Acrolein (ACR) is a ubiquitous environmental pollutant and byproduct of lipid peroxidation that has been implicated in male infertility. However, the molecular mechanisms underlying ACR-induced toxicity in Sertoli cells remain unclear. Given its role in inducing oxidative stress, we examined whether ferroptosis, an iron-dependent form of regulated cell death, could mediate ACR toxicity in Sertoli cells. We also tested if hydrogen sulfide (H2S), which has antioxidant and ACR detoxifying properties, could protect Sertoli cells from ACR-induced ferroptosis. ACR exposure decreased Sertoli cell viability, increased protein carbonylation and p38 MAPK phosphorylation, indicating oxidative injury. ACR also depleted glutathione (GSH), downregulated the cystine importer SLC7A11, increased intracellular ferrous iron (Fe2+) and lipid peroxidation, suggesting activation of ferroptosis. Consistently, the ferroptosis inhibitor deferoxamine (DFO) markedly attenuates ACR-induced cell death. Further studies revealed that ACR-induced ferroptotic changes were prevented by exogenous H2S and exaggerated by inhibition of endogenous H2S production. Furthermore, H2S also suppressed GPX4 inhibitor RSL3-induced intracellular ACR accumulation and ferroptosis. In summary, our study demonstrates that ACR induces ferroptotic cell death in Sertoli cells, which can be prevented by H2S through multiple mechanisms. Targeting the H2S pathway may represent a therapeutic strategy to mitigate ACR-induced Sertoli cell injury and preserve male fertility.

Hydrogen sulfide (H2S) is a poisonous pollutant that endangers the environment, and H2S is also produced during food spoilage. Herein, we constructed a dicyanoisophorone-based near-infrared (NIR) fluorescent probe (DCID) to detect H2S. DCID exhibited significant turn-on fluorescence at 700 nm with a low limit of detection (LOD = 74 nM), large Stokes shift (220 nm), prominent selectivity, and response time (100 s) toward H2S. Importantly, the DCID probe had powerful applications in the detection of H2S in environmental samples and food spoilage. In addition, based on DCID-loaded test strips and combined a smartphone sensing platform, which provided a portable and convenient approach for the detection of H2S.

Necroptosis is a programmed cell death form executed by receptor-interacting protein kinase (RIPK) 1, RIPK3 and mixed lineage kinase domain-like protein (MLKL), which assemble into an oligomer called necrosome. Accumulating evidence reveals that necroptosis participates in many types of pathological processes. Hence, clarifying the mechanism of necroptosis in pathological processes is particularly important for the prevention and treatment of various diseases. For over 300 years, hydrogen sulfide (H2S) has been widely known in the scientific community as a toxic and foul-smelling gas. However, after discovering the important physiological and pathological functions of H2S, human understanding of this small molecule changed, believing that H2S is the third gas signaling molecule after carbon monoxide (CO) and nitric oxide (NO). H2S plays an important role in various diseases, but the related mechanisms are not yet fully understood. In recent years, more and more studies have shown that H2S regulation of necroptosis is involved in various pathological processes. Herein, we focus on the recent progress on the role of H2S regulation of necroptosis in different pathological processes and profoundly analyze the related mechanisms.

OBJECTIVE: Hydrogen sulfide (H2S) secreted by perivascular adipose tissue (PVAT) is a critical vasodilator, which might be involved during the pathogenesis of hypertension. The present study aimed to investigate the exact role of H2S on the regulation of PVAT anti-contraction by long-term exercise in obesity hypertension.
METHODS: After the establishment of obesity hypertension (24 weeks) through a high-fat diet, male Sprague-Dawley rats were randomly assigned to control group (HC), exercise group (HE), cystathionine γ-lyase (CSE) blocking group (HCB), and exercise combined with CSE blocking group (HEB). Exercise and CSE inhibitor regimens were performed throughout 13 weeks.
RESULTS: After 13 weeks of intervention, blood pressure was significantly decreased by long-term exercise (HC vs. HE, P < 0.05) but not by exercise combined with the CSE inhibitor regimen. Meanwhile, the CSE inhibitor significantly blocked the production of H2S in PVAT even after exercise (HE vs. HEB, P < 0.05). Furthermore, long-term exercise altered the expressions of voltage-dependent K+ (Kv) channel subunits 7 (KCNQs), which were diminished by CSE inhibition in mesenteric arteries. As for vascular tension assessment, after incubation with or without KCNQ opener (retigabine), the anti-contractile effect of PVAT (with or without transferred bath solution of PVAT) was significantly enhanced by long-term exercise and eliminated by the CSE inhibitor regimen (P < 0.05); KCNQ inhibitor (XE991) blunted this effect except for HE.
CONCLUSIONS: These results collectively suggest that endogenous H2S is a strong regulator of the anti-contractile effect of PVAT in obesity hypertension by long-term exercise, and KCNQ in the resistance artery might be involved during this process but not the only target channel mediated by H2S.

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

Landfill mining (LFM) has gained widespread recognition due to its benefits in terms of resource utilization of landfill waste and reuse of landfill sites. However, it is important to thoroughly assess the associated environmental risks. This study simulated the pressure release induced from LFM in small-scale batch anaerobic reactors subject to different initial pressures (0.2-0.6 MPa). The potential risk of hydrogen sulfide (H2S) pollution resulting from pressure release caused by LFM was investigated. The results demonstrated that the concentration of H2S significantly increased following the simulated pressure treatments. At the low (25 °C) and high (50 °C) temperatures tested, the peak H2S concentration reached 19366 and 24794 mg·m-3, respectively. Both of these concentrations were observed under highest initial pressure condition (0.6 MPa). However, the duration of H2S release was remarkably longer (>90 days) at the low temperature tested. Microbial diversity analysis results revealed that, at tested low temperature, the sulfate-reducing bacteria (SRB) communities of various pressure-bearing environments became phylogenetically similar following the pressure releases. In contrast, at the high temperature tested, specific SRB genera (Desulfitibacter and Candidatus Desulforudis) showed further enrichment. Moreover, the intensified sulfate reduction activity following pressure release was attributed to the enrichment of specific SRBs, including Desulfovibrio (ASV585 and ASV1417), Desulfofarcimen (ASV343), Candidatus Desulforudis (ASV24), and Desulfohalotomaculum (ASV506 and ASV2530). These results indicate that the pressure release associated with LFM significantly increases the amount of H2S released from landfills, and the SRB communities have different response mechanisms to pressure release at different temperature conditions. This study highlights the importance of considering the potential secondary environmental risks associated with LFM.

A BiVO4/Fe2O3 heterojunction for non-enzymatic photoelectrochemical (PEC) determination of hydrogen sulfide (H2S) is reported. The BiVO4/Fe2O3 heterojunction promoted the separation of photo-generated carriers, reduced electron-hole recombination, and thus improved electron collection and photocurrent. The proposed BiVO4/Fe2O3/FTO sensor exhibited a linear range of 1-500 μM and a detection limit of 0.51 nM H2S. In addition, high selectivity, good reproducibility, and stability were obtained for H2S sensing. The detection of H2S in water and serum samples demonstrated its feasibility. This work provides a new strategy to detect and understand the bio-function of H2S in the biological environment.

Hydrogen sulfide (H2S) is a crucial endogenous gasotransmitter that plays a role in various physiological and pathological processes. Therefore, accurate and rapid monitoring of H2S in organisms is highly significant for understanding the underlying pathological mechanisms and facilitating early diagnosis of related diseases. In this study, we developed a novel fluorescent probe, B-CHO-NO2, based on a bodipy fluorophore, which exhibits excellent sensitivity and selectivity towards H2S. The design of the probe exploits the nucleophilicity of H2S by introducing a formyl group as the ortho-participating moiety, significantly enhancing the reaction rate with H2S. In cellular and zebrafish models, the probe B-CHO-NO2 successfully achieved fluorescence imaging of endogenous and exogenous H2S. The development of probe B-CHO-NO2 provides a powerful tool for biological studies of H2S and diagnosis of related diseases.

It has been well established that Hydrogen sulfide (H2S) is involved in various pathophysiological processes. Therefore, accurate monitoring H2S levels in vitro or vivo is of great significance in biological systems. Herein, we firstly developed a thiomaleimide-based compound MAL-1 bearing aggregation-induced emission characteristic for selective response toward H2S due to its nucleophilicity. The proposed sensor presented prominent sensitivity and selectivity with low detection limit of 75 nM and pseudo-first-order reaction rate constant of 9.65 × 10-2 s-1, as well as low cytotoxicity which works well in recognizing H2S in real samples and visualizing H2S in living cells. Thus, it could be concluded that the novel thiomaleimide-based probe would be a promising tool for assessing intracellular H2S levels.