Differential responses of soil phosphorus fractions to varied nitrogen compound additions in a meadow steppe.

Nitrogen (N) addition can greatly influence soil inorganic phosphorus (Pi) and organic phosphorus (Po) transformations. However, whether and how the N compound forms may differentially affect the soil P fractions remain unclear. Here, we investigated the responses of soil Pi (labile Pi, moderately-occluded Pi, and recalcitrant Pi) and Po fractions (labile Po and stable Po) to varying addition rates of three N compounds ((NH4)2SO4, NH4NO3, and urea) in a meadow steppe in northern China. Our studies revealed that with increasing N addition rate, soil labile and moderately-occluded Pi increased, accompanied by decreases in soil recalcitrant Pi. This shift was attributed to N-induced soil acidification, which accelerated the conversion of recalcitrant Pi into labile and moderately-occluded Pi. Soil labile Po decreased with increasing rate of N addition, whilst soil stable Po was not affected. Regardless of the compound forms, N addition increased soil Olsen-P, suggesting a potential alleviation of P limitation in this grassland ecosystem. The effect of N addition on soil labile Pi was significantly greater with addition of urea than with addition of either (NH4)2SO4 or NH4NO3, indicating that urea was more efficient in enhancing soil P availability. Addition of (NH4)2SO4 imposed a more pronounced positive effect on soil moderately-occluded Pi than the addition of either NH4NO3 or urea, mainly due to the greater mobilization of recalcitrant Pi as a result of higher soil acidification strength of (NH4)2SO4. These findings underscore the importance of considering the distinct effects of different N compounds when studying grassland soil P dynamics and availability in response to N addition.

Genetically Predicted Vascular Proteins and Risk of Intracranial Aneurysms: A Mendelian Randomization Study.

The relationship between vascular proteins (VPs) and intracranial aneurysms (IAs) has not been fully elucidated. We used Mendelian randomization (MR) analysis to explore the effect of VPs on IAs. Dataset of aneurysmal subarachnoid hemorrhage (aSAH) [5140 cases and 71,934 controls] and unruptured intracranial aneurysm (uIA) [2070 cases and 71,934 controls] were obtained from individuals of European ancestry. Univariate MR was used to explore the associations between 90 VPs and IAs. Then, we performed multivariate MR (MVMR) to further investigate the identified VP-to-IA estimates. Two-sample MR showed that TNFSF14 was inversely associated with aSAH (odds ratio [OR] = 0.831, 95% CI: 0.713-0.969, p = 0.018). IL-16 (OR = 1.218, 95% CI: 1.032-1.438, p = 0.020) and AgRP (OR = 1.394, 95% CI: 1.048-1.855, p = 0.023) were positively associated with aSAH. HBEGF (OR = 0.642, 95% CI: 0.461-0.894, p = 0.009), MCP-1 (OR = 1.537, 95% CI: 1.007-2.344, p = 0.046), and CX3CL1 (OR = 0.762, 95% CI: 0.581-0.999, 0.049 < p < 0.050) were associated with uIA risk. The MVMR showed that the TNFSF14-to-aSAH estimate remained statistically significant after adjustment for past tobacco smoking, alcohol consumption, systolic blood pressure and body mass index. Our study indicated that low serum TNFSF14 levels might be a potential risk factor for IA rupture. Five VPs (HBEGF, MCP-1, IL-6, CX3CL1, and AgRP) are associated with the risk of IAs (both uIA and aSAH).

Applied phosphorus is maintained in labile and moderately occluded fractions in a typical meadow steppe with the addition of multiple nutrients.

Phosphorus (P) is a limiting nutrient second only to nitrogen (N) in the drylands of the world. Most previous studies have focused on N transformation processes in grassland ecosystems, particularly under artificial fertilization with N and atmospheric N deposition. However, P cycling processes under natural conditions and when P is applied as an inorganic P fertilizer have been understudied. Therefore, it is essential to examine the fate of applied P in grassland ecosystems that have experienced long-term grazing and, under certain circumstances, continuous hay harvest. We conducted a 3-year field experiment with the addition of multiple nutrient elements in a typical meadow steppe to investigate the fate of the applied P in various fractions of P pools in the top soil. We found that the addition of multiple nutrients significantly increased P concentrations in the labile inorganic P (Lab-Pi) and moderately occluded inorganic P (Mod-Pi) fractions but not in the recalcitrant inorganic P (Rec-Pi) fraction. An increase in the concentration of total inorganic P was found only when P and N were applied together. However, the addition of other nutrients did not change P concentrations in any fraction of the mineral soil. The addition of P and N significantly increased the total amount of P taken up by the aboveground plants but had no effect on the levels of organic and microbial P in the soil. Together, our results indicate that the P applied in this grassland ecosystem is taken up by plants, leaving most of the unutilized P as Lab-Pi and Mod-Pi rather than being immobilized in Rec-Pi or by microbial biomass. This implies that the grassland ecosystem that we studied has a relatively low P adsorption capacity, and the application of inorganic P to replenish soil P deficiency in degraded grasslands due to long-term grazing of livestock or continuous harvest of forage in the region could be a practical management strategy to maintain soil P fertility.

NLRP3 inflammasome inhibitor MCC950 reduces cerebral ischemia/reperfusion induced neuronal ferroptosis.

The role of nucleotide-binding oligomerization domainlike receptor pyrin domain containing 3 (NLRP3) inflammasome in cerebral ischemia-reperfusion (I/R) induced neuroinflammation and neuronal pyroptosis has been widely recognized. Latest studies revealed that NLRP3 inflammasome engage in not only pyroptosis but also other types of cell death. Ferroptosis has been proved to be closely associated with cerebral I/R injury. In this study, our objectives were to verify the inhibitory effect of the NLRP3-specific inhibitor MCC950 on cerebral I/R-mediated neuronal pyroptosis, and to explore the regulation and possible mechanism of MCC950 on cerebral I/R-mediated neuronal ferroptosis. Our data showed that the NLRP3-specific inhibitor, MCC950, effectively reversed the I/R-mediated NLRP3 inflammasome activation and neuronal pyroptosis. Furthermore, we found that I/R increased iron concentrations and levels of malondialdehyde (MDA), downregulated glutathione peroxidase 4 (GPX4) expression, and upregulated long chain fatty acid-CoA ligase 4 (FACL4) and prostaglandin endoperoxide synthase 2 (PTGS2) expression. Interestingly, these changes were also reversed by the MCC950. Finally, in vitro, we found that MCC950 significantly reduced ROS levels in OGD/R treated HT22 cells. In conclusion, pharmaceutical inhibition of NLRP3 by MCC950 attenuates I/R-induced neuronal ferroptosis, possibly by reducing ROS accumulation.

Inhibition of PRMT5 attenuates cerebral ischemia/reperfusion-Induced inflammation and pyroptosis through suppression of NF-κB/NLRP3 axis.

Protein methylation is a prevalent post-translational modification after cerebral ischemia. Protein arginine methyltransferase 5 (PRMT5) is a type of methyltransferase enzyme that can catalyse the formation of methylated residues on histones and non-histone proteins. Accumulating evidence suggested that PRMT5 might play a carcinogenic role in various cancers. However, the role of PRMT5 in cerebral ischaemia/reperfusion (I/R) injury remains unclear. In this project, middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) model in human neuroblastoma SH-SY5Y cells were utilized to mimic disease state of cerebral I/R. We found that expression of inflammatory-related factors [Interleukin (IL)-1ß and IL-6)] and pyroptotic-related factor [N-term cleaved Gasdermin-D (GSDMD-N)] were up-regulated in both MCAO/R mice and OGD/R SH-SY5Y cells. In addition, both in vivo and in vitro, PRMT5 was aberrantly upregulated during cerebral I/R. However, these alterations induced by I/R were blocked by PRMT5 inhibitor LLY-283, and enhanced by overexpression of PRMT5. Furthermore, rescue experiment proved that PRMT5 plays a pro-inflammatory and pro-pyroptotic role by activating nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domainlike receptor pyrin domain containing 3 (NLRP3) axis. Finally, we observed that treatment of LLY-283 alleviated neurological deficits and reduced infarct volume in the MCAO/R mice. Taken together, PRMT5 may be a potential therapeutic target for cerebral I/R injury.