Quality of Sediment Organic Matter Determines the Intertidal N2O Response to Global Warming

Estuaries and coasts are areas of intense biogeochemical cycling and are sensitive to global climate change. However, the effect of temperature increase on the emissions of the powerful greenhouse gas nitrous oxide (N2O) in different estuarine and coastal areas is still uncertain. In this study, we used laboratory incubation experiments to investigate increasing temperatures (12, 25, and 35 degrees C) and tidal effects on N2O fluxes in intertidal sediments from the East China coast (ECC). Overall, the ECC acts as a net source of atmospheric N2O and exhibited considerable spatial variability over three orders of magnitude (from -0.17 to 8.4 mu mol m(-2) h(-1)). The warming promoted N2O emissions in most intertidal areas, while reducing N2O emissions at some sampling sites. In addition, the overall effect of flooding on N2O emissions changed from a positive to a negative effect with increasing temperature. By combining the sediment properties of all the sampling sites, we found that large differences in N2O emissions at the same amended floodwater nitrogen concentration were due to the quality and quantity of sediment organic matter. Sediment derived mainly from marine sources emitted more N2O than sediment derived from terrestrial sources. This suggests that the mangroves, salt marshes, and intertidal zones of estuaries have a mitigating effect on N2O emissions due to their elevated terrestrial organic matter inputs. This research improves our understanding of the impact of future global climatic changes on intertidal N2O fluxes, which can inform future studies and models and can be used to constrain intertidal N2O emissions

Polyphyllin VI screened from Chonglou by cell membrane immobilized chromatography relieves inflammatory pain by inhibiting inflammation and normalizing the expression of P2X₃ purinoceptor

Objective: Inflammatory pain is one of the most common diseases in daily life and clinic. In this work, we analysed bioactive components of the traditional Chinese medicine Chonglou and studied mechanisms of their analgesic effects. Material and methods: Molecular docking technology and U373 cells overexpressing P2X3 receptors combined with the cell membrane immobilized chromatography were used to screen possible CL bioactive molecules interacting with the P2X3 receptor. Moreover, we investigated the analgesic and anti-inflammatory effects of Polyphyllin VI (PPIV), in mice with chronic neuroinflammatory pain induced by CFA (complete Freund’s adjuvant). Results: The results of cell membrane immobilized chromatography and molecular docking showed that PPVI was one of the effective compounds of Chonglou. In mice with CFA-induced chronic neuroinflammatory pain, PPVI decreased the thermal paw withdrawal latency and mechanical paw withdrawal threshold and diminished foot edema. Additionally, in mice with CFA-induced chronic neuroinflammatory pain, PPIV reduced the expression of the pro-inflammatory factors IL-1, IL-6, TNF-α, and downregulated the expression of P2X3 receptors in the dorsal root ganglion and spinal cord. Conclusion: Our work identifies PPVI as a potential analgesic component in the Chonglou extract. We demonstrated that PPVI reduces pain by inhibiting inflammation and normalizing P2X3 receptor expression in the dorsal root ganglion and spinal cord.</p

ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4⁺ Th1 responses

Parasite-specific CD4+ Th1 cell responses are the predominant immune effector for controlling malaria infection; however, the underlying regulatory mechanisms remain largely unknown. This study demonstrated that ATG5 deficiency in myeloid cells can significantly inhibit the growth of rodent blood-stage malarial parasites by selectively enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency suppressed FAS-mediated apoptosis of LY6G− ITGAM/CD11b+ ADGRE1/F4/80− cells and subsequently increased CCL2/MCP-1 production in parasite-infected mice. LY6G− ITGAM+ ADGRE1− cell-derived CCL2 selectively interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2-STAT4 pathway. The administration of recombinant CCL2 significantly promoted parasite-specific CD4+ Th1 responses and suppressed malaria infection. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cells apoptosis and sequentially affecting CCL2 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of immune interventions and effective anti-malarial vaccines. Abbreviations: ATG5: autophagy related 5; CBA: cytometric bead array; CCL2/MCP-1: C-C motif chemokine ligand 2; IgG: immunoglobulin G; IL6: interleukin 6; IL10: interleukin 10; IL12: interleukin 12; MFI: mean fluorescence intensity; JAK2: Janus kinase 2; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; pRBCs: parasitized red blood cells; RUBCN: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; STAT4: signal transducer and activator of transcription 4; Th1: T helper 1 cell; Tfh: follicular helper cell; ULK1: unc-51 like kinase 1.</p