Depletion of stearoyl-CoA desaturase(scd) leads to fatty liver disease and defective mating behavior in zebrafish

Stearyl coenzyme A desaturase(SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids.In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant(scd-/-) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry(GC-MS) showed that the scd-/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd-/ -mammals, the scd-/- zebrafish showed significantly increased fat accumulation in the whole body,especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis.Mechanistically, srebf1, a gene encoding a transcriptional activator related to adipogenesis,acc1 and acaca, genes involved in fatty acid synthesis, and dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd-/- mutants could be rescued by ubiquitous transgenic overexpression of scd. In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.

Antibacterial ability and cytocompatibility of Cu-incorporated Ni–Ti–O nanopores on NiTi alloy

Nearly equiatomic nickel–titanium(NiTi) alloy is an ideal implant biomaterial because of its shape memory effect, superelasticity, low elastic modulus as well as other desirable properties.However, it is prone to infection because of its poor antibacterial ability.The present work incorporated Cu into Ni–Ti–O nanopores(NP–Cu) anodically grown on the NiTi alloy to enhance its antibacterial ability, which was realized through electrodeposition.Our results show that incorporation of Cu(0.78 at%–2.37 at%)has little influence on the NP diameter, length and morphology.The release level of Cu ions is in line with loadage which may be responsible for the improved antibacterial ability of the NiTi alloy to combat possible bacterial infection in vivo.Meanwhile, the NP–Cu shows better cytocompatibility and even can promote proliferation of bone marrow mesenchymal stem cells(BMSCs),up-regulate collagen secretion and extracellular matrix mineralization when compared with Cu-free sample.Better antibacterial ability and cytocompatibility of the NP–Cu render them to be promising when serving as NiTi implant coatings.

Selective inhibition effects on cancer cells and bacteria of Ni–Ti–O nanoporous layers grown on biomedical NiTi alloy by anodization

Stents made of nearly equiatomic NiTi alloy are used to treat malignant obstruction caused by cancer,but prevention of re-obstruction after surgery is still a challenge because the bare stents possess poor anticancer and antibacterial properties to inhibit cancer/bacteria invasion.The present work aims at endowing the NiTi alloy with anticancer and antibacterial abilities by surface modification.Ni–Ti–O nanoporous layers with different thicknesses were prepared on NiTi by anodization,and biological experiments were conducted to evaluate the effects on gram-positive Staphylococcus aureus,human lung epithelial cancer cells(A549),as well as human endothelial cells(EA.hy926).The nanoporous layer with a thickness of 10.1 lm inhibits growth of cancer cells and kill bacteria but shows little adverse effects on normal cells.Such selectivity is related to the larger amount of Ni ions leached from the sample in the acidic microenvironment of cancer cells in comparison with normal cells.The Ni–Ti–O nanoporous layers are promising as coatings on NiTi stents to prevent re-obstruction after surgery.

Improving exposure of anodically ordered Ni-Ti-O and corrosion resistance and biological properties of NiTi alloys by substrate electropolishing

Although Ni-Ti-O nanopores(NPs) can be fabricated by anodization of mechanically polished NiTi alloys, the top disordered layer is difficult to remove thus hindering the functionality of the Ni-Ti-O NPs. In this work, an electropolishing(EP) pretreatment was performed on the NiTi substrate prior to anodization to thoroughly expose the NPs. Our results show that the EP pretreatment for 5 min perfectly removes the top disordered layer on the Ni-Ti-O NPs to expose the underlying NPs and consequently, the corrosion resistance and antibacterial ability are enhanced. The exposed NPs can elongate bone marrow mesenchymal stem cells, which may be responsible for the upregulated alkaline phosphatase activity, secretion of Type I collagen, and extracellular matrix mineralization. These results suggest that EP is a desirable pretreatment before anodization of the NiTi alloys because the irregular surface layer on the Ni-Ti-O NPs can be removed to enhance the corrosion resistance and biological functions.