How Viscous Is the Solidlike Structure at the Interface of Ionic Liquids? A Study Using Total Internal Reflection Fluorescence Spectroscopy with a Fluorescent Molecular Probe Sensitive to High Viscosity

Aiming at the evaluation of the viscosity of the interfacial solidlike structure of ionic liquids (ILs), we performed total internal reflection fluorescence (TIRF) spectroscopy for N, N-diethyl-N′-phenyl-rhodamine (Ph-DER), a fluorescent probe that is sensitive to viscosity in a high-viscosity range. TIRF spectra at the glass interface of trioctylmethylammonium bis(nonafluorobutanesulfonyl)amide (TOMAC4C4N), a hydrophobic IL, showed that the fluorescence intensity of Ph-DER increases with the decrease of the evanescence penetration depth, suggesting that there exists a high-viscosity region at the interface. In contrast, glycerol, which is a molecular liquid with a bulk viscosity similar to that of TOMAC4C4N, did not show such a fluorescence increase, supporting that the formation of a highly viscous solidlike structure at the interface is intrinsic to ILs. A model analysis suggested that the high viscous region at the glass interface of TOMAC4C4N is at least twice thicker than the ionic multilayers at the air interface, implying that the solid substrate enhances the ordering of the interfacial structure of ILs. The viscosity at the glass interface of TOMAC4C4N was found to be at least 40 times higher than that of the liquid bulk

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy

Sulfide Catabolism Ameliorates Hypoxic Brain Injury

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury

Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules

Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-Sn-S-R), hydrogen polysulfides (H2Sn), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required. Classically, sulfane sulfur compounds can be detected by cyanolysis, involving nucleophilic attack by cyanide ion to cleave the sulfur–sulfur bonds. The generated thiocyanate reacts with ferric ion, and the resulting ferric thiocyanate complex can be easily detected by absorption spectroscopy. Recent exploration of the properties of sulfane sulfur compounds as both nucleophiles and electrophiles has led to the development of various chemical techniques for detection, isolation, and bioimaging of sulfane sulfur compounds in biological samples. These include tag-switch techniques, LC-MS/MS, Raman spectroscopy, and fluorescent probes. Herein, we present an overview of the techniques available for specific detection of sulfane sulfur species in biological contexts

A Single Fluorescent Probe to Visualize Hydrogen Sulfide and Hydrogen Polysulfides with Different Fluorescence Signals

As climate change and fossil fuel extractive industries ravage Indian country and burden many Indigenous communities with risks, the negative impacts on tribal sovereignty, health, and cultural resources demand consultation between tribes and the federal government. Yet, this is an area where the law fails to provide adequate guidance to parties who should be engaging or are already engaging in tribal consultations. The law, both domestic and international, may require that consultation occurs, but leaves parties to determine themselves what constitutes effective and efficient consultation. The legacy of the law’s inability to provide effective guidance has generated a litany of cases of litigation and mutual hard feelings, a glaring example being how the legitimacy consultative activities was debated and misunderstood in the Standing Rock Tribe’s resistance against the Dakota Access Pipeline. This article hopes to fill the void by turning to other disciplines – ethics and Indigenous studies, for guidance on how effective consultation may be achieved.To accomplish this, the article begins with an examination of relevant domestic and international law. While true that claims exist under both domestic and possibly international law to require the federal government to engage in government-to-government consultation with tribes, very little guidance is given as to what that consultation should look like and which sovereign, whether the tribe or the federal government, gets to dictate the process of consultation. Further, existing domestic and international law provides little as to the scope of such consultation or when it is triggered. Given the law’s inability to fully answer the question of what effective consultation looks like, the article suggests that ethics and morality literature, especially the literature emerging from Indigenous studies, is helpful in framing normative judgments regarding effective consultation.From a moral perspective, consultation can be linked to the norm that all parties should have a chance to give their free, prior and informed consent to the actions of any other party whose actions may impact them in some way. Impacts include harms or opportunities to share in any future benefits. In the literature on ethics, “free,” “prior” and “informed” consent are taken as being defined in certain ways. While there are a range of legal and other purposes for consultation, morally speaking, consultation can be understood as one process or strategy for fulfilling the general moral duty of consent. Further, emerging Indigenous studies literatures pertaining to ethics add additional moral requirements to these definitions.The idea of consent, as a moral norm, suggests a relationship between the U.S., tribes, and other parties that would flow much more like a partnership than a formal consultation, and where tribes would have veto rights (the right to say “no”) to any actions that would impact them. To demonstrate this concept, the article presents two examples: the Dakota Access pipeline controversy, an example of ineffective consultation, and the Northwest Forest Plan, an example of deliberate approaches to monitor the effectiveness of consultation. Based on these examples combined with the ethics literature, the article concludes with specific strategies that parties might employ to ensure successful tribal consultations. Beyond filling the void created by current federal law, the article therefore constitutes a valuable and unique addition to the existing scholarship in its interdisciplinary approach, and guidance to parties engaged in tribal consultations

Azobenzene-caged sulforhodamine dyes: A novel class of 'turn-on' reactive probes for hypoxic tumor cell imaging

International audienceNew sulforhodamine-based fluorescent 'turn-on' probes have been developed for the direct imaging of cellular hypoxia. Rapid access to this novel class of water-soluble 'azobenzene-caged' fluorophores was made possible through an easily-implementable azo-coupling reaction between a fluorescent primary arylamine derived from a sulforhodamine 101 scaffold (named SR101-NaphtNH 2 ) and a tertiary aniline whose N-substituents are neutral, cationic, or zwitterionic. The detection mechanism is based on the bioreductive cleavage of the azo bond that restores strong far-red fluorescence (emission maximum at 625 nm) by regenerating the original sulforhodamine SR101-NaphtNH 2 . This valuable fluorogenic response was obtained for the three 'smart' probes studied in this work, as shown by an in vitro assay using rat liver microsomes placed under aerobic and then under hypoxic conditions. Most importantly, the probe namely SR101-NaphtNH 2 -Hyp-diMe was successfully applied for imaging the hypoxic status of tumor cells (A549 cells)

Sodium Thiosulfate Attenuates Acute Lung Injury in Mice

BACKGROUND: Acute lung injury (ALI) is characterized by neutrophilic inflammation and increased lung permeability. Thiosulfate is a stable metabolite of hydrogen sulfide, a gaseous mediator that exerts anti-inflammatory effects. While sodium thiosulfate (STS) has been used as an antidote, the effect of STS in ALI is unknown. We assessed the effects of STS in mice lung and vascular endothelial cells subjected to acute inflammation. METHODS: Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide or subjected to cecal ligation and puncture with or without STS. Effects of STS on endothelial permeability, and the production of inflammatory cytokines and reactive oxygen species were examined in cultured endothelial cells incubated with lipopolysaccharide or tumor necrosis factor alpha (TNFα). Levels of sulfide and sulfane sulfur were measured using novel fluorescence probes. RESULTS: STS inhibited lipopolysaccharide-induced production of cytokines (Interleukin-6 (pg/ml); 313±164, lipopolysaccharide; 79±27, lipopolysaccharide + STS (n=10)), lung permeability, histological lung injury, and nuclear factor-κB activation in the lung. STS also prevented upregulation of Interleukin-6 in the mouse lung subjected to cecal ligation and puncture. In endothelial cells, STS increased intracellular levels of sulfide and sulfane sulfur, inhibited lipopolysaccharide or TNFα-induced production of cytokines and reactive oxygen species. The beneficial effects of STS were associated with attenuation of the lipopolysaccharide-induced nuclear factor-κB activation through the inhibition of TNF receptor-associated factor 6 ubiquitination. CONCLUSIONS: STS exerts robust anti-inflammatory effects in mice lung and vascular endothelium. Our results suggest a therapeutic potential of STS in ALI