Recent Advances in MR Imaging-based Quantification of Brain Oxygen Metabolism.

The metabolic rate of oxygen (MRO2) is fundamental to tissue metabolism. Determination of MRO2 demands knowledge of the arterio-venous difference in hemoglobin-bound oxygen concentration, typically expressed as oxygen extraction fraction (OEF), and blood flow rate (BFR). MRI is uniquely suited for measurement of both these quantities, yielding MRO2 in absolute physiologic units of µmol O2 min-1/100 g tissue. Two approaches are discussed, both relying on hemoglobin magnetism. Emphasis will be on cerebral oxygen metabolism expressed in terms of the cerebral MRO2 (CMRO2), but translation of the relevant technologies to other organs, including kidney and placenta will be touched upon as well. The first class of methods exploits the blood's bulk magnetic susceptibility, which can be derived from field maps. The second is based on measurement of blood water T2, which is modulated by diffusion and exchange in the local-induced fields within and surrounding erythrocytes. Some whole-organ methods achieve temporal resolution adequate to permit time-series studies of brain energetics, for instance, during sleep in the scanner with concurrent electroencephalogram (EEG) sleep stage monitoring. Conversely, trading temporal for spatial resolution has led to techniques for spatially resolved approaches based on quantitative blood oxygen level dependent (BOLD) or calibrated BOLD models, allowing regional assessment of vascular-metabolic parameters, both also exploiting deoxyhemoglobin paramagnetism like their whole-organ counterparts.

[Evaluation of the photodynamic effect on the state of microcirculation and oxygenation in periodontal tissues in the treatment of chronic generalized periodontitis]. / Otsenka fotodinamicheskogo vozdeistviya na sostoyanie mikrotsirkulyatsii i oksigenatsii v tkanyakh parodonta pri lechenii khronicheskogo generalizovannogo parodontita.

OBJECTIVE: Increasing the effectiveness of treatment of chronic generalized periodontitis using PDT based on clinical and functional substantiation of the effects of a photosensitizer. MATERIALS AND METHODS: A clinical and functional study and treatment of moderate chronic generalized periodontitis was carried out in 62 people (26 men and 36 women) aged from 35 to 55 years without a somatic model with an orthognathic occlusion diagnosed according to ICD-10 - K05.3. Of these, 2 groups were divided depending on the type of treatment: Group 1 (main) - patients with moderate chronic generalized periodontitis - 32 people. (17 men and 15 women, average age of the group - 43.2±2.2 years); Group 2 (control) - patients with moderate chronic generalized periodontitis - 30 people. (14 men and 16 women, average age of the group - 44.0±3.3 years). Complex treatment consisted of sanitation of the mouth, removal of dental plaque and curettage of periodontal pockets in group 1, followed by PDT with Revixan gel using a special wired aligner REVIXAN DENTAL LED (16 r). The clinical condition of the periodontium was assessed using the Greene Vermillion Hygienic Index (OHI-S), the Mühlleman Bleeding Index (SBI) modified by Cowell, and the periodontal index PI. To study the state of microcirculation in the gum tissue, the laser Doppler flowmetry (LDF) method was used using the LAKK-M device (NPP «Lazma¼, Russia). The state of microcirculation was assessed by the microcirculation index (M), which characterizes the level of tissue blood flow; parameter - «σ¼, which determines the fluctuation of the erythrocyte flow. According to Wavelet analysis of LDF-grams, the shunt index (SH) of blood flow was determined. In the «LDF + spectrometry¼ mode, oxygenation in periodontal tissues was studied using optical tissue oximetry (OTO), based on the results of which the perfusion saturation index (Sm) and the specific oxygen consumption index (U, %) were determined. RESULTS: According to LDF data, after PDT (group 1), normalization of clinical indices and the level of microcirculation in periodontal tissues was established, which was accompanied by an increase in the level of blood flow (M) and its activity (σ), which persisted after 3 and 6 months. after PDT. The perfusion saturation index (Sm) and specific oxygen consumption (U) increased more significantly after PDT, which persisted after 3 and 6 months. In the control group, the dynamics of indicators was less pronounced. CONCLUSION: The use of PDT with Revixan gel normalizes the clinical condition of the periodontium, indicators of microhemodynamics and oxygen metabolism.

H2S preconditioning induces long-lived perturbations in O2 metabolism.

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.

Vessel-specific quantification of cerebral venous oxygenation with velocity-encoding preparation and rapid acquisition.

PURPOSE: Non-invasive measurement of cerebral venous oxygenation (Yv) is of critical importance in brain diseases. The present work proposed a fast method to quantify regional Yv map for both large and small veins. METHODS: A new sequence was developed, referred to as TRU-VERA (T2 relaxation under velocity encoding and rapid acquisition, which isolates blood spins from static tissue with velocity-encoding preparation, modulates the T2 weighting of venous signal with T2-preparation and utilizes a bSSFP readout to achieve fast acquisition with high resolution. The sequence was first optimized to achieve best sensitivity for both large and small veins, and then validated with TRUST (T2 relaxation under spin tagging), TRUPC (T2 relaxation under phase contrast), and accelerated TRUPC MRI. Regional difference of Yv was evaluated, and test-retest reproducibility was examined. RESULTS: Optimal Venc was determined to be 3 cm/s, while recovery time and balanced SSFP flip angle within reasonable range had minimal effect on SNR efficiency. Venous T2 measured with TRU-VERA was highly correlated with T2 from TRUST (R2 = 0.90), and a conversion equation was established for further calibration to Yv. TRU-VERA sequences showed consistent Yv estimation with TRUPC (R2 = 0.64) and accelerated TRUPC (R2 = 0.79). Coefficient of variation was 0.84% for large veins and 2.49% for small veins, suggesting an excellent test-retest reproducibility. CONCLUSION: The proposed TRU-VERA sequence is a promising method for vessel-specific oxygenation assessment.

The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

Expression and Variations in EPO Associated with Oxygen Metabolism in Tibetan Sheep.

After a long period of adaptive evolution, Tibetan sheep have adapted to the plateau environment in terms of genetics, physiology and biochemistry, but the mechanism of hypoxia adaptation has not been fully elucidated, and the functional genes and molecular mechanisms regulating the hypoxia adaptation of Tibetan sheep need to be further studied. In this study, Tibetan sheep were selected as the research object, and the mRNA expression levels of the hypoxa-related gene EPO in heart, lung, kidney, liver, spleen and longissimus dorsi muscle of Hu sheep (100 m) and Tibetan sheep at different altitudes (2500 m, 3500 m, 4500 m) were assessed by RT-qPCR. The SNPs loci were detected by sequencing and Kompetitive Allele-Specific PCR (KASP) technology, then the correlation between genetic polymorphism and blood gas was analyzed. The results show that the expression of the EPO gene was the highest in the kidney, indicating that the expression of EPO gene had tissue differences. The expression levels of the EPO gene in the heart, lung and liver of Tibetan sheep at a 4500 m altitude were significantly higher than those in Hu sheep (p < 0.05), and the levels in the hearts of Tibetan sheep increased with the increase in altitude. Three mutations were identified in the EPO gene, the SNPs (g.855 A > C) in exon 1 and the SNPs (g.1985 T > G and g.2115 G > C) in exon 4, which were named EPO-SNP1, EPO-SNP2 and EPO-SNP3, respectively, and all three SNPs showed three genotypes. Correlation analysis showed that g.2115 G > C sites were significantly correlated with pO2 (p < 0.05), and haplotype combinations were significantly correlated with pO2 (p < 0.05). Thesee results suggest that the expression of the EPO gene is altitude-differentiated and organ-differentiated, and the EPO gene variants have significant effects on pO2, which may be beneficial to the adaptation of Tibetan sheep to hypoxia stress.

All Three AKT Isoforms Can Upregulate Oxygen Metabolism and Lactate Production in Human Hepatocellular Carcinoma Cell Lines.

Hepatocellular carcinoma (HCC), the main pathological type of liver cancer, is related to risk factors such as viral hepatitis, alcohol intake, and non-alcoholic fatty liver disease (NAFLD). The constitutive activation of the PI3K/AKT signaling pathway is common in HCC and has essential involvement in tumor progression. The serine/threonine kinase AKT has several downstream substrates, which have been implicated in the regulation of cellular metabolism. However, the contribution of each of the three AKT isoforms, i.e., AKT1, AKT2 and AKT3, to HCC metabolism has not been comprehensively investigated. In this study, we analyzed the functional role of AKT1, AKT2 and AKT3 in HCC metabolism. The overexpression of activated AKT1, AKT2 and AKT3 isoforms in the human HCC cell lines Hep3B and Huh7 resulted in higher oxygen consumption rate (OCR), ATP production, maximal respiration and spare respiratory capacity in comparison to vector-transduced cells. Vice versa, lentiviral vector-mediated knockdowns of each AKT isoform reduced OCR in both cell lines. Reduced OCR rates observed in the three AKT isoform knockdowns were associated with reduced extracellular acidification rates (ECAR) and reduced lactate production in both analyzed cell lines. Mechanistically, the downregulation of OCR by AKT isoform knockdowns correlated with an increased phosphorylation of the pyruvate dehydrogenase on Ser232, which negatively regulates the activity of this crucial gatekeeper of mitochondrial respiration. In summary, our data indicate that each of the three AKT isoforms is able to upregulate OCR, ECAR and lactate production independently of each other in human HCC cells through the regulation of the pyruvate dehydrogenase.

Glucose-oxygen coupling can serve as a biomarker for neuroinflammation-related genetic variants.

The single-nucleotide polymorphism rs3197999 in the macrophage-stimulating protein 1 gene is a missense variant. Studies have indicated that macrophage-stimulating protein 1 mediates neuronal loss and synaptic plasticity damage, and overexpression of the macrophage-stimulating protein 1 gene leads to the excessive activation of microglial cells, thereby resulting in an elevation of cerebral glucose metabolism. Traditional diagnostic models may be disrupted by neuroinflammation, making it difficult to predict the pathological status of patients solely based on single-modal images. We hypothesize that the macrophage-stimulating protein 1 rs3197999 single-nucleotide polymorphism may lead to imbalances in glucose and oxygen metabolism, thereby influencing cognitive resilience and the progression of Alzheimer's disease. In this study, we found that among 121 patients with mild cognitive impairment, carriers of the macrophage-stimulating protein 1 rs3197999 risk allele showed a significant reduction in the coupling of glucose and oxygen metabolism in the dorsolateral prefrontal cortex region. However, the rs3197999 variant did not induce significant differences in glucose metabolism and neuronal activity signals. Furthermore, the rs3197999 risk allele correlated with a higher rate of increase in clinical dementia score, mediated by the coupling of glucose and oxygen metabolism.

Validation of a new 3D quantitative BOLD based cerebral oxygen extraction mapping.

Quantitative BOLD (qBOLD) MRI allows evaluation of oxidative metabolism of the brain based purely on an endogenous contrast mechanism. The method quantifies deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), yielding oxygen extraction fraction (OEF), and along with a separate measurement of cerebral blood flow, cerebral metabolic rate of oxygen (CMRO2) maps. Here, we evaluated our recently reported 3D qBOLD method that rectifies a number of deficiencies in prior qBOLD approaches in terms of repeat reproducibility and sensitivity to hypercapnia on the metabolic parameters, and in comparison to dual-gas calibrated BOLD (cBOLD) MRI for determining resting-state oxygen metabolism. Results suggested no significant difference between test-retest qBOLD scans in either DBV and OEF. Exposure to hypercapnia yielded group averages of 38 and 28% for OEF and 151 and 146 µmol/min/100 g for CMRO2 in gray matter at baseline and hypercapnia, respectively. The decrease of OEF during hypercapnia was significant (p ≪ 0.01), whereas CMRO2 did not change significantly (p = 0.25). Finally, baseline OEF (37 vs. 39%) and CMRO2 (153 vs. 145 µmol/min/100 g) in gray matter using qBOLD and dual-gas cBOLD were found to be in good agreement with literature values, and were not significantly different from each other (p > 0.1).

First implementation of dynamic oxygen-17 (17O) magnetic resonance imaging at 7 Tesla during neuronal stimulation in the human brain.

OBJECTIVE: First implementation of dynamic oxygen-17 (17O) MRI at 7 Tesla (T) during neuronal stimulation in the human brain. METHODS: Five healthy volunteers underwent a three-phase 17O gas (17O2) inhalation experiment. Combined right-side visual stimulus and right-hand finger tapping were used to achieve neuronal stimulation in the left cerebral hemisphere. Data analysis included the evaluation of the relative partial volume (PV)-corrected time evolution of absolute 17O water (H217O) concentration and of the relative signal evolution without PV correction. Statistical analysis was performed using a one-tailed paired t test. Blood oxygen level-dependent (BOLD) experiments were performed to validate the stimulation paradigm. RESULTS: The BOLD maps showed significant activity in the stimulated left visual and sensorimotor cortex compared to the non-stimulated right side. PV correction of 17O MR data resulted in high signal fluctuations with a noise level of 10% due to small regions of interest (ROI), impeding further quantitative analysis. Statistical evaluation of the relative H217O signal with PV correction (p = 0.168) and without (p = 0.382) did not show significant difference between the stimulated left and non-stimulated right sensorimotor ROI. DISCUSSION: The change of cerebral oxygen metabolism induced by sensorimotor and visual stimulation is not large enough to be reliably detected with the current setup and methodology of dynamic 17O MRI at 7 T.

MRI-based quantification of whole-organ renal metabolic rate of oxygen.

During the early stages of diabetes, kidney oxygen utilization increases. The mismatch between oxygen demand and supply contributes to tissue hypoxia, a key driver of chronic kidney disease. Thus, whole-organ renal metabolic rate of oxygen (rMRO2 ) is a potentially valuable biomarker of kidney function. The key parameters required to determine rMRO2 include the renal blood flow rate (RBF) in the feeding artery and oxygen saturation in the draining renal vein (SvO2 ). However, there is currently no noninvasive method to quantify rMRO2 in absolute physiologic units. Here, a new MRI pulse sequence, Kidney Metabolism of Oxygen via T2 and Interleaved Velocity Encoding (K-MOTIVE), is described, along with evaluation of its performance in the human kidney in vivo. K-MOTIVE interleaves a phase-contrast module before a background-suppressed T2 -prepared balanced steady-state-free-precession (bSSFP) readout to measure RBF and SvO2 in a single breath-hold period of 22 s, yielding rMRO2 via Fick's principle. Variants of K-MOTIVE to evaluate alternative bSSFP readout strategies were studied. Kidney mass was manually determined from multislice gradient recalled echo images. Healthy subjects were recruited to quantify rMRO2 of the left kidney at 3-T field strength (N = 15). Assessments of repeat reproducibility and comparisons with individual measurements of RBF and SvO2 were performed, and the method's sensitivity was evaluated with a high-protein meal challenge (N = 8). K-MOTIVE yielded the following metabolic parameters: T2  = 157 ± 19 ms; SvO2  = 92% ± 6%; RBF = 400 ± 110 mL/min; and rMRO2  = 114 ± 117(µmol O2 /min)/100 g tissue. Reproducibility studies of T2 and RBF (parameters directly measured by K-MOTIVE) resulted in coefficients of variation less than 10% and intraclass correlation coefficients more than 0.75. The high-protein meal elicited an increase in rMRO2 , which was corroborated by serum biomarkers. The K-MOTIVE sequence measures SvO2 and RBF, the parameters necessary to quantify whole-organ rMRO2 , in a single breath-hold. The present work demonstrates that rMRO2 quantification is feasible with good reproducibility. rMRO2 is a potentially valuable physiological biomarker.

Quantification of whole-organ individual and bilateral renal metabolic rate of oxygen.

PURPOSE: Renal metabolic rate of oxygen (rMRO2 ) is a potentially important biomarker of kidney function. The key parameters for rMRO2 quantification include blood flow rate (BFR) and venous oxygen saturation (SvO2 ) in a draining vessel. Previous approaches to quantify renal metabolism have focused on the single organ. Here, both kidneys are considered as one unit to quantify bilateral rMRO2 . A pulse sequence to facilitate bilateral rMRO2 quantification is introduced. METHODS: To quantify bilateral rMRO2 , measurements of BFR and SvO2 are made along the inferior vena cava (IVC) at suprarenal and infrarenal locations. From the continuity equation, these four parameters can be related to derive an expression for bilateral rMRO2 . The recently reported K-MOTIVE pulse sequence was implemented at four locations: left kidney, right kidney, suprarenal IVC, and infrarenal IVC. A dual-band variant of K-MOTIVE (db-K-MOTIVE) was developed by incorporating simultaneous-multi-slice imaging principles. The sequence simultaneously measures BFR and SvO2 at suprarenal and infrarenal locations in a single pass of 21 s, yielding bilateral rMRO2 . RESULTS: SvO2 and BFR are higher in suprarenal versus infrarenal IVC, and the renal veins are highly oxygenated (SvO2 >90%). Bilateral rMRO2 quantified in 10 healthy subjects (8 M, 30 ± 8 y) was found to be 291 ± 247 and 349 ± 300 (µmolO2 /min)/100 g, derived from K-MOTIVE and db-K-MOTIVE, respectively. In comparison, total rMRO2 from combining left and right was 329 ± 273 (µmolO2 /min)/100 g. CONCLUSION: The present work demonstrates that bilateral rMRO2 quantification is feasible with fair reproducibility and physiological plausibility. The indirect method is a promising approach to compute bilateral rMRO2 when individual rMRO2 quantification is difficult.

Small animal PET with spontaneous inhalation of 15O-labelled oxygen gases: Longitudinal assessment of cerebral oxygen metabolism in a rat model of neonatal hypoxic-ischaemic encephalopathy.

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO2.This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes.

Oxygen metabolism abnormality and Alzheimer's disease: An update.

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living in a high-altitude habitat, cardiovascular and cerebrovascular diseases, and chronic obstructive sleep apnea. Chronic hypoxia has been identified as a significant risk factor for AD, showing an aggravation of various pathological components of AD, such as amyloid ß-protein (Aß) metabolism, tau phosphorylation, mitochondrial dysfunction, and neuroinflammation. It is known that hypoxia and excessive hyperoxia can both result in oxidative stress and mitochondrial dysfunction. Oxidative stress and mitochondrial dysfunction can increase Aß and tau phosphorylation, and Aß and tau proteins can lead to redox imbalance, thus forming a vicious cycle and exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) is a non-invasive intervention known for its capacity to significantly enhance cerebral oxygenation levels, which can significantly attenuate Aß aggregation, tau phosphorylation, and neuroinflammation. However, further investigation is imperative to determine the optimal oxygen pressure, duration of exposure, and frequency of HBOT sessions. In this review, we explore the prospects of oxygen metabolism in AD, with the aim of enhancing our understanding of the underlying molecular mechanisms in AD. Current research aimed at attenuating abnormalities in oxygen metabolism holds promise for providing novel therapeutic approaches for AD.

Heat stress affects dairy cow health status through blood oxygen availability.

BACKGROUND: Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows, resulting in low milk quality and yield. In animals, oxygen is involved in many physiological and metabolic processes, but the effects of HS on oxygen metabolism remain unclear. Thus, the current study aimed to investigate how oxygen metabolism plays a role in health status of dairy cows by measuring the milk yield, milk composition, and blood biochemical variables of cows under different levels of HS: none (No-HS), mild (Mild-HS), and moderate HS (Mod-HS). RESULTS: The HS significantly increased rectal temperature (Ptreat < 0.01) and respiration rate (Ptreat < 0.01). Under Mod-HS, greater Na+ (P < 0.05) and lower total CO2, and pH (P < 0.05) were observed relative to those under No-HS and Mild-HS. Oxygen concentrations in both coccygeal artery and mammary vein (Ptreat < 0.01) were lower under Mod-HS than under No-HS. Coccygeal vein concentrations of heat shock protein 90 (HSP90) (P < 0.05) increased during Mod-HS compared with those in cows under No-HS. Malondialdehyde increased during Mod-HS, and glutathione peroxidase (P < 0.01) increased during Mild-HS. Coccygeal vein concentrations of vascular endothelial growth factor (P < 0.01), heme oxygenase-1 (P < 0.01), and hypoxia-inducible factor 1α (P < 0.01) were greater in cows under Mod-HS than those under No-HS. Red blood cell count (P < 0.01) and hemoglobin concentration (P < 0.01) were lower in the coccygeal vein of dairy cows under Mild- and Mod-HS than those of cows under No-HS. CONCLUSIONS: Exposure to HS negatively impacts the health status and lactation performance of dairy cows by limiting oxygen metabolism and transportation. However, the specific mechanism by which HS affects mammary function in cows remains unclear and requires further exploration.

Alleviation effect of GR24, a strigolactone analogue, on low-nitrogen stress in Malus baccata seedlings.

To investigate the efficacy of foliar application of GR24, a strigolactone analogue, in alleviating low-nitrogen stress in Malus baccata, we applied GR24 with different concentrations (0, 1, 5, 10, and 20 µmol·L-1) to leaves of plants under low nitrogen stress. We evaluated the changes in photosynthetic characteristics of leaves, reactive oxygen metabolism, and nitrogen assimilation in roots. The results showed that shoot biomass of seedling significantly decreased and root-shoot ratio increased under low-nitrogen stress. The chlorophyll contents decreased, the carotenoid content increased, and the photosynthetic activity decreased. The activities of superoxide dismutase and catalase enzymes in roots changed little, while the activities of peroxidase and ascorbic acid peroxidase enzymes, along with the levels of soluble sugar, free proline, and reactive oxygen species showed a significant increase, and the soluble protein content decreased. The NO3- content in roots decreased, the NH4+ content increased, while activities of nitrate reductase and glutamine synthase decreased. Compared to the control group without GR24 application, foliar sprays of 10 and 20 µmol·L-1 GR24 under both normal and low-nitrogen increased biomass and root-shoot ratio to varying degrees. Additionally, GR24 application increased chlorophyll content, photosynthesis indices (net photosynthetic rate, transpiration rate and stomatal conductance), and fluorescence (maximum photochemical efficiency of PSⅡ and quantum yield of electron transfer per unit area) performance parameters, as well as the contents of osmotic regulation substances (soluble protein, soluble sugar, and free proline) and glutamine synthase activity. Application of 10 and 20 µmol·L-1 GR24 under low-nitrogen stress decreased carotenoid, reactive oxygen species, and NH4+ contents, while increased the activities of antioxidases and key enzymes in nitrogen metabolism (nitrate reductase and glutamine synthase) and NO3- content. The 10 µmol·L-1 GR24 treatment was the most effective in alleviating low nitrogen stress, which has potential for application in apple orchards with low nitrogen soil.

Quantification of regional CMRO2 in human brain using dynamic 17O-MRI at 3T.

OBJECTIVE: To investigate the feasibility of cerebral metabolic rate of oxygen consumption (CMRO2) measurements with MRI at 3 Tesla in different brain regions. METHODS: CMRO2 represents a key indicator of the physiological state of brain tissue. Dynamic 17O-MRI with inhalation of isotopically enriched 17O gas has been used to quantify global CMRO2 in brain white (WM) and gray matter (GM). However, global CMRO2 can only reflect the overall oxygen metabolism of the brain and cannot provide enough information on local tissue oxygen metabolism. To investigate the feasibility of determination of regional CMRO2 at a clinical 3 T MRI system, CMRO2 values in frontal, parietal and occipital WM and GM were determined in 5 healthy volunteers and compared to evaluate the regional differences of oxygen metabolism in WM and GM. Additionally, regional CMRO2 values were determined in deep brain structures including thalamus, dorsal striatum, caudate nucleus and insula cortex and in the cerebella, and compared with literature values from 15O-PET studies. RESULTS: In cortical GM the determined CMRO2 values were in good agreement with the literature, whereas values in WM were about 32-48% higher than literature values. Regional analysis revealed a significantly higher CMRO2 in the occipital GM compared to the frontal and parietal GM. By contrast, no significant difference of CMRO2 was observed across the WM. In addition, CMRO2 in deep brain structures was lower compared to literature values and in the cerebella a good hemispheric symmetry of the tissue oxygen metabolism was found. CONCLUSION: Dynamic 17O-MRI enables direct, non-invasive determination of regional CMRO2 in brain structures in healthy volunteers at 3T.

First application of dynamic oxygen-17 magnetic resonance imaging at 7 Tesla in a patient with early subacute stroke.

Dynamic oxygen-17 (17O) magnetic resonance imaging (MRI) is an imaging method that enables a direct and non-invasive assessment of cerebral oxygen metabolism and thus potentially the distinction between viable and non-viable tissue employing a three-phase inhalation experiment. The purpose of this investigation was the first application of dynamic 17O MRI at 7 Tesla (T) in a patient with stroke. In this proof-of-concept experiment, dynamic 17O MRI was applied during 17O inhalation in a patient with early subacute stroke. The analysis of the relative 17O water (H217O) signal for the affected stroke region compared to the healthy contralateral side revealed no significant difference. However, the technical feasibility of 17O MRI has been demonstrated paving the way for future investigations in neurovascular diseases.

Oxygen metabolism analysis of a single organoid for non-invasive discrimination of cancer subpopulations with different growth capabilities.

Heterogeneous nature is a pivotal aspect of cancer, rendering treatment problematic and frequently resulting in recurrence. Therefore, advanced techniques for identifying subpopulations of a tumour in an intact state are essential to develop novel screening platforms that can reveal differences in treatment response among subpopulations. Herein, we conducted a non-invasive analysis of oxygen metabolism on multiple subpopulations of patient-derived organoids, examining its potential utility for non-destructive identification of subpopulations. We utilised scanning electrochemical microscopy (SECM) for non-invasive analysis of oxygen metabolism. As models of tumours with heterogeneous subpopulations, we used patient-derived cancer organoids with a distinct growth potential established using the cancer tissue-originated spheroid methodology. Scanning electrochemical microscopy measurements enabled the analysis of the oxygen consumption rate (OCR) for individual organoids as small as 100 µm in diameter and could detect the heterogeneity amongst studied subpopulations, which was not observed in conventional colorectal cancer cell lines. Furthermore, our oxygen metabolism analysis of pre-isolated subpopulations with a slow growth potential revealed that oxygen consumption rate may reflect differences in the growth rate of organoids. Although the proposed technique currently lacks single-cell level sensitivity, the variability of oxygen metabolism across tumour subpopulations is expected to serve as an important indicator for the discrimination of tumour subpopulations and construction of novel drug screening platforms in the future.

The Effects of Combined 1-Methylcyclopropene and Melatonin Treatment on the Quality Characteristics and Active Oxygen Metabolism of Mango Fruit during Storage.

In this study, mango fruit (Tainong No. 1) was treated with either 0.1 mg/L 1-methylcyclopropene (1-MCP) alone or with a combination of 0.1 mg/L 1-MCP and 0.2 mM melatonin (MT). The mango fruit was then stored for 10 days at 25 °C and 85-90% relative humidity. Quality characteristics and the active oxygen metabolism of postharvest mangoes were evaluated every 2 days. Compared to untreated mango fruit, those with the treatments of 1-MCP alone or 1-MCP + MT had a better appearance and higher levels of soluble sugar, ascorbic acid, and titratable acidity. Moreover, these treatments prevented the loss of fruit firmness, successfully delayed the escalation of a* and b* values, and reduced malondialdehyde content and superoxide anion generation rate. After 10 days of storage, mango fruit treated by 1-MCP alone or 1-MCP + MT exhibited increased activities of antioxidant enzymes such as ascorbate peroxidase, catalase, superoxide dismutase, and other peroxidases; nevertheless, the two treatment protocols maintained higher mango total phenolic content only at the later stage of storage. These findings suggest that mango fruit treated with 1-MCP alone or with 1-MCP + MT improves the quality characteristics and antioxidant activities. Moreover, compared to 1-MCP treatment alone, 1-MCP + MT-treated mangoes exhibited higher quality and a stronger regulation of active metabolism during storage.