Hydrogen sulfide (H₂S) has been recently recognized as an important gasotransmitter with cardioprotections, and iron is vital for various cellular activities. This study explored the regulatory role of H₂S on iron metabolism and mitochondrial functions in cultured rat cardiac cells. Rotenone, a mitochondrial complex I inhibitor, was used for establishing an in vitro model of ischemic cell damage. It was first found that rotenone induced oxidative stress and lipid peroxidation and decreased mitochondrial membrane potential and ATP generation, eventually causing cell death. The supplement of H₂S at a physiologically relevant concentration protected from rotenone-induced ferroptotic cell death by reducing oxidative stress and mitochondrial damage, maintaining GPx4 expression and intracellular iron level. Deferiprone, an iron chelator, would also protect from rotenone-induced ferroptosis. Further studies demonstrated that H₂S inhibited ABCB8-mediated iron efflux from mitochondria to cytosol and promoted NFS1-mediated Fe-S cluster biogenesis. It is also found that rotenone stimulated iron-dependent H₂S generation. These results indicate that H₂S would protect cardiac cells from ischemic damage through preserving mitochondrial functions and intracellular Fe-S cluster homeostasis.

A two-year field experiment was performed to investigate effects on greenhouse gas emissions from rice straw return to different return depths and soil types. The experiment comprised of six treatments: without straw return (silty clay loam, SC; sandy loam, SL); straw return to topsoil (SCT, SLT); and straw return to subsoil (SCS, SLS). SCT and SLT released 2402.18 and 2494.01 kg ha⁻¹ more CO₂ than SC and SL in total, respectively. Straw return to topsoil and subsoil in both soil textures significantly increased CH₄ emissions. Compared to the total cumulative CH₄ fluxes in SC and SL, those of SCT and SLT increased by 239.62 and 131.34 kg ha⁻¹, and those of SCS and SLS increased by 125.07 and 89.93 kg ha⁻¹, respectively. SCT and SCS emitted 389.06 and 168.94 g ha⁻¹ less N₂O than SC in total, respectively. SL released 146.28 and 72.06 g ha⁻¹ more N₂O than SLT and SLS in total, respectively. The variations in the ratio of the total cumulative fluxes of CO₂ and CH₄, indicate that rice straw return to silty clay loam and subsoil tend to release more organic carbon in the form of CH₄ compared to sandy loam and topsoil, respectively.

Nowadays, emerging evidence have suggested that the ferroptosis of macrophages could contribute to the progression of atherosclerosis (AS). Meanwhile, Spermine (Sp) could serve as an endogenous small molecule exhibiting a wide range of cardiovascular protective effects. Zeolitic imidazolate framework-90 (ZIF90) nanoparticles were synthesized and utilized to create a novel delivery nanosystem encapsulated with Sp (CD16/32-ZIF90@Sp). The efficacy of CD16/32-ZIF90@Sp in protecting against AS and ferroptosis was evaluated in ApoE−/− mice and macrophages, with a focus on assessing potential adverse effects in vivo. CD16/32-ZIF90@Sp exhibited reliable and stable delivery of Sp within acidic environments and ATP sensitivity. CD16/32-ZIF90@Sp effectively reduced the cytotoxicity of Sp. As is evidenced by in vitro and vivo experiments, CD16/32-ZIF90@Sp showed precise targeting of macrophages within atherosclerotic plaques and ox-LDL-activated macrophages. Furthermore, treatment with CD16/32-ZIF90@Sp effectively attenuated the progression of AS and the ferroptosis of macrophage within plaque in ApoE−/− mice without causing significant side effects. Mechanistically, we found that CD16/32-ZIF90@Sp inhibited ferroptosis via improving mitochondrial function and upregulating the expression level of GPX4/xCT. Our study demonstrated that CD16/32-modified ZIF90 nanoparticles could effectively target macrophages within atherosclerotic plaques, leading to the inhibition of atherosclerotic plaque progression in ApoE−/− mice. These effects were attributed to the enhancement of mitochondrial function and the inhibition of macrophage ferroptosis, with limited side effects.

Maternal diabetes during pregnancy increases the risk of metabolic and cardiac disorders in offspring. Nevertheless, the mechanism by which intrauterine hyperglycemia affects neonatal cardiac remodeling remains uncertain. This study aims to characterize the prenatal environment in the context of gestational diabetes mellitus and to identify the corresponding fetal changes. Using an intrauterine hyperglycemia rodent model, we observe cardiac remodeling and inflammatory responses in offspring hearts. Moreover, the O -GlcNAcylation levels are increased in neonatal hearts exposed to gestational diabetes. Further mechanistic investigations, supported by RNA sequencing and mitochondrial functional analyses, reveal that gestational diabetes triggers O -GlcNAcylation-dependent activation of CaMKIIδ during the embryonic stage. This activation leads to the release of mitochondrial DNA (mtDNA) from the mitochondrial matrix into the cytosol, which subsequently activates STING signaling and triggers an inflammatory response in neonatal cardiomyocytes. Pharmacological or genetic inhibition of O -GlcNAcylation attenuates mtDNA-induced myocardial inflammation and improves cardiac function in neonatal offspring subjected to intrauterine hyperglycemia. Together, these findings identify a previously unrecognized CaMKIIδ/mtDNA/STING axis in which CaMKIIδ O -GlcNAcylation leads to mtDNA-dependent activation of cardiac remodeling, suggesting that plasma mtDNA levels could serve as a predictive biomarker in neonatal cardiac inflammatory injury.