Proximal spinal muscular atrophy (SMA) is a motor neuron degeneration disorder for which there is currently no effective treatment. Here, we report three compounds (sodium vanadate, trichostatin A and aclarubicin) that effectively enhance SMN2 expression by inducing Stat5 activation in SMA-like mouse embryonic fibroblasts and human SMN2-transfected NSC34 cells. We found that Stat5 activation enhanced SMN2 promoter activity with increase in both full-length and deletion exon 7 SMN transcripts in SMN2-NSC34 cells. Knockdown of Stat5 expression disrupted the effects of sodium vanadate on SMN2 activation but did not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2 transcriptional regulation. In addition, constitutive activation of Stat5 mutant (Stat5A1*6) profoundly increased the number of nuclear gems in SMA-patient lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. These results demonstrate that Stat5 signaling could be a possible pharmacological target for treating SMA.
Fatty liver diseases, common metabolic diseases in chickens, can lead to a decrease in egg production and sudden death of chickens. To solve problems caused by the diseases, reliable chicken models of fatty liver disease are required. To generate chicken models of fatty liver, 7-week-old ISA female chickens were fed with a control diet (17% protein, 5.3% fat, and 1,300 mg/kg choline), a low protein and high fat diet ( LPHF , 13% protein, 9.1% fat, and 1,300 mg/kg choline), a high cholesterol with low choline diet ( CLC , 17% protein, 7.6% fat with additional 2% cholesterol, and 800 mg/kg choline), a low protein, high fat, high cholesterol, and low choline diet ( LPHFCLC , 13% protein, 12.6% fat with additional 2% cholesterol, and 800 mg/kg choline) for 4 wk. Our data showed that the CLC and LPHFCLC diets induced hyperlipidemia. Histological examination and the content of hepatic lipids indicated that the CLC and LPHFCLC diets induced hepatic steatosis. Plasma dipeptidyl peptidase 4, a biomarker of fatty liver diseases in laying hens, increased in chickens fed with the CLC or LPHFCLC diets. Hepatic ballooning and immune infiltration were observed in these livers accompanied by elevated interleukin 1 beta and lipopolysaccharide induced tumor necrosis factor mRNAs suggesting that the CLC and LPHFCLC diets also caused steatohepatitis in these livers. These diets also induced hepatic steatosis in Plymouth Rock chickens. Thus, the CLC and LPHFCLC diets can be used to generate models for fatty liver diseases in different strains of chickens. In ISA chickens fed with the CLC diet, peroxisome proliferator-activated receptor γ, sterol regulatory element binding transcription factor 1, and fatty acid synthase mRNAs increased in the livers, suggesting that lipogenesis was enhanced by the CLC treatment. Our data show that treatment with CLC or LPHFCLC for 4 wk induces fatty liver disease in chickens. These diets can be utilized to rapidly generate chicken models for fatty liver research.
Alternative growth promoters are able to not only effectively replace the traditional use of antibiotics but also provide additional health benefits for livestock and reduce food safety concerns. This study investigated the effects of dry Hydrastis canadensis on the laying performance and fecal microbial community of laying hens. Twenty-four Lohmann (LSL, white layer strain) hens were reared from 40 to 48 weeks of age and randomly allotted to four dietary treatments (six birds/treatment). The dietary treatments comprised a basal diet with no treatment as control, a basal diet plus 0.6% powder of dry Hydrastis canadensis roots (R) or leaves (L), and a basal diet plus 0.6% powder of a mixture of dry Hydrastis canadensis roots and leaves (1:1, LR). No mortality was observed in the whole experimental period. The results indicated that albumen height in the LR group was significantly greater than that in the control group. The diet supplemented with Hydrastis canadensis had no significant effects on egg production rate, egg weight, eggshell strength, eggshell thickness, Haugh unit, or yolk height during the whole experimental phase. However, principal coordinate analysis, comparative heat map analysis, and cluster dendrogram analysis of cecal microbiota showed distinct clusters among the groups treated with Hydrastis canadensis and the control group. Regarding blood biochemical parameters, serum cholesterol levels were significantly lower in all Hydrastis canadensis-treated groups compared with those in the control group. Moreover, serum low-density lipoprotein levels were lower in hens supplemented with the leaf of Hydrastis canadensis. The abundances of the phyla Fusobacteria and Kiritimatiellaeota were increased (p < 0.05) in laying hens fed with 0.6% Hydrastis canadensis leaves, whereas the abundance of the phylum Firmicutes in cecum digesta decreased in response to treatment with Hydrastis canadensis roots and leaves. The relative abundance of the Fusobacterium genus was higher in the LR group compared with that in the control. On the contrary, we found a different trend in the Synergistes genus. The potential influences of these microbiota on the performance of laying hens were discussed. The results demonstrate that Hydrastis canadensis can improve the egg albumen height and modulate the cecum digesta microbiota composition of laying hens.
Fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disease in birds. FLHS have highly incidence rate in cage system. The syndrome can be characterized by abnormal lipid accumulation in liver which trigger inflammation and hemorrhage syndrome. Moreover, FLHS decrease egg production severely and have huge impact to the poultry industry. Additionally, FLHS is similar diagnosis to non‐alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of liver disorders and characterized by excessive hepatic fat accumulation. Ganoderma lucidum (G. lucidum) is a medicinal mushroom. G. lucidum is rich in bioactive components comprises and has hepatoprotective activity. Dipeptidyl‐peptidase 4 (DPP4) is a type II transmembrane protein and strongly associated with FLHS and NAFLD. The objective of this study was to determine the effects of feeding diets containing different ratio of G. lucidum on FLHS and the association of plasma DPP4 in hens and to use LMH cell to study the role of DPP4 in FLHS. Thirty 7‐week‐old, ISA hens were allotted to 5 treatments with 6 hens per replicate and fed high cholesterol low choline (CLC), CLC + 0.25% G. lucidum, CLC + 0.5% G. lucidum, CLC + 0.75% G. lucidum, and CLC + 1% G. lucidum, respectively, for six weeks. Body weight and plasma were recorded every three week. At the end of experiment, livers were photographed, excised, weighed, and scored for liver hemorrhages. The results showed that CLC + 1% G. lucidum body weight was significantly higher than CLC + 0.25% G. lucidum and treatment of G. lucidum decreased the level of triglyceride in the plasma. Oleic acid induced DPP4 mRNA expression in LMH cells, suggesting that there is an association between lipid and DPP4 expression in the liver cell. In conclusion, G. lucidum could be a dietary additive or medicine for reducing fatty liver in laying hens.
In this paper, two types of 458-chamfers are embedded to an L-shape (908-bent) hollow waveguide which is formed by omni-directional reflector to improve the transmission efficiency. Compared with that of an abrupt 908-bent hollow waveguide, the proposed structures have enhanced the transmission efficiency by a factor of more than 4. The design rules of the 458-chamfer and the fabrication considerations are discussed in detail.
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