Redox Changes Research Articles

12362 Pathophysiology From Oxidative Stress Effectively Monitored In A Pre-clinical Model Of Type 2 Diabetes (T2D) With Point-of-care Microscale Magnetic Resonance (µNMR)

Abstract Disclosure: A.T. Alves: ; Co-Founder. ; Self. ; LarmorBio. S.S. Thamarath: ; Co-Founder. ; Self. ; LarmorBio. S. Fjordside: Employee; Self; Novo Nordisk. S. Sassower, MS.EE: ; Co-Founder. ; Self. ; LarmorBio. J. Han: None. L. Bouchard: Advisory Board Member; Self; LarmorBio. R. Rohr, BS.EE: ; Co-Founder, CEO. ; Self. ; LarmorBio. A.P. Chambers: Employee; Self; Novo Nordisk. The declining age of onset of T2D is a vital factor influencing its prospective burden. An early manifestation of the disease leads to an extended duration, which amplifies and accelerates the risk of micro and macrovascular complications. Oxidative stress is a major driver in the pathogenesis of T2D. Early detection and prevention of oxidative stress overload can improve and potentially modify the long-term harmful outcomes of metabolic diseases, including chronic hyperglycaemia.A novel µNMR assay was developed to monitor oxidative stress from minimally invasive plasma samples at the point of care. This approach is highly sensitive to redox changes in the blood microenvironment, including increased ferric iron (Fe3+), protein oxidation, and lipid peroxidation[1]. We hypothesized that oxidative stress would increase significantly faster in the disease group, enabling disease progression monitoring throughout the study and near real-time subject risk stratification based on the core pathophysiology of the diabetic phenotype.This 15-week longitudinal study (6th - 21st week of age) quantified oxidative stress in db/db and db/+ mice (n = 15 per group), accompanied by HbA1c, blood glucose (BG), and body weight (BW). The assay detailed separation (P ≤ 0.01) between the db/db and db/+ mice from the onset of the diabetic phenotype of db/db at 10 weeks of age (mean HbA1c = 6.5%). The oxidative stress monitored continued to increase in the subsequent weeks, where the HbA1c of db/db mice reached maximum (mean HbA1c = 8.8%). The definition of good (HbA1c ≤ 8) and poor (HbA1c > 8) glycaemic control was defined where sub-stratification (P ≤ 0.05) was achieved. Furthermore, the assay highlights a positive correlation with BW (ρ+/db = 0.52, P ≤ 0.0001, ρdb/db = 0.57, P ≤ 0.0001). In the two groups of mice, a positive correlation of oxidative stress with HbA1c (ρ = 0.58, P ≤ 0.0001) and BG (ρ = 0.47, P ≤ 0.0001) was reported. During the 15-week study, the control db/+ group exhibited a 13% mean increase in oxidative stress. In contrast, the db/db group demonstrated a cumulative 20% increase. Notably, considering the diabetic phenotype of the db/db mice, we quantified oxidative stress attributed to aging at 13%.In view of changing diabetes demographics, a multimodal approach of targeted sub-phenotype treatment combined with advanced metabolic monitoring may provide holistic, clinically relevant information to reduce the micro and macrovascular burden of diabetes. In summary, the µNMR assay is an effective method for real-time monitoring of oxidative stress assessment in metabolic disease research and opens new possibilities for cardiometabolic risk assessment and targeted interventions.(1) Peng, W.K. et.al., npj Aging Mech Dis 2020, 6, 11 Presentation: 6/1/2024

12380 Point Of Care Microscale Magnetic Resonance (µNMR) Effectively Monitors Mitigation Of Oxidative Stress By GLP-1 Treatment In A Preclinical Model Of Diabetic Nephropathy

Abstract Disclosure: A.T. Alves: ; co-founder. ; LarmorBio. S.S. Thamarath: ; co-founder. ; LarmorBio. S. Fjordside: Employee; Self; Novo Nordisk. S. Sassower, MS.EE: ; Co-founder. ; LarmorBio. R. Rohr: ; co-founder,CEO. ; LarmorBio. A.P. Chambers: Employee; Self; Novo Nordisk. Oxidative stress is a major driver in the pathogenesis of diabetes, obesity, and related (cardio-renal) disorders. Early detection and prevention of an oxidative stress overload can improve and potentially modify the long-term harmful outcomes associated with chronic hyperglycaemia. A novel assay was developed, that uses µNMR technology to directly monitor oxidative stress from 5 µL of plasma at the point of collection in less than 10 minutes. This assay is highly sensitive to redox changes in the blood microenvironment, including increased ferric iron (Fe3+), protein oxidation and lipid peroxidation. Here, we show the oxidative stress profiling of three groups of ZSF1 rats in a twelve week (11th -23rd week of age) observational study. Vehicle lean, vehicle obese, and glucagon-like-peptide-1 (GLP-1) treated obese ZSF1 rats (n = 8/group) were studied with the assay along with conventional diabetic/metabolic markers, blood glucose (BG), HbA1c, Albumin Creatinine Ratio (ACR). The kidney (immuno)histology studies, alpha-smooth muscle actin (aSMA) and leucocyte common antigen (CD45) were performed at the termination phase of the ZSF1 rats (23rd week of age). The results demonstrated that the assay distinguished obese rats from lean rats with statistical significance (P ≤ 0.01) independent of other in-life diabetic/metabolic markers. Significant correlations with urinary Albumin Creatinine Ratio (ACR, ρ = 0.64, P ≤ 0.0001) were established throughout the study. A positive quantitative association is highlighted with classic histological end points of organ damage, kidney fibrogenesis (aSMA, ρ = 0.23), and inflammation (CD45, ρ = 0.45). Moreover, the assay detected significantly reduced oxidative stress levels (e.g., P ≤ 0.01) in the GLP-1 drug treatment group at five weeks of follow-up. In summary, the µNMR assay effectively monitored oxidative stress and captured disease-modifying therapeutics. Presentation: 6/1/2024

Effect of peroxiredoxin 1 or peroxiredoxin 2 knockout on the thiol proteome of Jurkat cells.

Peroxiredoxins are important regulators of cellular peroxide metabolism. As antioxidants, they restrict oxidation of other cell proteins, but as signaling molecules they can act as sensors and promote thiol protein oxidation via a redox relay mechanism. The presence of peroxiredoxins could therefore influence other thiol proteins, even in cells experiencing endogenous redox activity. To investigate this for the two cytoplasmic peroxiredoxins, Prdx1 and Prdx2, we have compared the thiol proteome of wildtype Jurkat cells with cells in which either one was knocked out. Using mass spectrometry and isotope tagging, approximately 10,000 common CysSH-containing peptides were detected for each WT/KO comparison. Knockout of Prdx1 or Prdx2 resulted in a change in redox state of a small selection of Cys residues, with less than 100 giving more than a 2-fold difference. Strikingly, a large proportion of these, including those that showed the greatest change, were common to both KOs. Some Cys residues showed more oxidation in the knockouts, whereas others showed less. The candidate proteins have diverse functions and have not been known to be oxidant sensitive. No differences were seen in redox state of Cys residues of other Prdxs and oxidant sensitive proteins. A change in expression in Prdx2 knockout cells was indicated for seven cytoskeletal or regulatory thiol proteins, three of which were tested and validated by western blotting. Little firm evidence was found for thiol redox changes dependent on either Prdx that could be attributed to oxidation via a relay mechanism.

Chromium cycle in Red Soil Critical Zone constrained by chromium isotopes

Chromium (Cr) isotopic system has been used to trace Cr pollution in the modern surface environment and redox change in the paleoenvironment. However, the transformation mechanism of Cr in soil and the accompanied Cr isotopic fractionation have not been clarified clearly. Here we measured Cr isotopic compositions (δ53Cr) of two paddy field profiles from the Red Soil Critical Zone Observatory in South China. The δ53Cr values of the young paddy fields, which have been cultivated for about 20 years, range from −0.34 ‰ to −0.22 ‰. The old paddy fields have been cultivated for >100 years and have more positive Cr isotopic compositions than the young paddy fields, from −0.20 ‰ to −0.06 ‰. The results of three-step leaching experiments show that iron and manganese oxides are enriched in heavy Cr isotopes, while organic matters have much lower Cr isotopic compositions, likely resulting from back reduction of Cr(VI). Our results suggest that Cr isotopic fractionation during the oxidation of Cr(III) is not the only reason for the depletion of heavy isotopes during oxidative weathering, and the partial back-reduction of generated Cr(VI) by organic matter plays an important role in Cr isotopic fractionation during weathering. Comparison between the old and young paddy fields further indicates that cultivation can significantly affect the Cr cycle in red soils. Paddy fields could be a potential sink for the Cr(VI) contaminant, and soils with a long history of cultivation would be more susceptible.

First Insight into the Mobilization and Sequestration of Arsenic in a Karstic Soil during Redox Changes.

Karst terrains provide drinking water for about 25% of the people on our planet, particularly in the southwest of China. Pollutants such as arsenic (As) in the soil can infiltrate groundwater through sinkholes and bedrock fractures in karst terrains. Despite this, the underlying mechanisms responsible for As release from karst soils under redox changes remain largely unexplored. Here, we used multiple synchrotron-based spectroscopic analyses to explore As mobilization and sequestration in As-polluted karstic soil under biogeochemical conditions that mimic field-validated redox conditions. We observed that As in the soil exists primarily as As(V), which is mainly associated with Fe(oxyhydr)oxides. The concentration of the dissolved As was high (294 μM) and As(III) was dominant (∼95%) at low Eh (≤-100 mV), indicating the high risk of As leaching under reducing conditions. This As mobilization was attributed to the fact that the dissolution of ferrihydrite and calcite promoted the release and reduction of associated As(V). The concentration of the dissolved As was low (17.0 μM) and As(V) was dominant (∼68%) at high Eh (≥+100 mV), which might be due to the oxidation and/or sequestration of As(III) by the recrystallized ferric phase. Our results showed that the combined effects of the reductive release of As(V) from both ferric and nonferric phases, along with the recrystallization of the ferric phase, govern the redox-induced mobilization and potential leaching of As in soils within karst environments.

Tuning Energetics of 2 e-/2H+ PCET Properties with Model Ru-bisamido Complexes.

Most redox processes that break/form bonds involve net 2e- changes, and many are coupled to protons. Yet most proton-coupled electron transfer (PCET) studies focus on 1e-/1H+ reactions. Reported here is a family of molecular models that undergo tunable 2e-/2H+ redox changes. Complexes [(X2bpy)RuII(en*)2](PF6)2 and [(X2bpy)RuIV(en*-H)2](PF6)2 have been synthesized with bpy=2,2'-bipyridine with 4,4'-subtitutions X=-NMe2, -OMe, -Me, -H, -CF3; and en*=2,3-dimethyl-2,3-butanediamine. They have been characterized by IR, UV-vis, and NMR spectroscopies, XRD, electrochemistry, mass spectrometry, DFT and (TD)DFT computations. The introduction of electron-withdrawing and donating groups at the 4,4'-position of the bpy ligand affects the complexes' redox potentials, pKa's, and Bond Dissociation Free Energies (BDFEs) of the N-H bonds in the en* ligands. The average BDFEs for the overall 2e-/2H+ PCET span over 5 kcal/mol. Notably, these complexes all show marked potential inversion over an extended range, ΔpKa>25 units and ΔE0>1.4 V. Potential inversion remains despite the electronic influence of bpy's substitutions which regulate N-H properties several bonds apart by trans-effect over dπ-molecular orbitals at the Ru center. The experimental and computational results presented in this work support the presence of strong coupling between electrons and protons, for modelling insights of 2e-/2H+ transfer reactivity.

The Rise of Proterozoic Diagenetic Spheroids Formed by Chemically Oscillating Reactions and Stimulated by Environmental Redox Changes

The Rise of Proterozoic Diagenetic Spheroids Formed by Chemically Oscillating Reactions and Stimulated by Environmental Redox Changes

Volcanism and turbidity current events as drivers of the evolution of benthic redox conditions: Organic matter enrichment in the Chang 7 member, Upper Triassic Yanchang formation, Ordos Basin, North China

Depositional events have a significant impact on the terrestrial redox conditions and provide evidence for studying the organic matter enrichment. The objective of this study was to evaluate the influence of volcanic and turbidity current events on benthic redox conditions during the Upper Triassic Chang 7 member (Ch7) of the Ordos Basin. To address these issues, the varying sedimentological settings, paleoredox conditions, and relationships between the redox environment and depositional events were investigated via sedimentary analysis of the profiles, microscopic analysis, organic geochemical analysis, and elemental geochemical data. The fine-grained sediments in the Chang 73 submember (Ch73) consist of abundant organic matter, collophanite, and framboidal pyrite. However, in the upper part of the Ch7 member, there was a decrease in organic matter, a decrease in the number of microorganisms, and an increase in pyrite size, indicating that the oxic environment is not favorable for organic matter enrichment. The element and geochemical proxies show similar vertical variations and redox changes. Volcanic activity can bring substantial amounts of material or elements to the basin. The enrichment of Hg and S exhibited considerable variation, ranging from 8.7 to 274.4 ppb and from 0.16 to 4.53 wt%, respectively, which influenced the organic matter accumulation through the flourishing and death of microorganisms and redox changes in the benthic environment of the terrestrial basin. As the lake basin shrinks, the Ti and Al contents increase with increasing frequency of turbidity current events, and the terrestrial debris transported to the lake basin gradually increases while carrying large amounts of oxygen and affecting sedimentation rates, contributing to the destruction of the reducing conditions of the benthic environment, subsequently, influencing organic matter accumulation. These results will be helpful in understanding the effect of multiple depositional events on organic matter enrichment in lacustrine basins.

Exhaust purification of stoichiometric natural gas applications – A screening study on the impact of catalyst composition, reaction conditions and transient effects

A set of model catalysts with a variation of precious metal components comprising Pt, Pd or Pt/Pd on typical support materials (CeO2, Al2O3 and ZrO2) is evaluated in a gas mixture simulating the exhaust gas of stoichiometric natural gas-fueled engines. Three-way catalytic (TWC) performance, especially CH4 conversion, is assessed in λ-sweep as well as dynamic light-Off/light-Out tests, both with oscillating feed (1 s lean /1 s rich) implemented on a fully automated reactor system. The transient response of catalysts to changing redox potential is demonstrated in tests with varying lean/rich duration and pseudo-stationary tests. Time resolved data clearly indicate that performance and stability depend on both, precious metal composition as well as support material. Beyond screening of catalyst activity, the focus was on factors affecting the formation of undesired by-products (e.g. NH3, N2O) on hydrothermally aged catalysts. Aging severity was introduced as additional dimension in the design of the experimental study.

Arctic Alaska deepwater organic carbon burial and environmental changes during the late Albian–early Campanian (103–82 Ma)

The middle Cretaceous greenhouse period experienced profound environmental change including episodes of enhanced global burial of organic carbon marked by carbon isotopic excursions (CIEs). However, the role and response of polar regions like the newly formed, partially enclosed Arctic Ocean Basin during middle Cretaceous carbon burial remains enigmatic. We present the first Arctic deepwater CIE record that characterizes conditions offshore of the Alaska margin north of 75°N paleolatitude. Organic carbon isotopes (δ13Corg) and 103–82 Ma ash zircon U-Pb dates from the distal Hue Shale record multiple Albian–Campanian CIEs during slow ∼3–15 m/Myr sediment accumulation rates. Average total organic carbon (TOC) increased substantially during large 2–3 ‰ CIEs of the ∼101 Ma Albian-Cenomanian boundary event (from 7 to 18 % TOC) and ∼94 Ma Cenomanian-Turonian boundary event (5 to 10 % TOC). Turonian TOC remained elevated (8–13 %) during high global sea levels and temperatures of the Cretaceous Thermal Maximum, followed by an increase from 7 to 11 % TOC during the ∼90 Ma late Turonian event 1.5 ‰ CIE. Average TOC subsequently decreased in the Coniacian–Campanian, but relative maxima occurred during subtle 0.5–1 ‰ CIEs interpreted as the ∼87 Ma late Coniacian event (increase from 4 to 7 % TOC), ∼85 Ma Horseshoe Bay event (3.5 to 4.5 % TOC), and ∼84 Ma Santonian-Campanian boundary event (3.5 to 5 % TOC). Increases in hydrogen index and productivity proxies (P, Ba, Nd) that accompanied each CIE episode with enhanced TOC suggest a strong link between marine productivity and organic carbon burial at short-term CIE timescales. However, long-term (>5–8 Myr) changes in trace metal redox (Mo, Fe, V) and salinity (B/Ga) proxies suggest shifts in prevailing environmental conditions at timescales longer than the CIEs. Late Albian–middle Turonian marine salinity occurred during euxinic (103–98 Ma) and suboxic (98–90 Ma) conditions with deposition interpreted to have occurred within and beneath an oxygen minimum zone, respectively. In contrast, late Turonian–early Campanian (90–82 Ma) freshening and restricted euxinic basin conditions may signal the start of widespread restriction known to characterize the Paleogene Arctic. Overall, these results highlight that middle Cretaceous Arctic deepwater remained a productive marine carbon sink coupled to the global carbon cycle despite evolving Arctic greenhouse conditions.

Climatic-hydrologic influence on redox condition in the Cryogenian interglacial Nanhua Basin: Insights from the Datangpo Formation in the northwestern Yangtze Block, South China

Tracking climatic and oceanic redox changes throughout the Neoproterozoic Cryogenian is crucial to a better understanding of the coevolution of life and environment in geological history. However, the processes and driven mechanisms of redox evolution in the Cryogenian interglacial ocean still remain uncertain. Here, we present a combined study of geochemical proxies, such as paleoclimatic proxies (CIA and Zr/Al) and paleosalinity proxies (B/Ga and Sr/Ba), from the interglacial Datangpo Formation in the shallow-water Zuojiawan section exposed in the northwestern Yangtze Block, to constrain climatic and hydrologic changes on redox conditions. Our data indicate that two apparently climatic cycles from warming to cooling occurred during the deposition of the Datangpo Formation, supplementing the monotonous climatic warming in previous research during the Cryogenian interglaciation. The low B/Ga and Sr/Ba ratios throughout Datangpo Formation suggest a continuous freshwater condition, which is in contrast to a transition of marine condition to brackish condition in relatively deep-water sections. Compiled salinity reconstructions at different paleo-depths imply the salinity gradient in the Nanhua Basin with a density stratification like modern Baltic Sea, at least during the early Cryogenian interglacial period. We find that the climate-driven local riverine freshwater input may be a significant driver for maintaining long-term freshwater condition in the Zuojiawan section. Accompanied by synchronously climatic warming, the progressive desalinization with declining B/Ga and Sr/Ba ratios in the middle to upper deposition of the Datangpo Formation are probably attributed to the persistent freshwater input to a nearshore shallow-water paleogeographic setting. Combined the improving oceanic oxygenation backdrop with the elevating seawater sulfate concentration in the Nanhua Basin in this period, we conclude that the continuous dilution of seawater in the restrict (semi-) Nanhua Basin could attenuate the density stratification and enhance the vertical mixing of watermass, favoring the ventilation of deepwater and penetration of sulfate. This contribution provides a new insight for the study of salinity changes on redox conditions in the Yangtze Block during the Cryogenian interglacial period, and provides new data for supporting a systematic understanding of the evolutional mechanism of oceanic redox state.

Neoarchaean oxygen-based nitrogen cycle en route to the Great Oxidation Event.

The nitrogen isotopic composition of sedimentary rocks (δ15N) can trace redox-dependent biological pathways and early Earth oxygenation1,2. However, there is no substantial change in the sedimentary δ15N record across the Great Oxidation Event about 2.45 billion years ago (Ga)3, a prominent redox change. This argues for a temporal decoupling between the emergence of the first oxygen-based oxidative pathways of the nitrogen cycle and the accumulation of atmospheric oxygen after 2.45 Ga (ref. 3). The transition between both states shows strongly positive δ15N values (10-50‰) in rocks deposited between 2.8 Gaand 2.6 Ga, but their origin and spatial extent remain uncertain4,5. Here we report strongly positive δ15N values (>30‰) in the 2.68-Gyr-old shallow to deep marine sedimentary deposit of the Serra Sul Formation6, Amazonian Craton, Brazil. Our findings are best explained by regionally variable extents of ammonium oxidation to N2 or N2O tied to a cryptic oxygen cycle, implying that oxygenic photosynthesis was operating at 2.7 Ga. Molecular oxygen production probably shifted the redox potential so that an intermediate N cycle based on ammonium oxidation developed before nitrate accumulation in surface waters. We propose to name this period, when strongly positive nitrogen isotopic compositions are superimposed on the usual range of Precambrian δ15N values, the Nitrogen Isotope Event. We suggest that it marks the earliest steps of the biogeochemical reorganizations that led to the Great Oxidation Event.

Dual-mode iodine sensing: Colorimetric and electrochemical detection methods using functionalized gold nanoparticles

Iodine in natural and treated waters exists mainly as iodide, iodate, and molecular iodine (I2). I2 is a highly volatile and reactive species impacting biological and chemical systems. Iodine, a vital micronutrient, is essential for human and animal growth and metabolism. It also plays a crucial role in synthesising artificial adrenaline within the metabolic processes of humans and animals. It is also widely used as an antiseptic, disinfectant, and for emergency water disinfection. Moreover, iodine deficiency can result in various diseases, especially hypothyroidism and goitre. Given its critical functions, it is imperative to have a straightforward, dependable, and efficient method for monitoring iodine levels. This study introduces a simple and innovative I2 detection system based on its reactivity, toxicity, and role as an indicator of oxidative conditions in water. It operates in terms of based on optical and electrochemical signal changes, utilising the anti-aggregation mechanism of gold nanoparticles (AuNPs) and 6-mercaptohexanol (MHA) for sensitive and selective detection under mild conditions. I2 determination is achieved by observing the colour change in AuNPs, which is influenced by competitive interactions between MHA, I2, and AuNPs. The optical detection system, with its low detection limit (LOD=260 nM), is based on the straightforward observation of colour changes. On the other hand, the electrochemical detection method utilises changing redox peaks observed in anodic region, providing selective and sensitive I2 detection (LOD=100 nM). The probe effectively detects the presence of I2 in real water samples as a practical application. Moreover, the proposed method revolutionises I2 detection by incorporating a smartphone for signal reading, eliminating the need for specialised equipment and significantly reducing the detection cost. This cost-effective approach carries the potential to expedite on-site and naked-eye I2 detection, opening up new possibilities for research and application.

Manganese deficiency alters photosynthetic electron transport in Marchantia polymorpha

Manganese (Mn) is considered as an essential element for plant growth. Mn starvation has been shown to affect photosystem II, the site of the Mn4CaO5 cluster responsible for water oxidation. Less is known on the effect of Mn starvation on photosystem I. Here we studied the effects of Mn deficiency in vivo on redox changes of P700 and plastocyanin (Pc) in the liverwort Marchantia polymorpha using the KLAS-NIR spectrophotometer. Far-red illumination is used to excite preferentially photosystem I, thus facilitating cyclic electron transport. Under Mn starvation, we observed slower oxidation of P700 and a decrease in the Pc signal relative to P700. The lower Pc content under Mn deficiency was confirmed by western blots. Re-reduction kinetics of P700+ and Pc+ were faster in Mn deficient thalli than in the control. The above findings show that the kinetics studied under Mn deficiency not only depend on the number of available reductants but also on how quickly electrons are transferred from stromal donors via the intersystem chain to Pc+ and P700+. We suggest that under Mn deficiency a structural reorganization of the thylakoid membrane takes place favoring the formation of supercomplexes between ferredoxin, cytochrome b6f complex, Pc and photosystem I, and thus an enhanced cyclic electron transport.

Multifaceted Proteome Analysis at Solubility, Redox, and Expression Dimensions for Target Identification.

Multifaceted interrogation of the proteome deepens the system-wide understanding of biological systems; however, mapping the redox changes in the proteome has so far been significantly more challenging than expression and solubility/stability analyses. Here, the first high-throughput redox proteomics approach integrated with expression analysis (REX) is devised and combined with the Proteome Integral Solubility Alteration (PISA) assay. The whole PISA-REX experiment with up to four biological replicates can be multiplexed into a single tandem mass tag TMTpro set. For benchmarking this compact tool, HCT116 cells treated with auranofin are analyzed, showing great improvement compared with previous studies. PISA-REX is then applied to study proteome remodeling upon stimulation of human monocytes by interferon α (IFN-α). Applying this tool to study the proteome changes in plasmacytoid dendritic cells (pDCs) isolated from wild-type versus Ncf1-mutant mice treated with interferon α, shows that NCF1 deficiency enhances the STAT1 pathway and modulates the expression, solubility, and redox state of interferon-induced proteins. Providing comprehensive multifaceted information on the proteome, the compact PISA-REX has the potential to become an industry standard in proteomics and to open new windows into the biology of health and disease.

In vivo redox imaging of plasma-induced skin-inflammation in mice

Cold atmospheric plasma (CAP) generates reactive oxygen species (ROS) which induce biological effects on living cells. CAP has potential applications in medicine, but its highly reactive nature can lead to adverse skin complications. A noninvasive technique to examine redox changes in skin is needed for monitoring the treatment process. This study was conducted to develop a skin-inflammation model triggered by CAP-derived ROS and to monitor its progression noninvasively by in vivo dynamic nuclear polarization-MRI (DNP-MRI). The model was successfully developed by exposing the skin to both direct and remote modes of CAP. In vivo DNP-MRI imaging revealed faster reduction rates of TEMPOL in plasma-irradiated skin-inflammation areas, particularly in the remote mode plasma-irradiated skin. MRI revealed high-intensity areas in both the superficial and deep layers of the plasma-irradiated skin. The study highlights the potential importance of DNP-MRI in imaging skin-inflammation models and could improve the use of CAP in medical treatments.

Abstract Tu138: Tandem Mass Tagging (TMT)-based Identification of Proteome Signatures for Ischemia-Reperfusion Injury in Swine

Background: The composition of proteins in blood plasma mirrors the physical changes occurring in the course of disease pathogenesis. Currently available clinical markers are insufficient to predict the actual damage and the redox changes in response to ischemia. Hence, we identified novel redox markers for ischemia/reperfusion (I/R) in swine using TMT-proteomics. Methodology: We employed TMT-10plex isobaric labeling-based quantitative proteomics to track the plasma proteome in Sus Scorfa pigs subjected to surgical I/R at different time points. Plasma samples were collected before ischemia, at 1-hr after ischemia (baseline), and 4-hr, 24-hrs, and 7 days following reperfusion. Results: An average of 4853 spectra and a total of 457 proteins were identified, ensuring a 1% false discovery rate for peptides and proteins with at least two distinct peptides. Pre-ischemia plasma samples served as the control group in all the analyses. TMT analysis revealed temporal changes in the plasma proteome with a prominent shift at 4 hours after I/R insult. To investigate the significantly changed proteins (>1.5 fold), a temporal analysis was carried out. Notably, endopin-1, a serpin protein family member, and fibronectin B were detectable in the plasma following 4 hours of ischemia-reperfusion, indicating the release of these proteins in the circulation during the ischemia-reperfusion. A positive correlation was observed between the redox proteins (i.e., catalase and glutathione peroxidase) with the serpin proteins in the plasma. Biochemical analysis of circulating glutathione, a small-molecular antioxidant, revealed a reductive redox after 60 minutes of Ischemia (hypoxic condition) but this was shifted to an oxidative milieu at 4hrs following reperfusion (hyperoxia) in the adult pigs subjected to I/R insult. Interestingly, we noticed a significant increase in GSH levels and a decrease in catalase levels at 24 hours following I/R, suggesting a compensatory biochemical response in association with repair after I/R insult/injury in the heart. These results correlated with the increased circulating LDH levels indicating the rate of tissue damage following I/R. Conclusion: The present study reveals the presence of a previously unexplored Serpin protein member, endopin-1, during I/R. Understanding the kinetics of endopin-1 expression along with the shift in redox state can help unravel its role in the progression and resolution phases of I/R injury.

Redox changes in the Iapetus Ocean during the Late Ordovician extinction crises

The cause of the Late Ordovician mass extinction (LOME) is widely debated, with glaciation, volcanism and oceanic redox fluctuations being proposed as possible drivers. Here, we apply a multi-proxy approach to deep-water Iapetus Ocean samples from Dob's Linn, Scotland, to determine oceanic redox conditions and changes in chemical weathering intensity. We document major redox fluctuations between anoxic ferruginous and oxic conditions during the first, end-Katian extinction pulse, whereas the end-Hirnantian extinction phase witnessed more persistent anoxia. These two episodes were separated by oxic conditions and a major, short-lived decline in chemical weathering during the Hirnantian glaciation, suggesting that although global cooling may have placed stress on certain biota, it was unlikely to be the cause of the extinction crisis. Late Hirnantian anoxia persisted into the Silurian, with widespread euxinia resulting in global drawdown of redox-sensitive trace metals. Recent studies have identified a mid-Katian biotic crisis and recovery prior to the LOME, although the precise stratigraphic position is not yet defined. The mid-Katian record at Dob's Linn shows a major redox change, with dysoxic to anoxic ferruginous deep ocean waters giving way to well-oxygenated conditions at this time. However, links between the mid-Katian biotic crisis and these redox changes remain unclear.

The impact of chemical pollution across major life transitions: a meta-analysis on oxidative stress in amphibians.

Among human actions threatening biodiversity, the release of anthropogenic chemical pollutants which have become ubiquitous in the environment, is a major concern. Chemical pollution can induce damage to macromolecules by causing the overproduction of reactive oxygen species, affecting the redox balance of animals. In species undergoing metamorphosis (i.e. the vast majority of the extant animal species), antioxidant responses to chemical pollution may differ between pre- and post-metamorphic stages. Here, we meta-analysed (N = 104 studies, k = 2283 estimates) the impact of chemical pollution on redox balance across the three major amphibian life stages (embryo, tadpole, adult). Before metamorphosis, embryos did not experience any redox change while tadpoles activate their antioxidant pathways and do not show increased oxidative damage from pollutants. Tadpoles may have evolved stronger defences against pollutants to reach post-metamorphic life stages. In contrast, post-metamorphic individuals show only weak antioxidant responses and marked oxidative damage in lipids. The type of pollutant (i.e. organic versus inorganic) has contrasting effects across amphibian life stages. Our findings show a divergent evolution of the redox balance in response to pollutants across life transitions of metamorphosing amphibians, most probably a consequence of differences in the ecological and developmental processes of each life stage.

Dolostone-barite-phosphorite sequence in the basal Doushantuo Formation: Origin and implications for post-Marinoan ocean chemistry and phosphogenesis

Barite (BaSO4) represents a major component of many post-Marinoan cap dolostones worldwide, recording important information on climate upheavals during the terminal Neoproterozoic. However, its origins and relations with other lithofacies remain to be explored. Here we report new occurrences of barite in the basal Ediacaran Doushantuo Formation at a major phosphate mine in Weng'an, South China, and present results of detailed petrographic and geochemical investigations on the barites and related phases. At the outcrop scale, barite is mainly present as a 1–2 cm-thick layer at the contact of the cap dolostones and overlying phosphorites. Detailed petrographic observations reveal a lithofacies transition from dolostone through a mixture of barite, dolomite and apatite to barite and finally to granular phosphorite. The barites can be categorized into three generations in stratigraphic order, which are present as loose, randomly-oriented blades (B1), dense aggregates (B2), and radially aligned crystal fans (B3), respectively. B1 is dispersed in a matrix of apatite and dolomite, which has an average δ13Ccarb of −0.61‰. This, along with the common presence of organic matter (OM) in this barite, point to a possible source of Ba from organic degradation. B3 forms a centimeter-scale layer of barite fans that laterally extends over the entire mining pit, whereas B2 is locally distributed between B1 and B3, and occurs as relatively unoriented aggregates. δ34S values of B3 show a narrow range between +25.9‰ and +30.9‰, which is similar to that of contemporaneous seawater and indicate a seawater source of sulfate in barite. Based on the present investigation and a compilation of published data, we propose that B1 is diagenetic barite with a main source of Ba from degradation of organic matter and possibly also from dissolution of previous pelagic barite, whereas B2 and B3 represent seafloor precipitates that resulted from interactions between deep, anoxic Ba-rich waters and oxic, sulfate-rich surface waters during the post-glacial transgression. This episode of barite precipitation was immediately followed by massive accumulations of phosphorites in Weng'an and many areas of South China. The consecutive deposition of cap dolostone, barite and phosphorite signifies the transition from an alkalinity-rich, stagnant anoxic ocean to a dynamic marine regime featuring oxygenated surface waters and upwelling currents. These pH and redox changes likely facilitated the cycling and enrichment of phosphate in the shallow waters that was necessitated by the unprecedented accumulation of Ediacaran phosphorites in South China.