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BACKGROUND: Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Tocolytics are drugs used to inhibit uterine contractions in cases of imminent preterm birth, however, few are effective in stopping labour once initiated and all have side effects. Combination approaches involving drugs that target multiple signalling pathways that regulate contractions may increase efficacy, reduce dosage and improve tolerability. Both non-steroidal anti-inflammatory drugs (NSAIDs) and hydrogen sulphide (H2S)-releasing compounds can reduce myometrial contractions. In a novel approach we evaluated the tocolytic properties of ATB-346-a H2S-releasing derivative of the NSAID naproxen, shown clinically to reduce pain and inflammation in arthritis. METHODS: Using organ baths, paired strips of human myometrium were exposed to increasing concentrations of ATB-346, or equimolar concentrations (10µM and 30µM) of the parent drug, naproxen, or the H2S-releasing moiety, 4-hydroxy-thiobenzamide (TBZ), alone. The ability of ATB-346 versus the individual components of ATB-346 to decrease ex vivo spontaneous contractions was investigated, and the potency was compared to a known H2S donor, Na2S. RESULTS: Acute application of Na2S produced a concentration-dependent decrease in force amplitude and force integral (area under the curve) of contraction. ATB-346 produced a more profound decrease in contraction compared to equimolar concentrations of naproxen or TZB alone and was more potent than the equivalent concentration of Na2S. CONCLUSIONS: ATB-346 exhibits potent tocolytic properties in human myometrium. These exciting results call for further exploration of ATB-346, with a view to repurposing this or similar drugs as novel therapies for delaying preterm labour.

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The detection of dimethyl sulphide (DMS) at levels between ppb and ppm is a significant area of research due to the necessity of monitoring the presence of this gas in a variety of environments. These include environmental protection, industrial safety and medical diagnostics. Issues related to certain uncertainties concerning the influence of high humidity on DMS measurements with resistive gas sensors, e.g., in the detection of this marker in exhaled air, of the still unsatisfactory lower detection limit of DMS are the subject of intensive research. This paper presents the results of modifying the composition of the ZnO-based sensor layer to develop a DMS sensor with higher sensitivity and lower detection limit (LOD). Improved performance was achieved by using ZnO in the form of hexagonal nano- and microplates doped with gold nanoparticles (0.75 wt.%) and by using a well-proven sepiolite-based passive filter. The modification of the layer composition with respect to the authors' previous studies contributed to the development of a sensor that is highly sensitive to 1 ppm DMS (S = 11.4) and achieves an LOD of up to 406 ppb, despite the presence of a high water vapour content (90% RH) in the analysed atmosphere.

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Plants regulate gas exchange with the environment and modulate transpirational water flow through guard cells, which set the aperture of the stomatal pores. External and internal stimuli are detected by guard cells and integrated into a signalling network that modulate turgor pressure and, hence, pore size. Pathogen-associated molecular patterns are among the stimuli that induce stomatal closure, to prevent pathogen entry through the pores, and this response, also referred to as stomatal immunity, is one of the hallmarks of PAMP-triggered immunity. While reactive oxygen species (ROS)-mediated signalling plays a key role in stomatal immunity, also the gasotransmitter hydrogen sulphide (H2S) interacts with key components of the guard cell signalling network to induce stomatal closure. While the role of H2S, produced by the main cytosolic source L-cysteine desulfhydrase 1, has been already investigated, there are additional enzymatic sources that synthesize H2S in different subcellular compartments. Their function has remained enigmatic, however. In this work, we elucidate the involvement of the mitochondrial H2S source, ß-cyanoalanine synthase CAS-C1, on stomatal immunity induced by the bacterial PAMP flagellin (flg22). We show that cas-c1 plants are impaired to induce flg22-triggered stomatal closure and apoplastic ROS production, while they are more susceptible to bacterial surface inoculation. Moreover, mitochondrial H2S donor AP39 induced stomatal closure in an RBOHD-dependent manner, while depletion of endogenous H2S, impaired RBOHD-mediated apoplastic ROS production. In addition, pharmacological disruption of mitochondrial electron transport chain activity, affected stomatal closure produced by flg22, indicating its participation in the stomatal immunity response. Our findings add evidence to the emerging realization that intracellular organelles play a decisive role in orchestrating stomatal signalling and immune responses and suggest that mitochondrial-derived H2S is an important player of the stomatal immunity signalling network.

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Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial "stunning", arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation.

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Plant survival to a potential plethora of diverse environmental insults is underpinned by coordinated communication amongst organs to help shape effective responses to these environmental challenges at the whole plant level. This interorgan communication is supported by a complex signal network that regulates growth, development and environmental responses. Nitric oxide (NO) has emerged as a key signalling molecule in plants. However, its potential role in interorgan communication has only recently started to come into view. Direct and indirect evidence has emerged supporting that NO and related species (S-nitrosoglutathione, nitro-linolenic acid) are mobile interorgan signals transmitting responses to stresses such as hypoxia and heat. Beyond their role as mobile signals, NO and related species are involved in mediating xylem development, thus contributing to efficient root-shoot communication. Moreover, NO and related species are regulators in intraorgan systemic defence responses aiming an effective, coordinated defence against pathogens. Beyond its in planta signalling role, NO and related species may act as ex planta signals coordinating external leaf-to-leaf, root-to-leaf but also plant-to-plant communication. Here, we discuss these exciting developments and emphasise how their manipulation may provide novel strategies for crop improvement.

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Hydrogen sulfide (H2S) has traditionally been considered an environmental toxin for animal lineages; yet, it plays a signaling role in various processes at low concentrations. Mechanisms controlling H2S in animals, especially in sulfide-rich environments, are not fully understood. The main detoxification pathway involves the conversion of H2S into less harmful forms, through a mitochondrial oxidation pathway. The first step of this pathway oxidizes sulfide and reduces ubiquinone (UQ) through sulfide-quinone oxidoreductase (SQRD/SQOR). Because H2S inhibits cytochrome oxidase and hence UQ regeneration, this pathway becomes compromised at high H2S concentrations. The free-living nematode Caenorhabditis elegans feeds on bacteria and can face high sulfide concentrations in its natural environment. This organism has an alternative ETC that uses rhodoquinone (RQ) as the lipidic electron transporter and fumarate as the final electron acceptor. In this study, we demonstrate that RQ is essential for survival in sulfide. RQ-less animals (kynu-1 and coq-2e KO) cannot survive high H2S concentrations, while UQ-less animals (clk-1 and coq-2a KO) exhibit recovery, even when provided with a UQ-deficient diet. Our findings highlight that sqrd-1 uses both benzoquinones and that RQ-dependent ETC confers a key advantage (RQ regeneration) over UQ in sulfide-rich conditions. C. elegans also faces cyanide, another cytochrome oxidase inhibitor, whose detoxification leads to H2S production, via cysl-2. Our study reveals that RQ delays killing by the HCN-producing bacteria Pseudomonas aeruginosa PAO1. These results underscore the fundamental role that RQ-dependent ETC serves as a biochemical adaptation to H2S environments, and to pathogenic bacteria producing cyanide and H2S toxins.

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The technical feasibility of leaching antimony from an antimony-bearing copper sulphide concentrate, using alkaline sulphide solutions and microwave-assisted and non-assisted heating technology, is investigated at a laboratory scale. The leaching test examines the influence of selective leaching reagent (Na2S and NaOH) concentrations, solid/liquid ratio, and temperature. The results indicate that antimony dissolution is highly selective (e.g. only Sb and As are leached), depending on the concentrations of leaching reagents and the leaching temperature. The influence of temperature on the mineral's dissolution, in the range 25-140 °C, is analysed from a thermochemical point of view using equilibrium databases. Under the optimal conditions: leaching agent: 250 g/L Na2S, 60 g/L NaOH, 2 h, 140 °C, with microwave assisted, the leaching efficiency of Sb reached 95.7 %. The antimony content in the copper concentrate is successfully reduced from 1.1 wt% to <0.2 wt% Sb, making it suitable for copper concentrate metallurgical processing. The study demonstrates that increasing temperature and NaOH/Na2S concentrations collectively enhance leaching efficiency, with a statistical significance, reducing both leaching time and the required temperature, compared to non-microwave-assisted leaching. Furthermore, it is established that excess free hydrogen sulphide ions ensure the efficient dissolution of the main impurities associated with penalties, such as antimony and arsenic, with limited copper and iron dissolution from the copper concentrate, predominantly chalcopyrite. Finally, an integrated hydrometallurgical process flowsheet for antimony removal and recovery from a sulphide copper concentrate is proposed.

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Hydrogen sulphide (H2S) is required for optimal establishment of soybean (Glycine max)-Sinorhizobium fredii symbiotic interaction, yet its role in regulating the nitrogen fixation-senescence transition remains poorly understood. A S. fredii cystathionine γ-lyase (CSE) mutant deficient in H2S synthesis showed early nodule senescence characterized by reduced nitrogenase activity, structural changes in nodule cells, and accelerated bacteroid death. In parallel, the CSE mutant facilitated the generation of reactive oxygen species (ROS) and elicited antioxidant responses. We observed that H2S-mediated persulfidation of cysteine C31/C80 in ascorbate peroxidase (APX) and C32 in APX2 modulated enzyme activity, thereby participating in hydrogen peroxide (H2O2) detoxification and delaying nodule senescence. Comparative transcriptomic analysis revealed a significant up-regulation of GmMYB128, an MYB transcription factor (TF), in the CSE mutant nodules. Functional analysis through overexpression and RNAi lines of GmMYB128 demonstrated its role as a positive regulator in nodule senescence. MYB128-OE inoculated with the CSE mutant strain exhibited a reduction in nitrogenase activity and a significant increase in DD15 expression, both of which were mitigated by NaHS addition. Changes at the protein level encompassed the activation of plant defenses alongside turnover in carbohydrates and amino acids. Our results suggest that H2S plays an important role in maintaining efficient symbiosis and preventing premature senescence of soybean nodules.

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Electron energy loss spectra collected from fresh and corroded silver nanoparticles are compared with those from a number of reference materials, focusing on the M4,5 edge. Chemical shifts and changes in the energy loss near edge structure (ELNES) are described and found to be sufficient to distinguish metallic silver from chemically oxidised silver. The measurements, in conjunction with electron energy loss spectrum imaging, are used to assess the mechanisms for atmospheric corrosion of silver nanoparticles. We unambiguously assign the corrosion product under atmospheric conditions to be silver sulphide, but show the reaction process to be distinctly inhomogeneous, producing a variety of types of corroded particles. LAY DESCRIPTION: >Here, we use analytical electron microscopy to track the corrosion of silver nanoparticles and present chemical maps of the corrosion products. We show clear spectroscopic differences between metallic and corroded silver using the M4,5 electron energy loss spectral feature, which is not commonly studied. Our study shows that corrosion is due to interactions with sulphur in the atmosphere; and the corrosion is not uniform, but appears to develop from specific points on the surface of the nanoparticles.

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The low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.

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BACKGROUND AND PURPOSE: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. EXPERIMENTAL APPROACH: Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols. KEY RESULTS: SGLT2i treatment improved E/e' ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end-diastolic function (E/e' ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow-up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology. CONCLUSIONS AND IMPLICATIONS: SGLT2i monotherapy remediated pathological complications exhibited by two well-established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow-up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.

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AIM: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulphide (H2S) exerts a protective effect in renal IRI. The present study was carried out to investigate the effects of exogenous H2S on renal IRI by regulating autophagy in mice. METHODS: Mice were randomly assigned to control, IRI and NaHS (an H2S donor, 28, 56 and 100 µmol/kg) groups. Renal IRI was induced by clamping the bilateral renal pedicles with non-traumatic arterial clamp for 45 min and then reperfused for 24 h. Mice were administered intraperitoneally with NaHS 20 min prior to renal ischemia. Sham group mice underwent the same procedures without clamping. Serum and kidney tissues were harvested 24 h after reperfusion for functional, histological, oxidative stress, and autophagic determination. RESULTS: Compared with the control group, the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), the protein levels of LC3II/I, Beclin-1 and P62, as well as the number of autophagosomes were significantly increased, but the activity of superoxide dismutase (SOD) was decreased after renal IRI. NaHS pre-treatment dramatically attenuated renal IRI-induced renal dysfunction, histological changes, MDA concentration and p62 expression in a dose-dependent manner. However, NaHS increased the SOD activity and the protein levels of LC3II/I and Beclin-1. CONCLUSION: These results indicate that exogenous H2S protects the kidney from IRI through enhancement of autophagy and reduction of oxidative stress. Novel H2S donors could be developed in the treatment of renal IRI.

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Capitellacin (1) is a 20-residue antimicrobial ß-hairpin, produced by the marine polychaeta (segmented worms) Capitella teletai. Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin's structure-activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library of capitellacin analogues was prepared to systematically study the influence of the two disulphide bridges on its structure and activity, and their replacement with a vinyl sulphide as a potential bioisostere. Upon studying the resulting peptides' antimicrobial activity and secondary structure, the most terminal disulphide emerged as the most critical element for maintaining both bioactivity and the secondary structure, properties which were demonstrated to be closely interlinked. The removal of the innermost disulphide bridge or disulphide replacement with a vinyl sulphide emerged as strategies with which to tune the activity spectrum, producing selectivity towards E. coli. Additionally, an enantiomeric d-capitellacin analogue revealed mechanistic insights, suggesting that chirality may be an inherent property of capitellacin's bacterial membrane target, or that a hitherto unknown secondary mechanism of action may exist. Additionally, we propose the Alloc protecting group as a more appropriate alternative to the common Dde group during fast-flow Fmoc-SPPS, in particular for short-chain diamino acids.

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During the production and laying phases of hot-mixing asphalt (HMA), various volatile organic compounds (VOCs) and noxious gases such as H2S are released into the atmosphere. These emissions are a serious environmental problem, a risk to human health, and expose workers and residents to unfriendly odours. The aim of this study was the development of a fast and sensitive analytical method to detect the H2S emitted from hot bituminous binder that is generally used in the various stages of asphalt production, processing, handling and during road construction. The method consisted in the analysis of evolved H2S from a flask with molten bitumen, using nitrogen as a carrier gas to lead the volatile compounds into a residual gas analyser equipped with a quadrupole mass spectrometer. The analysis was performed following the H2S-specific signals at m/z 33 (HS+) and at m/z 34 (H2S+) in real time, directly on the sample without laborious and expensive pre-treatments and with short response times (<6 s). Calibration with a standard mixture of 1000 ppm of H2S in nitrogen allows semi-quantitative H2S detection. The sensitivity and rapidity of the method were evaluated by quenching the release of sulphur compounds with commercial odour-suppressing agents. Upon addition of 0.1% of additive in two minutes, the H2S signal drops about 80% in two minutes, confirming the good response of the method, even with a very complex matrix.

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Hydrogen sulphide (H2S) is considered an immunotoxicant, and its presence in the water can influence the mucosal barrier functions of fish. However, there is a significant knowledge gap on how fish mucosa responds to low environmental H2S levels. The present study investigated the consequences of prolonged exposure to sub-lethal levels of H2S on the mucosal defences of Atlantic salmon (Salmo salar). Fish were continuously exposed to two levels of H2S (low: 0.05 µM; and high: 0.12 µM) for 12 days. Unexposed fish served as control. Molecular and histological profiling focused on the changes in the skin, gills and olfactory rosette. In addition, metabolomics and proteomics were performed on the skin and gill mucus. The gene expression profile indicated that the gills and olfactory rosette were more sensitive to H2S than the skin. The olfactory rosette showed a dose-dependent response, but not the gills. Genes related to stress responses were triggered at mucosal sites by H2S. Moreover, H2S elicited strong inflammatory responses, particularly in the gills. All mucosal organs demonstrated the key molecular repertoire for sulphide detoxification, but their temporal and spatial expression was not substantially affected by sub-lethal H2S levels. Mucosal barrier integrity was not considerably affected by H2S. Mucus metabolomes of the skin and gills were unaffected, but a matrix-dependent response was identified. Comparing the high-concentration group's skin and gills mucus metabolomes identified altered amino acid biosynthesis and metabolism pathways. The skin and gill mucus exhibited distinct proteomic profiles. Enrichment analysis revealed that proteins related to immunity and metabolism were affected in both mucus matrices. The present study expands our knowledge of the defence mechanisms against H2S at mucosal sites in Atlantic salmon. The findings offer insights into the health and welfare consequences of sub-lethal H2S, which can be incorporated into the risk assessment protocols in salmon land-based farms.

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This study investigates the utilization of carbon dots (CDs) from neem leaves (Azadirachta indica) decorated onto cadmium sulfide (CdS) for the photocatalytic degradation of ciprofloxacin. A comparative study of ciprofloxacin degradation with pristine CdS and CD decorated CdS demonstrated high degradation of âˆ¼ 75 % with CD/CdS when compared to bare CdS (∼68 %). Process optimization studies were further carried out with CD/CdS catalysts at different solution pH (4-10), feed concentrations (10-50 mg/L), catalyst loadings (25-125 mg/L), temperatures (10 - 30 °C), and lamp power (25, 50, 250 W and sunlight). Higher temperatures, combined with a solution pH of 7 and catalyst loading of 100 mg/L favored the enhanced degradation of 20 mg/L of ciprofloxacin. The ciprofloxacin degradation rate increased linearly with temperature with an apparent activation energy of 27 kJ mol-1. The CD/CdS photocatalyst demonstrated maximum degradation rates with higher lamp powers while it also showed remarkable performance under natural sunlight achieving the same degradation within 3 h.

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The detection of ampicillin plays a crucial role in managing and monitoring its usage and resistance. This study introduces a simple and effective biosensor for ampicillin detection, utilizing the unique absorbance features of Mn-doped ZnS capped by chitosan micromaterials in conjunction with ß-lactamase activity. The biosensors can detect ampicillin concentrations from 13.1 to 72.2 µM, with a minimum detection limit of 2.93 µM for sensors based on 300 mg/L of the sensing material. In addition, these sensors show high specificity for ampicillin over other antibiotics such as penicillin, tetracycline, amoxicillin, cephalexin, and a non-antibiotic-glucose. This specificity is demonstrated by an enhancing effect when beta-lactamase is used, as opposed to a quenching effect observed at 340 nm in the absorbance spectrum when no beta-lactamase is present. This research highlights the potential of affordable chitosan-capped Mn-doped ZnS micromaterials for detecting ampicillin through simple absorbance measurements, which could improve the monitoring of antibiotics in both clinical and environmental settings.

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Introduction: Therapies targeting histone deacetylase (HDAC) have gained wider attention in the treatment of various clinical conditions. However, the use of HDAC inhibitors in pre-clinical trials in the case of Parkinson's disease (PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was tested in animals induced with Parkinson's disease experimentally. Material and methods: Wistar male rats (150 ±10 g) were administered with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat (20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD markers, and HDACs were analysed in the control and experimental animals. Results: The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control cells. Moreover, the induction of PD in rats demonstrated reduced levels of H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3 and NMDA2b were reduced, with a significant increase in neuroprotective genes such as VDAC3 and CBX5 in entinostat-supplemented rats. Conclusions: The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of treatment in PD.

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Although marine environments represent huge reservoirs of the potent greenhouse gas methane, they currently contribute little to global net methane emissions. Most of the methane is oxidized by methanotrophs, minimizing escape to the atmosphere. Aerobic methanotrophs oxidize methane mostly via the copper (Cu)-bearing enzyme particulate methane monooxygenase (pMMO). Therefore, aerobic methane oxidation depends on sufficient Cu acquisition by methanotrophs. Because they require both oxygen and methane, aerobic methanotrophs reside at oxic-anoxic interfaces, often close to sulphidic zones where Cu bioavailability can be limited by poorly soluble Cu sulphide mineral phases. Under Cu-limiting conditions, certain aerobic methanotrophs exude Cu-binding ligands termed chalkophores, such as methanobactin (mb) exuded by Methylosinus trichosporium OB3b. Our main objective was to establish whether chalkophores can mobilise Cu from Cu sulphide-bearing marine sediments to enhance Cu bioavailability. Through a series of kinetic batch experiments, we investigated Cu mobilisation by mb from a set of well-characterized sulphidic marine sediments differing in sediment properties, including Cu content and phase distribution. Characterization of solid-phase Cu speciation included X-ray absorption spectroscopy and a targeted sequential extraction. Furthermore, in batch experiments, we investigated to what extent adsorption of metal-free mb and Cu-mb complexes to marine sediments constrains Cu mobilisation. Our results are the first to show that both solid phase Cu speciation and chalkophore adsorption can constrain methanotrophic Cu acquisition from marine sediments. Only for certain sediments did mb addition enhance dissolved Cu concentrations. Cu mobilisation by mb was not correlated to the total Cu content of the sediment, but was controlled by solid-phase Cu speciation. Cu was only mobilised from sediments containing a mono-Cu-sulphide (CuSx) phase. We also show that mb adsorption to sediments limits Cu acquisition by mb to less compact (surface) sediments. Therefore, in sulphidic sediments, mb-mediated Cu acquisition is presumably constrained to surface-sediment interfaces containing mono-Cu-sulphide phases.

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INTRODUCTION: Manic depressive psychosis (MDP) or bipolar disorder, a prevalent psychiatric condition globally and in the Indian population, has been attributed to various pathological mechanisms. Hydrogen sulphide (H2S), a member of the gasotransmitter family, may be linked to the development of bipolar disorder because it plays a crucial role in maintaining proper neuronal function in terms of excitability, plasticity, and homeostatic functions. There is very little data regarding the role of the gasotransmitter H2S in MDP in terms of its association, diagnostic ability, and severity prediction, which led us to conduct this study among MDP patients in the Sub-Himalayan region of West Bengal. METHODS: This was an observational case-control study performed in the Department of Biochemistry, North Bengal Medical College and Hospital, Siliguri, West Bengal, India, from January 2022 to December 2022. Fifty diagnosed MDP patients and 50 healthy age- and sex-matched control subjects satisfying the inclusion and exclusion criteria were studied. The H2S level in the blood was assayed using the standardised spectrophotometric methylene blue method. The severity of depression was assessed by Hamilton Depression Rating Scale (HAM-D) scoring. RESULTS: Of the 50 MDP patients, 45 (90%) were in the depressive phase, and five (10%) were in the manic phase. Of the 45 depressive patients, eight (17.8%) had mild depression, 12 (26.7%) had moderate depression, 19 (42.2%) had severe depression, and six (13.3%) had very severe depression. The mean H2S level in MDP patients (41.98±18.88 µmol/l) was significantly (P<0.05) lower than that in control subjects (99.20± 15.20 µmol/l). It was also observed that the mean H2S level in MDP patients decreased with the duration of the disease but was not statistically significant. The mean H2S levels in the different depression severity groups were found to be significantly different (P<0.001). Receiver operating characteristic (ROC) curve analysis revealed that a cut-off value of H2S <78.5 µmol/l was associated with MDP, with a sensitivity of 96% and a specificity of 88%, and a cut-off value of H2S < 53 µmol/l predicted the severity of depression with a sensitivity of 89.3% and a specificity of 76.5%. CONCLUSION: The significant association of the gasotransmitter H2S in MDP patients and its role as a diagnostic and severity predictive marker can help us to employ proper measures for better management of MDP and improving quality of life.