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Staphylococcus aureus (S. aureus) is a major mastitis-causing pathogen in dairy cows. Dairy cows with mastitis suffer from a decrease in milk yield and protein content. Chlorogenic acid (CGA) is a natural product with anti-inflammatory effects. In this study, we examined the function and mechanism of CGA with regard to its anti-inflammatory effects and evaluated its protective function in milk protein synthesis in bovine mammary epithelial cells (BMECs). BMECs were cultured with and without infection by S. aureus and CGA, and extracellular inflammatory cytokines and amino acids in the medium and milk proteins were determined by ELISA. The function of IL-10RA in anti-inflammatory processes and of SF-1 in milk protein synthesis was assessed by gene silencing. The activity of mTORC1, NF-κB, and STAT5 was examined by western blot. S. aureus caused intracellular infection and upregulated TNF-α, IL-1ß, IL-6, and IL-8, whereas uptake of amino acids and milk protein synthesis were suppressed. CGA mitigated the S. aureus-induced inflammatory response and milk protein synthesis in vitro and in vivo. CGA alleviated S. aureus-induced inhibition of mTORC1 and STAT5 and upregulated IL-10 and IL-10RA. In addition, SF-1 was predicted to be a transcription factor of the milk protein-encoding genes α-LA, ß-LG, and CSN2. S. aureus downregulated SF-1 and CGA reversed the decline in milk protein synthesis due to SF-1 knockdown. Thus, CGA mitigates the inflammatory response that is induced by S. aureus and protects the uptake of amino acids and milk protein synthesis in BMECs.
Assuntos
Ácido Clorogênico , Mastite Bovina , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Anti-Inflamatórios/farmacologia , Bovinos , Ácido Clorogênico/farmacologia , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas do Leite/metabolismo , Fator de Transcrição STAT5 , Infecções Estafilocócicas/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This work reports an experiment/simulation combination study on the magnetorheological (MR) mechanism of magnetic fluid based on Fe3O4 hollow chains. The decrease of shear stress versus the increasing magnetic field was observed in a dilute magnetic fluid. Hollow chains exhibited a higher MR effect than pure Fe3O4 hollow nanospheres under a small magnetic field. A modified particle level simulation method including the translational and rotational motion of chains was developed to comprehend the correlation between rheological properties and microstructures. Sloping cluster-like microstructures were formed under a weak external field (24 mT), while vertical column-like microstructures were observed under a strong field (240 mT). The decrease of shear stress was due to the strong reconstruction process of microstructures and the agglomeration of chains near the boundaries. The chain morphology increased the dip angle of microstructures and thus improved the MR effect under a weak field. This advantage made Fe3O4 hollow chains to be widely applied for small and low-power devices in the biomedical field. Dimensionless viscosity as a function of the Mason number was collapsed onto linear master curves. Magnetic fluid in Poiseuille flow in a microfluidic channel was also observed and simulated. A qualitative and quantitative correspondence between simulations and experiments was obtained.
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A novel S-ST/MWCNT/Kevlar-based wearable electronic textile (WET) with enhanced safeguarding performance and force sensing ability was fabricated. Stab resistance performance tests under quasi-static and dynamic conditions show that the maximum resistance force and penetration impact energy for the WET are 18 N and 11.76 J, which represent a 90% and 50% increment with respect to the neat Kevlar, respectively. Dynamic impact resistance tests show that the WET absorbs all the impact energy. The maximum resistance force of the WET is 1052 N, which represents an improvement of about 190% with respect to neat Kevlar. With the incorporation of multi-walled carbon nanotubes (MWCNTs), the WET can achieve a stable electrical conductivity of â¼10-2 S m-1, and the conductivity is highly sensitive to external mechanic forces. Notably, the sensing fabric also exhibits an outstanding ability to detect and analyze external forces. In addition, it can be fixed at any position of the human body and exhibits an ideal monitoring performance. Because of its flexibility, high sensitivity to various types of deformations and excellent safeguarding performance, the WET has a strong potential for wearable monitoring devices that simultaneously provide body protection and monitor the movements of the human body under various conditions.
RESUMO
Stearic acid (C18:0, SA) is a saturated long-chain fatty acid (LCFA) that has a prominent function in lactating dairy cows. It is obtained primarily from the diet and is stored in the form of triacylglycerol (TAG) molecules. The transmembrane glycoprotein cluster of differentiation 36 (CD36) is also known as fatty acid translocase, but whether SA promotes lipid synthesis through CD36 and FAK/mTORC1 signaling is unknown. In this study, we examined the function and mechanism of CD36-mediated SA-induced lipid synthesis in bovine mammary epithelial cells (BMECs). SA-enriched supplements enhanced lipid synthesis and the FAK/mTORC1 pathway in BMECs. SA-induced lipid synthesis, FAK/mTORC1 signaling, and the expression of lipogenic genes were impaired by anti-CD36 and the CD36-specific inhibitor SSO, whereas overexpression of CD36 effected the opposite results. Inhibition of FAK/mTORC1 by TAE226/Rapamycin attenuated SA-induced TAG synthesis, inactivated FAK/mTORC1 signaling, and downregulated the lipogenic genes PPARG, CD36, ACSL1, SCD, GPAT4, LIPIN1, and DGAT1 at the mRNA and protein levels in BMECs. By coimmunoprecipitation and yeast two-hybrid screen, CD36 interacted directly with Fyn but not Lyn, and Fyn bound directly to FAK; FAK also interacted directly with TSC2. CD36 linked FAK through Fyn, and FAK coupled mTORC1 through TSC2 to form the CD36/Fyn/FAK/mTORC1 signaling axis. Thus, stearic acid promotes lipogenesis through CD36 and Fyn/FAK/mTORC1 signaling in BMECs. Our findings provide novel insights into the underlying molecular mechanisms by which LCFA supplements promote lipid synthesis in BMECs.
Assuntos
Lactação , Lipogênese , Feminino , Bovinos , Animais , Lipogênese/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Glândulas Mamárias Animais/metabolismo , Ácidos Esteáricos/farmacologia , Ácidos Graxos/metabolismo , Células Epiteliais/metabolismoRESUMO
Chlorogenic acid (CGA) as one of the most ubiquitously dietary polyphenolic compounds, has been reported to have various antimicrobial effects and exhibit strong anti-inflammatory ability. Staphylococcus aureus is a gram-positive bacterium that can induce mastitis. However, the mechanism through which S. aureus infection affects lipid synthesis and whether CGA have protective effect on S. aureus reduced lipid synthesis is not fully understood. In this study, the internalization of S. aureus reduced intracellular lipid droplet formation, decreased the levels of intracellular triacylglycerol, total cholesterol and 7 types of fatty acid and downregulated the expression of lipogenic genes FAS, ACC, and DGAT1 in bovine mammary epithelial cells (BMECs). In addition, we found that S. aureus intracellular infection attenuated mTORC1 activation resulting in Lipin 1 nuclear localization. Remarkablely, S. aureus infection-mediated repression of lipid synthesis related to the mTORC1 signaling and Lipin 1 nuclear localization can be alleviated by CGA. Thus, our findings provide a novel mechanism by which lipid synthesis is regulated under S. aureus infection and the protective effects of CGA on lipid synthesis in BMECs.
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In addition to serving as the building blocks for protein synthesis, amino acids serve as critical signaling molecules in cells. However, the mechanism through which amino acid signals are sensed in cells is not yet fully understood. This study examined differences in the phosphorylation levels of proteins in response to amino acid signals in Cashmere goat fetal fibroblasts (GFb). Amino acid deficiency was found to induce autophagy and attenuate mammalian/mechanistic target of rapamycin complex (mTORC1)/Unc-51-like autophagy activating kinase 1 (ULK1) signaling in GFb cells. A total of 144 phosphosites on 102 proteins positively associated with amino acid signaling were screened using phosphorylation-based proteomics analysis. The mitogen-activated protein kinase (MAPK) signaling pathway was found to play a potentially important role in the interaction network involved in the response to amino acid signals, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and MAPK1/3 may serve as a central hub for the entire network. Motif analysis identified three master motifs, xxx_S_Pxx, xxx_S_xxE, and xxx_S_xDx, which were centered on those phosphosites at which phosphorylation was positively regulated by amino acid signaling. Additionally, the phosphorylation levels of three membrane proteins, the zinc transporter SLC39A7, the sodium-dependent neutral amino acid transporters SLC1A5 and SLC38A7, and three translation initiation factors, eukaryotic initiation factor (eIF)5B, eIF4G, and eIF3C, were positively regulated by amino acid signals. These pivotal proteins were added to currently known signaling pathways to generate a novel model of the network pathways associated with amino acid signals. Finally, the phosphorylation levels of threonine 203 and tyrosine 205 on MAPK3 in response to amino acid signals were examined by western blot analysis, and the results were consistent with the data from the phosphoproteomics analysis. The findings of this study provide new evidence and insights into the precise mechanism through which amino acid signals are sensed and conducted in Cashmere goat fetal fibroblasts.
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This work reported a facile method for fabricating multi-layered polydopamine (PDA) encapsulated AuAg@C@AuAg core/shell nanosphere with a hollow interior. During the synthetic process, the preliminary Ag@C nanosphere is easily covered by an AuAg/PDA hybrid layer through the in situ redox-oxidized polymerization to form the Ag-AuAg@C@AuAg/PDA precursor, in which the AuAg bimetallic nanocrystals are simultaneously obtained via the electrochemical substitution reaction. After etching the residue Ag core, the final AuAg@C@AuAg/PDA hybrid nanosphere is achieved and the inner AuAg shows a unique nanoframe-like nanostructure. The carbon shell plays an important role for the formation and structure evolution of the AuAg@C@AuAg/PDA, and the composition can be modulated by varying the polymerization process. Owing to the well distributed AuAg nanocrystals and inner AuAg nanoframes, the AuAg@C@AuAg/PDA shows better performance than Ag-AuAg@C@AuAg/PDA precursor in catalyzing 4-nitrophenol, and the rate constant (K) to catalyst weight ratio reaches as high as 3.63 min-1 â¢mg-1. As a result, this work not only offers a hybrid bi-metallic nanocatalyst with excellent performance, but also has valuable implications for compositional modulation of hollow interior multi-layered nanostructure in adsorption, drug delivery, and nanocatalysis.
RESUMO
With the rapid development of the electronics, information technology, and wearable devices, problems of the power crisis and electromagnetic radiation pollution have emerged. A piezoelectric wearable textile combined with electromagnetic shielding performance has become a favorable solution. Herein, a multifunctional PVDF-based wearable sensor with both electromagnetic shielding function and human body monitoring performance is proposed by incorporating silver nanowires (Ag NWs) and multiwall carbon nanotubes (MWCNTs) hybrid-networks into PVDF-casted commercial nonwoven fabrics (NWF). The coordination of Ag NWs and MWCNTs networks ensures the ideal electrical conductivity and mechanical strength. The maximum shielding value of the developed sensor reaches up to 34 dB when the area densities of the Ag NWs and MWCNT are kept at 1.9 and 2.0 mg/cm2, respectively. Additionally, the hydrophobicity of the as-proposed sensor (water contact angle of â¼110.0°) ensures the self-cleaning function and makes it resistive against water and dirt. Moreover, the sensor possesses a force-sensing property by generating different piezoelectric voltages (0, 0.4, 1.0, and 1.5 V) when stimulated by various forces (0, 20, 44, and 60 N). Not only can it respond to different external stress in a timely manner (response sensitivity of â¼0.024 V/N, response time of â¼35 ms), but it can also monitor different body movements, such as joint bending, running, and jumping. This work opens up a new prospect of monitoring the human body as well as protecting human health from electromagnetic radiation surroundings.
Assuntos
Monitorização Fisiológica/métodos , Nanofios/química , Têxteis , Dispositivos Eletrônicos Vestíveis , Campos Eletromagnéticos/efeitos adversos , Fenômenos Eletromagnéticos , Corpo Humano , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanotubos de Carbono/química , Polivinil/química , Prata/química , Água/químicaRESUMO
This work reports a facile one-step method for the fabricating Fe3O4@Au/polydopamine sandwich-like core-shell nanostructure, in which the Au/polydopamine (Au/PDA) hybrid shell is obtained via an in situ redox-oxidation polymerization between the HAuCl4 and dopamine. The content of Au nanocrystals, shell thickness, and particle sizes are tunable by varying the experimental parameters. Intriguingly, this general method can be applied for different functional nanostructures such as the ß-FeOOH@Au/PDA, SiO2@Au/PDA, and CNT@Au/PDA nanocomposites. A possible formation mechanism is proposed and it is found that the surface interaction plays a key role in determining the final nanostructure. The as-prepared Fe3O4@Au/PDA exhibited eminent catalytic activity on the reduction of 4-nitrophenol. Since the external PDA shell prevents the Au nanocrystals from leaching during the reduction, the cycling activity has been maintained as high as 95% after seven times of catalytic reaction.
RESUMO
A simple and scalable "dip and dry" method was developed for fabricating stretchable polyurethane sponge-based polymer composite with excellent shear stiffening effect, creep resisting and adhesion property. The stiffness of the composite was tunable, the storage modulus (G') could automatically increase 3 orders of magnitude with the increasing of shear frequency, and the G'max could reach to as high as 1.55 MPa. Importantly, the composite with ideal damping capacity reduced the impact force by 2 orders of magnitude even under 26 cycles of consecutive dynamic impact loading with no obvious mechanical degradation. Moreover, an enhancing mechanism was proposed and it was found the "B-O cross bond" and the entanglement of polymer chains were attributed to the shear stiffening characteristic. Finally, the excellent adhesion ability and hydrophobicity guarantee the composite with reliable mechanical performance and longer lifespan.