ABSTRACT
Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.
Subject(s)
Diarrhea Virus 1, Bovine Viral , Diarrhea Viruses, Bovine Viral , Cattle , Animals , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Diarrhea Viruses, Bovine Viral/physiology , CD8-Positive T-Lymphocytes , Fatty Acids , LipidsABSTRACT
Due to the elusive nature of polyoxometallates (POMs) in the assembly of silver clusters, POMs trapped by silver clusters are usually different from the pristine form, which surely increases the novelty of the assembly results but makes the final structure predictability challenging. Herein, three novel high-nuclearity silver-thiolate clusters trapping two kinds of classical POMs, Lindqvist-Mo6O192- and V10O286-, are reported. They are identified to be [(V10O28)@Ag44] (SD/Ag44a), [(V10O28)@Ag46] (SD/Ag46), and [(Mo6O19)@Ag44] (SD/Ag44b) clusters, which are further extended to 1D chain, 2D sql layer, and 3D pcu framework, respectively. Of note, SD/Ag44b contains a regular cubic Mo6O19 core sealed by an Ag44(EtS)24 shell in a pseudo-sodalite unit and six SCl4 planar squares connecting the respective adjacent silver tetragonal faces. This structure is a novel zeolite closely related to the natural alumino-silicate 'sodalite' but exceptionally made of core-shell silver clusters. Moreover, the Oh symmetric Mo6O192- templates an Oh symmetric Ag44 cluster in SD/Ag44b, realizing authentic symmetry delivery from guest to host in this system. This is a rare silver cluster family with classical POMs encapsulated.
ABSTRACT
Polymer materials exhibit unique properties in the fabrication of optical waveguide devices, electromagnetic devices, and bio-devices. Direct laser writing (DLW) technology is widely used for micro-structure fabrication due to its high processing precision, low cost, and no need for mask exposure. This paper reviews the latest research progresses of polymer-based micro/nano-devices fabricated using the DLW technique as well as their applications. In order to realize various device structures and functions, different manufacture parameters of DLW systems are adopted, which are also investigated in this work. The flexible use of the DLW process in various polymer-based microstructures, including optical, electronic, magnetic, and biomedical devices are reviewed together with their applications. In addition, polymer materials which are developed with unique properties for the use of DLW technology are also discussed.
ABSTRACT
Polymers are promising materials for fabricating photonic integrated waveguide devices. Versatile functional devices can be manufactured using a simple process, with low cost and potential mass-manufacturing. This paper reviews the recent progress of polymer photonic integrated devices fabricated using the UV imprinting technique. The passive polymer waveguide devices for wavelength filtering, power splitting, and light collecting, and the active polymer waveguide devices based on the thermal-optic tuning effect, are introduced. Then, the electro-optic (EO) modulators, by virtue of the high EO coefficient of polymers, are described. Finally, the photonic biosensors, which are based on low-cost and biocompatible polymer platforms, are presented.