in the D1/D2 domains of the large subunit (LSU) rRNA gene and other taxonomic characteristics. Pichia dushanensis sp. nov. was closely related to species in the Pichia clade and produced one to four spheroid ascospores in a deliquescent ascus. The D1/D2 sequence of P. dushanensis sp. nov. differed from its closest relative, Issatchenkia (Pichia) sp. NRRL Y-12824, by 3.6 % sequence divergence (16 substitutions and 4 gaps). The species also differed from its four closest known species, Candida rugopelliculosa, Pichia occidentalis, Pichia exigua and Candida phayaonensis, by 4.1–4.4 % sequence divergence (22–24 substitutions and 0–2 gaps) in the D1/D2 sequences. Hyphopichia paragotoi sp. nov. belonged to the Hyphopichia clade, and its nearest phylogenetic neighbours were Candida gotoi, Candida pseudorhagii, Candida rhagii and Hyphopichia heimii with 3.2–4.2 % sequence divergence (16–21substitutions and 1 gap) in the D1/D2 sequences. In comparison with previously established species, H. paragotoi sp. nov. formed one hat-shaped ascospore in a persistent ascus. The type strain of P. dushanensis sp. nov. is NYNU 14658T ( = CICC 33049T = CBS 13912T), and the type strain of H. paragotoi sp. nov. is NYNU 14666T ( = CICC 33048T = CBS 13913T).

Mucosal immunity is critical in preventing infectious bronchitis virus (IBV) infection. To deliver viral antigens to the mucosal immune system of chickens safely and effectively, we constructed a Lactococcus lactis strain carrying IBV multi-epitope gene EpiC fused with the gene of the cell-wall anchoring domain of Staphylococcus aureus protein A. SDS-PAGE and Western blot results indicated that the fused peptide was located partially on the cell surface. Oral and nasal inoculation with the recombinant L. lactis of chickens elicited significantly high humoral and mucosal immune responses, especially in the nasally immunized group. Eighty percent chickens of the nasally immunized group with recombinant L. lactis did not show any clinical signs after a lethal dose challenge with IBV SAIBk strain, while all the non-recombinant L. lactis immunized chickens exhibited obvious and typical symptoms. These results indicate that needle-free recombinant lactococci anchoring the IBV antigen makes a promising vaccine candidate against the spread of IB.

The avian infectious bronchitis virus (IBV) multi-epitope based peptide EpiC was found to be effective in inducing strong humoral and cellular responses against IBV. In this study, the gene EpiC was introduced into Lactococcus lactis NZ3900, and three recombinant strains expressing EpiC in intracellular and extracellular forms were constructed. SDS-PAGE and Western blot results indicated that EpiC was successfully expressed and had good immunoreactivity with chicken anti-IBV serum. Fusion of the signal pepitide gene SPusp45 and the nine-peptide LEISSTCDA encoding oligonucleotide to EpiC increased the secretion of EpiC, but reduced the total yields of EpiC. Oral immunization to specific-pathogen-free (SPF) chickens with recombinant strains induced significantly higher levels of humoral immune responses, and provided protection against lethal dose challenge by the IBV SAIBk strain. These results indicate that it is feasible to use L. lactis as an antigen delivery vehicle in developing oral vaccines against IBV infection.