Restricted Oxygen Research Articles

Determination of beneficial effects of cuminaldehyde on hyperglycemiaassociated kidney malfunctions.

Type 1 diabetes mellitus is defined by the autoimmune destruction of pancreatic β cells, with diabetic nephropathy being a significant consequence. Recently, cuminaldehyde has been shown protective ability against various pathophysiology. However, its nephroprotective and anti-diabetic potential has not yet been fully understood. We, therefore, conducted the present study to evaluate the anti-hyperglycemic potential of cuminaldehyde in NRK52E cells without (control) or with high glucose medium to emulate hyperglycemic conditions. Cuminaldehyde pre-treatment at an optimal concentration of 175μM prior to high glucose addition restricted excessive reactive oxygen species (ROS) production and maintained cellular morphology to almost normal. The inhibitor study using N-acetyl-l-cysteine confirmed that blocking of ROS assists NRK52E cells in evading apoptosis. In addition, hyperglycemia was induced in 6-week-old Swiss albino mice in this investigation through the intraperitoneal injection of streptozotocin (150mgkg-1 body weight). Hyperglycemia increased the kidney-to-body weight ratio, lowered serum insulin levels, and led to significant renal tissue damage compared to control mice. Moreover, hyperglycemia disturbs cellular redox equilibrium by decreasing antioxidant enzyme functions and promoting inflammatory cytokines in kidney tissue. Administering cuminaldehyde at a dosage of 10mgkg-1 body weight for 5weeks daily after the onset of diabetes effectively ameliorated the aforementioned anomalies and reversed kidney damage by regulating inflammation-induced cell death. Overall, the research demonstrated that cuminaldehyde has hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties. We believe that after conducting extensive research, this unique molecule can be used in clinical trials against diabetic nephropathy in future.

Carbon fibres: Effect of various thermo-oxidative environments on structural and performance damage, both alone and in composites

This study examines the effects of heat and fire on the physical, mechanical and electrical properties of carbon fibre and those in carbon fibre reinforced composites (CFRCs). Carbon fibres were exposed to controlled heating (thermogravimetric analysis (TGA) and a tube furnace) in inert and air (oxygenated) environments and simulated fire (cone calorimetry at 35–75 kW m−2 and jet fire (propane burner) of 116 kW m−2) atmospheres. In inert atmospheres there was a minimal effect on the properties of carbon fibres, but in an oxygenated environment, significant oxidation began at temperatures ≥550 °C, resulting in a reduction in fibre diameter, which reduced further with increasing temperature and exposure duration. Tensile strength and electrical conductivity of carbon fibre decreased with reduction in fibre diameter. CFRCs exposed to 75 kW m−2 in a cone calorimeter and direct flame in a propane burner (116 kW m−2) showed varying degrees of oxidation in CFRC plies, with surface ply fibres experiencing more oxidation and consequent reductions in fibre diameter and tensile properties compared to fibres in underlying plies, where oxidation was limited due to restricted oxygen availability. Fibres exposed to the propane burner exhibited notable damage, including pitting and internal oxidation. Despite this, the overall electrical properties of residual carbon fibres did not significantly decrease, indicating that they still pose an electrical hazard if exposed during a high heat or fire event.

Physiological Metabolic Analysis of VB12 Accumulation in Ensifer adhaerens Casida A Enhanced by Oxygen Limitation.

Cobalamin (VB12) is in enormous demand across the fields of medicine, food, and feed additives. However, the oxygen supply plays a critical role in VB12 biosynthesis by Ensifer adhaerens Casida A and has been identified as a bottleneck for economical substrate consumption. This study elucidates the relationship between oxygen limitation and VB12 accumulation with transcriptomic and metabolomic analyses. Under oxygen limitation, E. adhaerens enhances oxygen transport and storage by increasing expression of flavin hemoglobin (Hmp), which was up-regulated 6-fold at 24h of oxygen restriction compared to the oxygen restriction of 4h (p<0.01). Because of the cofactor of Hmp is heme, the demand for heme increases, leading to the upregulation of genes in the heme biosynthesis pathway. Similarly, genes involved in biosynthesis of its precursor, 5-ALA, were upregulated as well. 5-ALA is also a direct precursor of VB12, further leading to the upregulation of genes in the VB12 biosynthesis pathway. This process initiates biosynthesis and accumulation of VB12. As VB12 and heme biosynthesis progresses, genes associated with the biosynthesis and transportation pathways of compounds related to their biosynthesis were likewise upregulated, including genes involved in S-adenosyl methionine (SAM) biosynthesis, and the transport of Fe2+ and Co2+. Additionally, amino acids and organic acids associated with biosynthesis were also extensively consumed, such as methionine, which is used for synthesizing SAM, decreased by 310% after 24 h of oxygen limitation compared to 20% dissolved oxygen (p<0.05). At the same time, genes related to growth-associated metabolic pathways, such as pentose phosphate pathway (PPP), were significantly downregulated. Therefore, the potential mechanism by which E. adhaerens accumulates VB12 under oxygen-limited conditions by enhancing Hmp expression, which facilitates the porphyrin metabolic pathway and promotes VB12 biosynthesis. This research provides valuable insights for increasing VB12 production through metabolic engineering and process optimization.

The Long-Term Impact of Cardiac Rehabilitation on Cognitive Function in Older Patients With Myocardial Infarction: A Systematic Review.

Myocardial Infarction (MI) isan obstruction in the coronary arteries, resulting in restricted blood flow and oxygen supply to the heart, leading to damage to the heart's tissues. Beyond the cardiovascular system, the impact of MI extends to potentially affecting cognitive abilities, especially in elderly populations. To optimize patient recovery and long-term outcomes, timely cardiac interventions and subsequent rehabilitation programs are essential. This systematic review aims to assess the potential benefits of cardiac rehabilitation (CR) in enhancing cognitive function among elderly individuals who have experienced an MI. The review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and utilizes PubMed, PubMed Central, Cochrane, Google Scholar, and ScienceDirect databases. Studies included in the review encompass meta-analyses, controlled trials, systematic/narrative reviews, randomized/nonrandomized trials, observational studies, and research articles published within the past five years. Only accessible, full-text English-language studies meeting the inclusion criteria are selected, while books, documents over five years old, animal studies, and individuals under 65 are excluded. Following a predefined template, the initial search identifies 4,915 studies. From this pool, 27 free full-text articles are then selected for quality appraisal based on relevance. After performing a quality assessment on each survey, 12 high-quality studies are included in this systematic review. The research studies demonstrate notable cognitive improvements among elderly patients who have experienced an MI and participated in CR programs. Additional clinical trial studies are recommended to substantiate these findings further and advance our understanding.

Glucose-oxygen deprivation constrains HMGCR function and Rac1 prenylation and activates the NLRP3 inflammasome in human monocytes.

Hypoxia and low glucose abundance often occur simultaneously at sites of inflammation. In monocytes and macrophages, glucose-oxygen deprivation stimulates the assembly of the NLRP3 inflammasome to generate the proinflammatory cytokine IL-1β. We found that concomitant glucose deprivation and hypoxia activated the NLRP3 inflammasome by constraining the function of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate kinase pathway. HMGCR is involved in the synthesis of geranylgeranyl pyrophosphate (GGPP), which is required for the prenylation and lipid membrane integration of proteins. Under glucose-oxygen deprivation, GGPP synthesis was decreased, leading to reduced prenylation of the small GTPase Rac1, increased binding of nonprenylated Rac1 to the scaffolding protein IQGAP1, and enhanced activation of the NLRP3 inflammasome. In response to restricted oxygen and glucose supply, patient monocytes with a compromised mevalonate pathway due to mevalonate kinase deficiency or Muckle-Wells syndrome released more IL-1β than did control monocytes. Thus, reduced GGPP synthesis due to inhibition of HMGCR under glucose-oxygen deprivation results in proinflammatory innate responses, which are normally kept in check by the prenylation of Rac1. We suggest that this mechanism is also active in inflammatory autoimmune conditions.

Evolution of heavy components in bio-oil during oxidative pyrolysis of cellulose, hemicellulose, and lignin

Biomass oxidative pyrolysis introduces restricted oxygen into the reaction zone, realizing autothermal pyrolysis to address the heat supply challenges inherent in large-scale applications. However, heavy components (＞200 Da) in bio-oil are critical precursors that lead to coke formation upon heating, which hinders the utilization of bio-oil. In this study, the conventional and oxidative pyrolysis experiments of cellulose, hemicellulose, and lignin in a fix-bed reactor were conducted at temperatures ranging from 300 °C to 800 °C, aiming to investigate the evolution of heavy components in bio-oil during biomass oxidative pyrolysis. The results showed that the addition of oxygen promoted the generation of bio-oil. Compared to conventional pyrolysis, the addition of oxygen mostly increased the yields of cellulose-oil, hemicellulose-oil, and lignin-oil by 28.21 %, 10.94 %, and 16.84 %, respectively. Further comprehensive analysis revealed that oxygen promoted the depolymerization of three components at a lower temperature range (＜ 500 °C). With increasing temperatures, oxygen enhanced the polymerization of volatiles from cellulose and lignin, where oxygen, acting as a binder, promoted the generation of phenolic compounds of heavy components in lignin-oil. Conversely, as the temperature increased, oxygen enhanced the oxidative decomposition of volatiles from hemicellulose, inhibiting the generation of heavy components in hemicellulose-oil. To sum up, this study presented a global evolution route of heavy components in bio-oil during oxidative pyrolysis of three components.

Thermodynamic characteristics and mechanism of low-rank coal oxidation in oxygen-poor environment

Aiming at the restricted oxygen environment of coal mine, this paper focus on the whole process from physical adsorption to chemical reaction between coal and oxygen, and quantum chemical calculations investigate the potentiating or inhibiting effects of different active groups on the amount of oxygen adsorbed and thermally released from the main coal structure, and experimentally investigate the effect of oxygen concentration (OC) on the transformation relationship between active functional groups and active sites. The results showed the coal side-chain structure has an effect on the heat release characteristics of the aromatic ring in the process of oxygen adsorption, and the heat of adsorption of the aromatic ring with alkyl and aldehyde side-chains reaches 422.706 kJ/mol. The relationship between carbon oxide release and temperature at different OC all conformed to the exponential function model, and the apparent activation energy was positively correlated with the OC. The increase of OC narrows the gap between the production and consumption rates of active sites, which is helpful for the further understanding of the coal spontaneous combustion (CSC).

Effects of remote ischemic preconditioning on early markers of intestinal injury in experimental hemorrhage in rats

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO2), microvascular flow index (MFI) and plasmatic d-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock.

Sweet dreams could be made of this: carbohydrate-responsive element-binding protein (ChREBP) as a target for hepatocellular carcinoma therapy.

Rewiring of cellular metabolism is now fully recognized as a hallmark of cancer. Tumor cells reprogram metabolic pathways to meet the energetic and macromolecular demands to support unrestricted growth and survival under unfavorable conditions. It is becoming apparent that these adaptations underpin most of the traits that define a cancer cell's identity, including the ability to avoid immune surveillance, endure nutrient and oxygen restrictions, detach and migrate from their natural histological niche, and avert human-made aggressions (i.e., therapy). In a recent study, Benichou and collaborators identify carbohydrate-responsive element-binding protein (ChREBP), a master regulator of physiological glucose metabolism, as an oncogene in hepatocellular carcinoma (HCC) development. Upregulation of ChREBP expression results in a self-stimulatory loop interconnecting PI3K/AKT signaling and glucose metabolism to feed fatty acid and nucleotide synthesis supporting tumorigenesis. Importantly, pharmacological inhibition of ChREBP activity quells in vivo HCC tumor growth without causing systemic toxicity. This study identifies novel oncometabolic pathways and open up new avenues to improve the treatment of a deadly tumor.

Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Plain Language SummaryIn this study, we tested a new treatment for a disease in babies called hypoxic-ischemic encephalopathy (HIE). HIE is caused by restricted oxygen and blood flow around the time of birth, and most damage is caused when blood flow is restored. One reason for this is excess inflammation, which happens because a large amount of specific proteins and chemicals are released. Some inflammation is protective, but excessive inflammation injures healthy tissue, and in HIE this contributes to lifelong physical and mental disabilities, even death. The only treatment for HIE is cooling therapy, but even with this treatment many infants still do not survive or live with permanent disability. We mimicked the disease in rats and then gave them a drug that prevents excess inflammation by binding and disabling specific proteins. We measured improvement by comparing physical and mental abilities and brain damage in the treated rats to untreated and normal rats. Overall, the drug improved many but not all skills and parts of the brain harmed by the disease. More testing needs to be done to determine the optimal dose and if there is additional benefit when the drug is combined with cooling therapy. In closing, our results show this treatment warrants further development and could help infants grow up with less hardship and lead better, healthier lives.

Eco-friendly multifunctional coating for polyester-cotton blended fabrics with superior flame retardancy and antibacterial properties

Since the fire hazards of polyester-cotton blended (PTCO) fabrics and the hidden dangers of bacterial infection concerns caused by the contained cotton fiber, the design of flame retardant and antibacterial PTCO fabrics has received considerable attention. In this work, flame-retardant PTCO fabrics with satisfactory antibacterial properties were fabricated via a convenient and eco-friendly impregnation treatment involving guanidine phosphate (GP) and polyethylenimine (PEI). The prepared PTCO fabrics demonstrated excellent flame retardancy with a high limiting oxygen index value of 30.5 % and self-extinguishing capability, the damaged length was only 34 mm in the vertical flammability test. Furthermore, the peak heat release rate and the total heat release of coated PTCO fabrics were reduced significantly by 49 % and 38 %, respectively, indicating a substantial enhancement in fire safety. According to the analysis of the char residues and volatiles, GP presented great catalytic carbonization property, and PEI assisted the formation of the dense and stable carbon layer. The stable carbon layer effectively restricted mass and oxygen transfer between the PTCO fabrics and the environment. In addition, the introduction of PEI also produced more nonflammable gases to enhance the flame retardancy of the PTCO fabrics. Importantly, the GP/PEI coating barely deteriorate the physical and mechanical properties of the PTCO fabrics. The antibacterial rate of the GP/PEI-coated PTCO fabrics against Escherichia coli and Staphylococcus aureus was 99.99 %, similar to that of GP-coated fabrics, indicating the efficacy antibacterial properties of GP, and the addition of PEI did not compromise the antibacterial properties of GP. This work offers an efficient and simple approach to producing multifunctional PTCO fabrics with excellent flame retardancy and antibacterial properties, which are hopeful to expand the promising application of PTCO fabrics.

Oxygen targets following immediate percutaneous coronary intervention in comatose survivors of out-of-hospital cardiac arrest - a BOX sub-study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Novo Nordisk Foundation The Lundbeck Foundation. Background Treatment with supplemental oxygen in patients with acute myocardial infarction (AMI) has previously been associated with poorer outcomes. However, in patients with AMI resuscitated from out-of-hospital cardiac arrest (OHCA) and undergoing immediate revascularization, evidence regarding specific oxygen targets is sparse. Purpose To assess the impact of a restrictive versus a liberal oxygen target on infarct size in OHCA patients undergoing immediate percutaneous coronary intervention (PCI). Methods The current study is a sub-study of the BOX trial, a randomized trial with a 2-by-2 factorial design, in which comatose OHCA patients with a presumed cardiac cause of arrest were randomly assigned to either a restrictive oxygen target (partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa) or a liberal oxygen target (Pao2 of 13 to 14 kPa). In this sub-study we included patients who underwent immediate revascularization with PCI. The primary outcome was myocardial infarct size as assessed by the cardiac enzyme troponin-T (TnT). TnT was measured repeatedly during the first 72 hours and analyzed with a repeated measures variance component model with baseline adjustment. Secondary outcome was one-year all-cause mortality assessed by Kaplan-Meier and Cox proportional hazards analyses. Results A total of 329 patients underwent immediate PCI, whereof 172 patients were randomized to the restrictive oxygen target and 157 to the liberal oxygen target. The oxygen intervention was successful with a significantly higher PaO2 in the liberal oxygen target group during the first 72 hours (p&amp;lt;0.0001). Baseline characteristics and findings on coronary angiography (CAG) were similar in the two oxygen target groups. Thus, median age was 63 (interquartile range (IQR) 55–71), 81% were male, and estimated left ventricular ejection fraction on arrival to hospital was 35% (IQR 25–45%). Further, 74% of the patients had an initial postresuscitation electrocardiogram with ST-segment elevations, and the left anterior descending artery was deemed as culprit lesion in 49% of the patients. There was no difference in peak TnT between the restrictive and liberal oxygen target group (median 2540 (IQR 925–6420) versus 3410 (792–8630), ng/l, p=0.23), nor did TnT differ between the groups during the first 72 hours after admission (Figure 1, p=1.00). Within one year from admission, 120 patients (36.5%) had died. There was no difference in mortality between the restrictive (34%) and liberal (39%) oxygen target group (hazard ratio, 0.80; 95% CI, 0.56-1.14; p=0.21) (Figure 2). Conclusion Targeting a restrictive versus a liberal oxygen level in comatose survivors of OHCA who underwent immediate revascularization did not affect infarct size nor did it result in a significant difference in one-year mortality rate.Figure 1:Troponin-T levelsFigure 2:Kaplan-Meier curves

Oxygen delivery and consumption in comatose out-of-hospital cardiac arrest patients are affected by blood pressure targets

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grosserer L. F. Foghts Fond Background Hemodynamic instability is common after resuscitated out-of-hospital cardiac arrest (OHCA). Preventing inadequate oxygen delivery (DO2) to the cells and thus not meeting oxygen demand is crucial to prevent further organ dysfunction. Additionally, oxygen uptake in the cells may be impaired. Oxygen consumption (VO2; the amount of oxygen consumed by the body per minute) could thus also be affected in OHCA. Purpose This study aimed to describe the effect of different mean arterial blood pressure (MAP) and partial arterial oxygen pressure (PaO2) targets on DO2 and VO2. Methods This post-hoc study is based on the BOX trial, a 2x2 factorial design that randomized OHCA patients to a MAP of either 63 mmHg (MAP63) or 77 mmHg (MAP77) and a partial pressure of arterial oxygen of 9 to 10 kPa or a liberal oxygen target of a PaO2 of 13 to 14 kPa at two cardiac centers in Denmark. Pulmonary artery catheters were placed to evaluate cardiac output and collect mixed venous blood samples at prespecified time points. Oxygen blood contents were calculated for arterial (CaO2) and mixed venous blood (CvO2) as Hgb (mg/dl) x 10 x 1.39 x Saturation O2 (proportion) + 0.0225 x PaO2. DO2 = CO x CaO2, and VO2 = CO x (CaO2-CvO2). Results This study included 715 patients (90% of the total cohort with a pulmonary catheter) for analysis. A restrictive or liberal oxygen supplement did not affect DO2 or VO2 during the initial 48 hours. The MAP77 group exhibited on average 11% higher DO2 (95%CI: 6%-15%) and on average a 6% higher VO2 in the first 48 hours (95%CI: 3%-10%) compared to the MAP63 group (see Figure 1). Conclusion Targeting a PaO2 of either 9 to 10 kPa or 13 to 15 kPa resulted in no significant changes in the provision of oxygen to the cells, nor did it increase the consumption of oxygen. In contrast, targeting a MAP of 77 mmHg resulted in an increase in both the provision of oxygen and consumption of oxygen compared to a MAP target of 63 mmHg.Figure 1

Influence of aeration modes and DO on simultaneous nitrification and denitrification in treatment of hypersaline high-strength nitrogen wastewater using sequencing batch biofilm reactor (SBBR)

Sequencing batch biofilm reactor (SBBR) has the potential to treat hypersaline high-strength nitrogen wastewater by simultaneous nitrification-denitrification (SND). Dissolved oxygen (DO) and aeration modes are major factors affecting pollutant removal. Low DO (0.35–3.5 mg/L) and alternative anoxic/aerobic (A/O) mode are commonly used for municipal wastewater treatment, however, the appropriate DO concentration and operation mode are still unknown under hypersaline environment because of the restricted oxygen transfer in denser extracellular polymeric substances (EPS) barrier and the decreased carbon source consumption during the anoxic phase. Herein, two SBBRs (R1, fully aerobic mode; R2, A/O mode) were used for the treatment of hypersaline high-strength nitrogen wastewater (200 mg/L NH4+-N, COD/N of 3 and 3% salinity). The results showed that the relatively low DO (2 mg/L) could not realize effective nitrification, while high DO (4.5 mg/L) evidently increased nitrification efficiency by enhancing oxygen transfer in denser biofilm that was stimulated by high salinity. A stable SND was reached 16 days faster with a ∼10% increase of TN removal under A/O mode. Mechanism analysis found that denser biofilm with coccus and bacillus were present in A/O mode instead of filamentous microorganisms, with the secretion of more EPS. Corynebacterium and Halomonas were the dominant genera in both SBBRs, and HN-AD process might assist partial nitrification-denitrification (PND) for highly efficient TN removal in biofilm systems. By using the appropriate operation mode and parameters, the average NH4+-N and TN removal efficiency could respectively reach 100% and 70.8% under the NLR of 0.2 kg N·m−3·d−1 (COD/N of 3), which was the highest among the published works using SND-based SBBRs in treatment of saline high-strength ammonia nitrogen (low COD/N) wastewater. This study provided new insights in biofilm under hypersaline stress and provided a solution for the treatment of hypersaline high-strength nitrogen (low COD/N) water.

Effect of Fe doped Co–Ni protective coatings on the oxidation behavior and electrical properties of SOFC alloy interconnect materials

In order to enhance the oxidation resistance and electrical properties of interconnects for solid oxide fuel cells (SOFCs), three Co–Ni alloy coatings with varying contents of Fe doping were prepared onto SUS 430 substrate using electroplating method and oxidized in air at 800 °C for 1000 h. The experimental results demonstrated that the alloy coating significantly enhanced both the oxidation resistance and electrical properties of the interconnect substrate. The multi-layer oxidation structure blocked Cr from diffusing outward. Notably, the (Co,Fe)3O4/(Ni,Co)O in the oxidized layer of 5% Fe doped Co–Ni coated steel completely transformed into (Fe,Co,Ni)3O4 spinel layer after long term oxidation, which had the lowest activation energy and the strongest ability of restricting oxygen diffusion inward. Thus, the 5% Fe doped Co–Ni coated steel showed superior oxidation resistance (kp = 8.76 × 10−14 g2 cm−4 s−1) and excellent electrical properties (ASR = 13.19 mΩ cm2) following oxidation for 1000 h.

O132: Impaired oxygen unloading from stored blood results in diffusion-limited oxygen release at tissues: evidence from twinned-circuit human kidney perfusion

Abstract Background The storage lesion is a multifactorial degradation effect seen in units of banked blood, and results in an increase in the time-constant of oxygen-unloading from red cells (tau). We have previously shown the relevance of this effect in observational data from a recent clinical trial of prolonged normothermic kidney perfusion as a preservation technique ahead of transplantation. We sought direct confirmatory evidence for diffusion-limited oxygen release by stored red cells (RBCs) during normothermic kidney perfusion in a precisely controlled experimental setting. Methods A novel twinned-circuit kidney perfusion system using common, recirculated dialysis was developed, achieving physical separation of RBCs of two conditions whilst allowing non-cellular components of the perfusate to equilibrate throughout. Using human kidneys unsuitable for transplantation, perfusion was alternated between stored and rejuvenated RBCs (treated with PIPA solution) originating from the same donation, to manipulate oxygen-unloading whilst holding all non-RBC parameters constant, without interrupting blood flow. Results Tau improved with PIPA treatment (1.6 to 1.1s). Rejuvenated oxygen-unloading kinetics reversibly and significantly improved the kidney’s oxygen diffusion capacity and increased cortical oxygen tension by 60%. This supported observations from our clinical trial, where increased tau was strongly associated with restricted renal oxygen consumption. Conclusions We have confirmed that oxygen delivery to tissues can become diffusion-limited during normothermic perfusion with stored blood. This effect is reversible by treatment with PIPA solution. This has important implications for ex-vivo normothermic organ perfusion, and potentially for other scenarios such as major hemorrhage, elective surgery with high blood product utilisation, and paediatric transfusion.

Engineering and Characterization of 3-Aminotyrosine-Derived Red Fluorescent Variants of Circularly Permutated Green Fluorescent Protein.

Introducing 3-aminotyrosine (aY), a noncanonical amino acid (ncAA), into green fluorescent protein (GFP)-like chromophores shows promise for achieving red-shifted fluorescence. However, inconsistent results, including undesired green fluorescent species, hinder the effectiveness of this approach. In this study, we optimized expression conditions for an aY-derived cpGFP (aY-cpGFP). Key factors like rich culture media and oxygen restriction pre- and post-induction enabled high-yield, high-purity production of the red-shifted protein. We also engineered two variants of aY-cpGFP with enhanced brightness by mutating a few amino acid residues surrounding the chromophore. We further investigated the sensitivity of the aY-derived protein to metal ions, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Incorporating aY into cpGFP had minimal impact on metal ion reactivity but increased the response to RNS. Expanding on these findings, we examined aY-cpGFP expression in mammalian cells and found that reductants in the culture media significantly increased the red-emitting product. Our study indicates that optimizing expression conditions to promote a reduced cellular state proved effective in producing the desired red-emitting product in both E. coli and mammalian cells, while targeted mutagenesis-based protein engineering can further enhance brightness and increase method robustness.

Reconfiguring oxygenation at ∼1.4 Ga: New constraints as informed by the ancient oceanic sulfur cycle

The extent of atmospheric and oceanic oxygenation during the Mesoproterozoic remains an area of active debate. Here, we report major and trace elements, organic sulfur (OS) speciation, sulfur isotopes in multiple phases [pyrite (py), OS, and carbonate-associated sulfate (CAS)], and a numerical model of sulfate concentrations from one of the Mesoproterozoic's best-preserved geochemical archives, the Xiamaling Formation (ca. 1.4 Ga) in the Yanliao Basin. These data reveal a previously unrecognized ocean-atmosphere oxygenation process. Starting with Unit 3, intense sulfurization increased organic carbon burial and thus oxygen release, resulting in a deep-water oxidation event within the Yanliao Basin that could be regarded as a transient restricted oxygen oasis based on low pyrite content, elevated kerogen S:C ratios, higher δ34Spy than δ34SOS (Δδ34SOS-py < 0), and a low calculated sulfate concentration of ∼0.07–0.14 mM. During Unit 2, the basin was reconnected to the open ocean with the deposition of organic-rich shale across northern China and northern Australia, accompanied by a shift in Δδ34SOS-py to 5.0‰ and a calculated seawater sulfate concentration of ∼0.1–1.14 mM. Such large-scale burial of organic matter released oxygen into the atmosphere, accompanied by significant sulfate delivery to the basin and euxinic conditions characterized by Mo concentrations and 34S-depleted pyrite at the topmost of Unit 2. A subsequent globally synchronized atmospheric and deep ocean oxygenation event may have occurred during Unit 1. This event was recorded by a progressive increase in Δδ34SOS-py (up to +9.6‰), increased oxidized OS species, and positive Ce anomalies (attributed to the reductive dissolution of the Ce-enriched Mn oxides), all of which were caused by increased sulfate concentrations (calculated to be ∼1.15–2.31 mM) and a spatial descent of the redox interface. The combination of these lines of evidence illustrates the sensitivity of the oceanic sulfur cycle to the ocean-atmosphere system and provides novel constraints on oxygenation at ∼1.4 Ga.

Oxygen Targets After Cardiac Arrest: A Meta-analysis of Randomized Controlled Trials.

Optimal oxygen saturation target in patients resuscitated after cardiac arrest is unknown. Previous randomized controlled trials (RCTs) comparing restrictive oxygen therapy with liberal therapy have shown conflicting results. We performed a meta-analysis of available RCTs to consolidate the contrasting findings regarding the oxygen targets after cardiac arrest. We searched electronic databases for RCTs comparing restrictive versus liberal oxygen targets in patients resuscitated after cardiac arrest. End points of interest were mortality, unfavorable neurological outcomes, and rearrests. Random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). Eight RCTs with 1641 patients (restrictive n = 833, liberal n = 808) were included in the analysis. The oxygen targets were defined by either saturation, partial pressure (PaO2), or supplementation rates. The mean age and male percentage were 63 years and 80%, respectively. There was no significant difference observed in the 2 groups for overall mortality (RR = 0.91, 95% CI = 0.75-1.10, P = 0.33), unfavorable neurological outcomes (RR = 0.93, 95% CI = 0.74-1.18, P = 0.56), and rearrests (RR = 0.67, 95% CI = 0.22-1.98, P = 0.47). Overall, this meta-analysis shows no significant difference in mortality, unfavorable neurological outcomes, and rearrests when using restrictive or liberal oxygen targets in patients after cardiac arrest. The limitations in the newer trials should be kept in mind while interpreting the overall results.

Root acclimations to soil flooding prime rice (Oryza sativa L.) for subsequent conditions of water deficit

Background and aimsThe root barrier to radial O2 loss is a trait induced during soil flooding restricting oxygen loss from the roots to the anoxic soil. It can also restrict radial water loss, potentially providing tolerance towards drought during conditions of water deficit. Several root traits (aerenchyma and xylem vessels area) respond in a similar way to soil flooding and low soil water potentials. Therefore, we hypothesised that root acclimations to soil flooding prime plants to withstand conditions of water deficit.MethodsWe raised plants in hydroponics mimicking contrasting soil water conditions (aerated controls for well-watered soils; stagnant, deoxygenated solutions for flooded soils, and aerated solutions with different PEG6000 concentrations to mimic conditions of water deficit). We used O2 microsensors and gravimetric measurements to characterize the formation of a barrier to radial O2 loss during conditions of water deficit, and measured key anatomical root traits using light microscopy.ResultsSeveral root traits were induced in stagnant conditions as well as in conditions of water deficit, including the barrier to radial O2 loss. The tightness of the barrier to water loss was similar in both stagnant and PEG6000 treatments. Moreover, plants growing in stagnant conditions tolerated a following severe condition of water deficit, whereas those growing in mimicked well-watered conditions did not.ConclusionsWe demonstrated that plants growing in stagnant conditions can withstand following severe conditions of water deficit. We propose that key root traits, such as the barrier to radial O2 loss, which are induced in stagnant conditions as well as mild conditions of water deficit, prime the plants for a following severe condition of water deficit.