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As the closest transiting hot Jupiter to Earth, HD 189733b has been the benchmark planet for atmospheric characterization 1 – 3 . It has also been the anchor point for much of our theoretical understanding of exoplanet atmospheres from composition 4 , chemistry 5 , 6 , aerosols 7 to atmospheric dynamics 8 , escape 9 and modelling techniques 10 , 11 . Previous studies of HD 189733b have detected carbon and oxygen-bearing molecules H 2 O and CO (refs.  12 , 13 ) in the atmosphere. The presence of CO 2 and CH 4 has been claimed 14 , 15 but later disputed 12 , 16 , 17 . The inferred metallicity based on these measurements, a key parameter in tracing planet formation locations 18 , varies from depletion 19 , 20 to enhancement 21 , 22 , hindered by limited wavelength coverage and precision of the observations. Here we report detections of H 2 O (13.4 σ ), CO 2 (11.2 σ ), CO (5 σ ) and H 2 S (4.5 σ ) in the transmission spectrum (2.4–5.0 μm) of HD 189733b. With an equilibrium temperature of about 1,200 K, H 2 O, CO and H 2 S are the main reservoirs for oxygen, carbon and sulfur. Based on the measured abundances of these three main volatile elements, we infer an atmospheric metallicity of three to five times stellar. The upper limit on the methane abundance at 5 σ is 0.1 ppm, which indicates a low carbon-to-oxygen ratio (<0.2), suggesting formation through the accretion of water-rich icy planetesimals. The low oxygen-to-sulfur and carbon-to-sulfur ratios also support the planetesimal accretion formation pathway 23 . The exoplanet HD 189733b has a metal-enriched atmosphere with the possible presence of H 2 O (13.4 σ ), CO 2 (11.2 σ ), CO (5 σ ) and H 2 S (4.5 σ ).

Central nervous system (CNS)-related conditions are currently the leading cause of disability worldwide, posing a significant burden to health systems, individuals and their families. Although the molecular mechanisms implicated in these disorders may be varied, neurological conditions have been increasingly associated with inflammation and/or impaired oxidative response leading to further neural cell damages. Therefore, therapeutic approaches targeting these defective molecular mechanisms have been vastly explored. Hydrogen sulphide (H 2 S) has emerged as a modulator of both inflammation and oxidative stress with a neuroprotective role, therefore, has gained interest in the treatment of neurological disorders. H 2 S, produced by endogenous sources, is maintained at low levels in the CNS. However, defects in the biosynthetic and catabolic routes for H 2 S metabolism have been identified in CNS-related disorders. Approaches to restore H 2 S availability using H 2 S-donating compounds have been recently explored in many models of neurological conditions. Nonetheless, we still need to elucidate the potential for these compounds not only to ameliorate defective biological routes, but also to better comprehend the implications on H 2 S delivery, dosage regimes and feasibility to successfully target CNS tissues. Here, we highlight the molecular mechanisms of H 2 S-dependent restoration of neurological functions in different models of CNS disease whilst summarising current administration approaches for these H 2 S-based compounds. We also address existing barriers in H 2 S donor delivery by showcasing current advances in mediating these constrains through novel biomaterial-based carriers for H 2 S donors.

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.

• Hydrogen sulphide (H₂S) has been proposed as the third gasotransmitter. In animal cells, H₂S has been implicated in several physiological processes. H₂S is endogenously synthesized in both animals and plants by enzymes with l‐Cys desulphydrase activity in the conversion of l‐Cys to H₂S, pyruvate and ammonia. • The participation of H₂S in both stomatal movement regulation and abscisic acid (ABA)‐dependent induction of stomatal closure was studied in epidermal strips of three plant species (Vicia faba, Arabidopsis thaliana and Impatiens walleriana). The effect of H₂S on stomatal movement was contrasted with leaf relative water content (RWC) measurements of whole plants subjected to water stress. • In this work we report that exogenous H₂S induces stomatal closure and this effect is impaired by the ATP‐binding cassette (ABC) transporter inhibitor glibenclamide; scavenging H₂S or inhibition of the enzyme responsible for endogenous H₂S synthesis partially blocks ABA‐dependent stomatal closure; and H₂S treatment increases RWC and protects plants against drought stress. • Our results indicate that H₂S induces stomatal closure and participates in ABA‐dependent signalling, possibly through the regulation of ABC transporters in guard cells.

Short-chain fatty acids (SCFAs) are produced by various human gut microbes. SCFAs act as an energy source to the colonic epithelium and are also sensed by host signaling pathways that modulate appetite and inflammation. Deficiency of gut SCFAs is associated with type 2 diabetes. Zhao et al. found that adopting a high-fiber diet promoted the growth of SCFA-producing organisms in diabetic humans. The high-fiber diet induced changes in the entire gut microbe community and correlated with elevated levels of glucagon-like peptide-1, a decline in acetylated hemoglobin levels, and improved blood-glucose regulation. Science , this issue p. 1151 Increasing dietary fiber intake increases the abundance of short-chain fatty acid–producing gut microbes and relieves diabetes. The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

Key Points Hydrogen sulphide (H 2 S), together with nitric oxide and carbon monoxide, belongs to a family of labile biological mediators called gasotransmitters. H 2 S has long been known as a toxic gas emanating from sewers and as a by-product of industrial processes; however, the biological processes of sulphide and its metabolism and fate in biological systems is now beginning to be understood. H 2 S is synthesized endogenously in numerous mammalian tissues by two enzymes responsible for metabolizing L -cysteine — cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS). CBS is the predominant H 2 S-generating enzyme in the brain and nervous system. CSE is mainly expressed in the liver and in the vascular and non-vascular smooth muscle. Other sources of H 2 S include enterobacterial flora and inorganic sources. H 2 S exerts numerous biological effects on various biological targets, leading to responses that range from cytotoxic effects (due to free radical and oxidant generation) to cytoprotective (antinecrotic or anti-apoptotic) actions. In particular, H 2 S has been specifically shown to exert a pharmacological effect on potassium-opened ATP (K ATP ) channels. These opposing effects have been demonstrated in various animal models. Inhibition of sulphide in animal models of haemorrhagic shock has been demonstrated to accelerate the recovery of mean arterial pressure. H 2 S can also induce a suspended-animated-like state in mice — whether this can be achieved in larger animals remains to be seen. Protection from lethal hypoxic insult, myocardial injury and inflammation has also been shown. The options that could be explored to utilize this knowledge for therapeutic purposes are discussed. Two main pathways are considered viable: the development of inhibitors of CBS or CSE, and the development of H 2 S or H 2 S-releasing compounds. In this rapidly emerging field, there are still many unknowns — including the relationship of H 2 S with the other two gasotransmitters — however, further studies are likely to yield a number of therapeutic possibilities, and early stage drug candidates are already in development. Hydrogen sulphide (H 2 S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. This article overviews the physiology and biochemistry of H 2 S, summarizes the effects of H 2 S inhibitors or H 2 S donors in animal models of disease and discusses the likely options and paths for the therapeutic exploitation of H 2 S. Hydrogen sulphide (H 2 S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. The production of H 2 S from L -cysteine is catalysed primarily by two enzymes, cystathionine γ-lyase and cystathionine β-synthase. Evidence is accumulating to demonstrate that inhibitors of H 2 S production or therapeutic H 2 S donor compounds exert significant effects in various animal models of inflammation, reperfusion injury and circulatory shock. H 2 S can also induce a reversible state of hypothermia and suspended-animation-like state in rodents. This article overviews the physiology and biochemistry of H 2 S, summarizes the effects of H 2 S inhibitors or H 2 S donors in animal models of disease and outlines the potential options for the therapeutic exploitation of H 2 S.

Purpose Hydrogen sulphide (H 2 S) is an important signalling molecule involved in the regulation of several physiological and pathophysiological processes. The objective of this study was to investigate the feasibility of transdermal delivery of ADT-OH, a H 2 S donor, by investigating the transdermal flux of aqueous gels loaded with penetration enhancers or liposomes. Furthermore, we explored the ability of permeated ADT-OH to promote angiogenesis and mitochondrial bioenergetics in HUVEC cells. Methods Aqueous hypromellose gels (5% w/v) were prepared with up to 10% v/v propylene glycol (PG) or deformable liposomes with 0.025% w/w ADT-OH. ADT-OH permeation from formulations across excised murine skin into PBS was quantified over 24 h using HPLC-UV detection. Media was collected and applied to HUVEC cells to evidence ADT-OH functionality following permeation. Tube formation assays were performed as indicative of angiogenesis and mitochondrial oxygen consumption was evaluated using a Seahorse XF24. Results Increasing the loading of PG caused an increase in ADT-OH permeation rate across skin and a decrease in dermal drug retention whereas liposomal gels produced a slow-release profile. Treatment of HUVEC’s using conditioned media collected from the ADT-OH loaded permeation studies enhanced tube formation and the basal oxygen consumption rates after 30 min of treatment. Conclusions These findings demonstrate that transdermal delivery of ADT-OH may provide a promising approach in the treatment of impaired vascular function. Gels prepared with 10% v/v PG have the potential for use in conditions requiring rapid H 2 S release whereas liposomal loaded gels for treatment requiring sustained H 2 S release.

Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs.

The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H2S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro \"hyperglycemia\") induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H2S. Replacement of H2S or overexpression of the H2S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H2S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H2S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE–/– mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H2S; replacement of H2S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H2S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H2S catabolism form a positive feed-forward cycle. H2S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.

Hydrogen sulfide (H₂S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H₂S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H₂S and NO exert their effects via separate pathways, the results of the current study show that H₂S and NO are mutually required to elicit angiogenesis and vasodilatation. Exposure of endothelial cells to H₂S increases intracellular cyclic guanosine 5'-monophosphate (cGMP) in a NO-dependent manner, and activated protein kinase G (PKG) and its downstream effector, the vasodilator-stimulated phosphoprotein (VASP). Inhibition of endothelial isoform of NO synthase (eNOS) or PKG-I abolishes the H₂S-stimulated angiogenic response, and attenuated H₂S-stimulated vasorelaxation, demonstrating the requirement of NO in vascular H₂S signaling. Conversely, silencing of the H₂S-producing enzyme cystathionme-γ-lyase abolishes NO-stimulated cGMP accumulation and angiogenesis and attenuates the acetylcholine-induced vasorelaxation, indicating a partial requirement of H₂S in the vascular activity of NO. The actions of H₂S and NO converge at cGMP; though H₂S does not directly activate soluble guanylyl cyclase, it maintains a tonic inhibitory effect on PDE5, thereby delaying the degradation of cGMP. H₂S also activates PI3K/Akt, and increases eNOS phosphorylation at its activating site S1177. The cooperative action of the two gasotransmitters on increasing and maintaining intracellular cGMP is essential for PKG activation and angiogenesis and vasorelaxation. H₂S-induced wound healing and microvessel growth in matrigel plugs is suppressed by pharmacological inhibition or genetic ablation of eNOS. Thus, NO and H₂S are mutually required for the physiological control of vascular function.