Impact of different dietary regimens on the lipidomic profile of mare's milk.

Despite mare's milk being highly nutritious and beneficial to human health, the effects of different dietary regimens on the lipid profile of mare's milk remain to be completely understood. Herein we employed targeted multiple reaction monitoring-based lipidomics with ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry to compare the milk lipid profiles of mares fed: pasture grass (P), corn stover and concentrate (H), or cornsilage and concentrate (S). Overall, 461 lipids belonging to 17 subclasses were identified; 261 significantly different lipids were identified on applying the following criteria: false discovery rate-adjusted P < 0.05, variable importance in projection ≥ 1.0, and fold change ≥ 2.0 or ≤ 0.5. The number of significantly different lipids decreased in the order of P > S > H. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using differential lipids led to the identification of 34, 32, and 31 metabolic pathways on pairwise comparisons between the P and H, P and S, and S and H groups, respectively. The milk of mares in the P group showed significantly higher levels of specific lipids, including triacylglycerols, phosphatidylcholines, and phosphatidylserines, which are known to participate in polyunsaturated fatty acid and lipid digestion and absorption-related metabolic pathways. Altogether, our data provide comprehensive insights into the correlations between feeding systems and quality of mare's milk in terms of bioactive profile.

Metal-organic framework-derived nitrogen-doped carbon-confined CoSe2 anchored on multiwalled carbon nanotube networks as an anode for high-rate sodium-ion batteries.

Metal selenides, as potential alternative candidates for sodium storage, have promising applicability due to their high theoretical specific capacity. However, their huge volume change and sluggish electrode kinetics during sodium ion uptake and release processes can result in insufficient cycling life and inferior rate performance, hindering their practical application. Herein, nitrogen (N)-doped carbon-confined cobalt selenide anchored on multiwalled carbon nanotube networks (denoted as CoSe2@NC/MWCNTs) was designed and successfully built through a selenization process with ZIF-67 MOF as the template. The existence of the interconnected MWCNT network plays a crucial role in not only enhancing the electronic conductivity and ion/electron-transfer efficiency but also ensuring structural stability. Consequently, the optimized CoSe2@NC/MWCNTs composite delivers a high reversible capacity of 479.6 mA h g-1 at a current rate of 0.2 A g-1, accompanied by a 92.0% capacity retention over 100 cycles and a predominant rate performance of 227.4 mA h g-1 even under 20 A g-1 when examined as the anode in Na-ion batteries. Moreover, the kinetic behaviors were confirmed using CV profiles at various rates, as well as the galvanostatic intermittent titration technique (GITT) and electrochemical impedance spectroscopy (EIS). Besides, the HRTEM images clearly reveal the sodium-ion storage mechanism of the CoSe2 hybrid. These results make CoSe2@NC/MWCNTs a prospective anode material in advanced sodium-ion batteries.

Intravenous Thrombolysis After Reversal of Dabigatran With Idarucizumab in Acute Ischemic Stroke: A Case Report.

Background: As there is a growing concern about the cerebral embolism events secondary to non-valvular atrial fibrillation (NVAF), novel oral anticoagulant (NOAC) has been more and more widely used as an anticoagulation treatment for the prevention of stroke. However, in the face of life-threatening bleeding or emergency surgery/treatment, NOAC-related antagonists such as idarucizumab need to be urgently used to reverse the NOAC. Using recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis for acute ischemic stroke requires a time window of 4.5 h. This case reports rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab in patients with acute ischemic stroke. Case Presentation: We report the case of 62-year-old Chinese female with NVAF treated with dabigatran 110 mg twice daily, and missed a dose on the eve of the stroke. The patient presented with acute ischemic stroke causing the angle of mouth deviated to right side and left limb weakness in the early morning of the next day. However, the last dosing time of dabigatran was between 24 and 48 h, the patients were given rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab, while any potential relative contraindication had been excluded by means of laboratory test and CT scan in the hospitalization services. National Institute of Health stroke scale (NIHSS) score was reduced from 4 to 1, and the patient was discharged after 2 weeks. Conclusion: Our case report adds to the evidence that idarucizumab administration is safe and effective in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring rt-PA intravenous thrombolysis.

The Effect of Ryegrass Silage Feeding on Equine Fecal Microbiota and Blood Metabolite Profile.

Silage is fed to horses in China and other areas in the world, however, knowledge about the impact of feeding silage on horse health is still limited. In the current study, 12 horses were assigned into two groups and fed ryegrass silage and ryegrass hay, respectively, for 8 weeks. High-throughput sequencing was applied to analyze fecal microbiota, while liquid chromatography-tandem mass spectrometry (LC-MS/MS) based metabolomics technique was used for blood metabolite profile to investigate the influence of feeding ryegrass silage (group S) compared to feeding ryegrass hay (group H) on equine intestinal and systemic health. Horses in group S had significantly different fecal microbiota and blood metabolomes from horses in group H. The results showed that Verrucomicrobia was significantly less abundant which plays important role in maintaining the mucus layer of the hindgut. Rikenellaceae and Christensenellaceae were markedly more abundant in group S and Rikenellaceae may be associated with some gut diseases and obesity. The metabolomics analysis demonstrated that ryegrass silage feeding significantly affected lipid metabolism and insulin resistance in horses, which might be associated with metabolic dysfunction. Furthermore, Pearson's correlation analysis revealed some correlations between bacterial taxa and blood metabolites, which added more evidence to diet-fecal microbiota-health relationship. Overall, ryegrass silage feeding impacted systemic metabolic pathways in horses, especially lipid metabolism. This study provides evidence of effects of feeding ryegrass silage on horses, which may affect fat metabolism and potentially increase risk of insulin resistance. Further investigation will be promoted to provide insight into the relationship of a silage-based diet and equine health.

Effects of Pasture Grass, Silage, and Hay Diet on Equine Fecal Microbiota.

Diet is an important factor affecting intestinal microbiota in horses. Fecal microbiota is commonly used as a substitute for studying hindgut microbiota when investigating the relationship between intestinal microbial changes and host health. So far, no study has compared the difference between the fecal microbiota found in horses that are fed pasture grass, silage, and hay. The present study aims to characterize the fecal microbiota in horses that were exclusively on one of the three forage diets, and to analyze the potential impact of these forages, especially silage, on horse intestinal health. There were 36 horses randomly assigned to each of the three groups; each group was fed only one type of forage for 8 weeks. High throughput sequencing was applied to analyze the bacterial taxa in fecal samples collected from the horses at the end of the feeding trial. The Lachnospiraceae family was statistically more abundant in horses fed with hay, while it was the least abundant in horses fed with silage. The Streptococcaceae spp., considered a core microbial component in equine intestinal microbiota, were present in significantly lower quantities in feces from horses that were fed pasture grass as compared to those from horses fed hay or silage. The novel data may help promote the balancing of horse intestinal microbiota and the maintenance of intestinal health in horses.

Extracellular phosphorylation drives the formation of neuronal circuitry.

Until recently, the existence of extracellular kinase activity was questioned. Many proteins of the central nervous system are targeted, but it remains unknown whether, or how, extracellular phosphorylation influences brain development. Here we show that the tyrosine kinase vertebrate lonesome kinase (VLK), which is secreted by projecting retinal ganglion cells, phosphorylates the extracellular protein repulsive guidance molecule b (RGMb) in a dorsal-ventral descending gradient. Silencing of VLK or RGMb causes aberrant axonal branching and severe axon misguidance in the chick optic tectum. Mice harboring RGMb with a point mutation in the phosphorylation site also display aberrant axonal pathfinding. Mechanistic analyses show that VLK-mediated RGMb phosphorylation modulates Wnt3a activity by regulating LRP5 protein gradients. Thus, the secretion of VLK by projecting neurons provides crucial signals for the accurate formation of nervous system circuitry. The dramatic effect of VLK on RGMb and Wnt3a signaling implies that extracellular phosphorylation likely has broad and profound effects on brain development, function and disease.

Transplant long-surviving induced by CD40-CD40 ligand costimulation blockade is dependent on IFN-γ through its effect on CD4(+)CD25(+) regulatory T cells.

BACKGROUND: IFN-γ was documented to be commonly associated with acute rejection. In the present study, we investigated the role of IFN-γ in the transplant long-surviving induced by blocking CD40-CD40 ligand (CD40-CD40L) costimulation and its mechanisms. METHODS: IFN-γ expression in cardiac allografts and spleens from syngeneic and allogeneic recipients with or without anti-CD40L monoclonal antibody (MR-1) treatment was examined by real-time RT-PCR. The grafts survival time in Wild type (IFN-γ(+/+)) and IFN-γ deficient (IFN-γ(-/-)) recipients was investigated. Mixed lymphocyte reaction (MLR) of CD4(+) T cells and cytotoxic T lymphocyte (CTL) assay of CD8(+) T cells were also studied. FoxP3 expression in allografts and spleens from IFN-γ(+/+) or IFN-γ(-/-) recipients with MR-1 treatment was examined. Furthermore, FoxP3, IL-10 and CTLA-4 expressions and the suppressive capability of CD4(+)CD25(+) regulatory T cells were examined. RESULTS: Rejected allografts showed significantly higher IFN-γ expression than long-surviving allografts. Allograft survival was not prolonged in nonimmunosuppressed IFN-γ(-/-) mice. Administration of MR-1 induced long-term survival in 90.1% of IFN-γ(+/+) recipients (98±6.6 days) but failed to do so in IFN-γ(-/-) group (16.2±4.0 days). IFN-γ(-/-) recipients facilitated the proliferation and CTL generation of T cells. The allografts and spleens from IFN-γ(+/+) recipients contained higher FoxP3 expression than IFN-γ(-/-) recipients. Moreover, CD4(+)CD25(+) T cells from IFN-γ(+/+) recipients displayed a higher FoxP3 and IL-10 expression and suppressive capability. CONCLUSION: IFN-γ plays an important role in the long-surviving induced by blocking CD40-CD40L through inhibiting the function of activated T cells and increasing suppressive capability of CD4(+)CD25(+) regulatory T cells.

Cardiac allograft acceptance induced by blockade of CD40-CD40L costimulation is dependent on CD4+CD25+ regulatory T cells.

BACKGROUND: We have demonstrated previously that CD4(+)CD25(+) regulatory T cells (Treg) are important for spontaneous hepatic allograft tolerance. In this study, we examine the role of Treg in cardiac allograft acceptance induced by blockade of the CD40-CD40L pathway. METHODS: A heterotopic heart transplant model of major histocompatibility complex-mismatched mice was performed. Expression of forkhead/winged helix transcription factor (FoxP3) and/or the number of CD4(+)CD25(+) T cells in allografts and spleens were examined. The effect of Treg from the recipient or the donor on the induction and maintenance of long-term allograft survival was determined. Histologic analyses were also performed. The effects of Treg on CD4(+) and CD8(+) T cells were assessed. RESULTS: The levels of FoxP3 and/or CD4(+)CD25(+) T cells increased in long-surviving allografts and spleens. Depletion of Treg in the recipients but not the donors before transplantation caused rejection. Histologic analyses of allografts with Treg depletion showed extensive leukocyte infiltration and tissue destruction. However, delayed depletion of Treg in long-surviving recipients did not shorten their survival. Treg depletion increased the function of CD4(+) and CD8(+) T cells. CONCLUSION: Treg in the recipient but not in the donor is essential for long-term survival induced by CD40-CD40L blockade by inhibiting the function of CD4(+) and CD8(+) T cells; however, Treg are not important for maintenance. Both allograft and spleen are critical for induction of successful long-term survival.

CD40-CD40L costimulation blockade induced the tolerogenic dendritic cells in mouse cardiac transplant.

We aimed to investigate whether tolerogenic dendritic cells (DCs) were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation. Mouse heterotopic heart transplantation was performed. DCs were sorted from rejected and tolerant recipients using magnetic-activated cell sorting. Their expression of CD40, CD80, and CD86 was examined using fluorescence-activated cell sorting. DCs were stimulated with lipopolysaccharide in vitro, and interleukin 10 (IL-10) and IL-12 levels in the supernatants were evaluated using enzyme-linked immunosorbent assay. By using mixed leukocyte reaction, we investigated the stimulatory capacities and tolerogenic capability of DCs. DCs from tolerant recipients expressed lower level of costimulatory molecules, including CD40, CD80, and CD86 and released higher levels of IL-10 and lower levels of IL-12. In addition, DCs from tolerant recipients were weak stimulators of the mixed leukocyte reaction and inhibited the proliferation of splenocytes. IL-10(high)IL-12(low) DCs with immature phenotype were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation, and they obtained the tolerogenic function.

Expansion of CD25+CD4+ regulatory T cells by natural mature dendritic cells.

Because of the anergy of CD25+CD4+ regulatory T cells, it is unclear how the number of these regulatory T cells is sustained and expanded in normal physiologic circumstances. In the present study, we examined the effect of natural allogeneic mature dendritic cells (DCs) on the proliferation and function of CD25+CD4+ T cells. Our data showed that natural allogeneic mature DCs stimulated CD25+CD4+ T-cell growth vigorously, whereas immature DCs had little effect on the proliferation of CD25+CD4+ T cells. After expansion by mature DCs, CD25+CD4+ T cells maintained their expression of Foxp3 and suppressed the proliferation of CD25- CD4+ T cells similar to freshly isolated CD25+CD4+ T cells. Our results introduce a potentially critical role played by natural allogeneic mature DCs, which exist in normal physiologic circumstances, in controlling CD25+CD4+ regulatory T-cell expansion and function.