Investigating the Short-Term Effects of Cold Stress on Metabolite Responses and Metabolic Pathways in Inner-Mongolia Sanhe Cattle

Inner-Mongolia Sanhe cattle are well-adapted to low-temperature conditions, but the metabolic mechanisms underlying their climatic resilience are still unknown. Based on the 1H Nuclear Magnetic Resonance platform, 41 metabolites were identified and quantified in the serum of 10 heifers under thermal neutrality (5 °C), and subsequent exposure to hyper-cold temperature (−32 °C) for 3 h. Subsequently, 28 metabolites were pre-filtrated, and they provided better performance in multivariate analysis than that of using 41 metabolites. This indicated the need for pre-filtering of the metabolome data in a paired experimental design. In response to the cold exposure challenge, 19 metabolites associated with cold stress response were identified, mainly enriched in “aminoacyl-tRNA biosynthesis” and “valine, leucine, and isoleucine degradation”. A further integration of metabolome and gene expression highlighted the functional roles of the DLD(dihydrolipoamide dehydrogenase), WARS (tryptophanyl-tRNA synthetase), and RARS(arginyl-tRNA synthetase) genes in metabolic pathways of valine and leucine. Furthermore, the essential regulations of SLC30A6 (solute carrier family 30 (zinc transporter), member 6) in metabolic transportation for propionate, acetate, valine, and leucine under severe cold exposure were observed. Our findings presented a comprehensive characterization of the serum metabolome of Inner-Mongolia Sanhe cattle, and contributed to a better understanding of the crucial roles of regulations in metabolites and metabolic pathways during cold stress events in cattle

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib

AbstractSorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC

Investigating the Short-Term Effects of Cold Stress on Metabolite Responses and Metabolic Pathways in Inner-Mongolia Sanhe Cattle

Inner-Mongolia Sanhe cattle are well-adapted to low-temperature conditions, but the metabolic mechanisms underlying their climatic resilience are still unknown. Based on the 1H Nuclear Magnetic Resonance platform, 41 metabolites were identified and quantified in the serum of 10 heifers under thermal neutrality (5 °C), and subsequent exposure to hyper-cold temperature (−32 °C) for 3 h. Subsequently, 28 metabolites were pre-filtrated, and they provided better performance in multivariate analysis than that of using 41 metabolites. This indicated the need for pre-filtering of the metabolome data in a paired experimental design. In response to the cold exposure challenge, 19 metabolites associated with cold stress response were identified, mainly enriched in “aminoacyl-tRNA biosynthesis” and “valine, leucine, and isoleucine degradation”. A further integration of metabolome and gene expression highlighted the functional roles of the DLD (dihydrolipoamide dehydrogenase), WARS (tryptophanyl-tRNA synthetase), and RARS (arginyl-tRNA synthetase) genes in metabolic pathways of valine and leucine. Furthermore, the essential regulations of SLC30A6 (solute carrier family 30 (zinc transporter), member 6) in metabolic transportation for propionate, acetate, valine, and leucine under severe cold exposure were observed. Our findings presented a comprehensive characterization of the serum metabolome of Inner-Mongolia Sanhe cattle, and contributed to a better understanding of the crucial roles of regulations in metabolites and metabolic pathways during cold stress events in cattle