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Phototoxicity poses a substantial challenge in photodynamic therapy, resulting in intolerable skin damage, visual impairment, and reduced quality of life. Current coping strategies, primarily focus on avoiding inappropriate photoactivation and developing targeted photosensitizers, have not effectively addressed this problem. Hence, this study aims to develop a “sunlight‐friendly” photodynamic therapy strategy. Here, 1‐methoxyphenazine methosulfate (MPMS) is innovatively identified as a key substance in achieving modified oxygen metabolism. MPMS demonstrates efficient catalytic shuttling under abnormal intracellular H2O2 levels, introducing a novel protective approach for oxygen metabolism and numerous life processes. By controlling MPMS administration, the switch of the photosensitizer states between “ON” (killing tumor cells) and “OFF” (safeguarding normal cells) can be achieved. This approach effectively mitigated phototoxicity and holds the potential for widespread clinical application. [ABSTRACT FROM AUTHOR]

Purpose: We studied the effect of O2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD). Methods: Thirteen patients (age 66 ± 10 yr, 7 males) with ILD (total lung capacity, 71% ± 22% predicted; carbon monoxide diffusion capacity, 44% ± 16% predicted) and 13 healthy individuals (age 50 ± 17 yr, 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work rate (WR) tests at 80% of the WR at the gas exchange threshold. Tests breathing room air (RA; 21% O2) were compared with tests performed breathing 30% O2. Oxygen uptake (V̇O2) kinetics were calculated from the constant WR test results. Results: In the ILD group, peak WR, peak V̇O2, and V̇O2 at the gas exchange threshold improved significantly when breathing 30% O2 compared with RA (mean ± SD, 75 ± 26 vs 66 ± 23 W, 17 ± 4 vs 15 ± 2 mL·kg-1·min-1, and 932 ± 245 vs 854 ± 232 mL·min-1; P = 0.004, P = 0.001, and P = 0.01, respectively). O2 saturation (SpO2%) at peak exercise was higher with 30% O2 (97% ± 4% vs 88% ± 9%, P = 0.002). The time constant (tau) of V̇O2 kinetics was faster in ILD patients while breathing 30% O2 (41 ± 10 s) compared with RA (52 ± 14 s, P = 0.003). There was a negative linear relation between tau and SpO2% with RA (r = -0.76, P = 0.006) and while breathing 30% O2 (r = -0.68, P = 0.02). Conclusions: Using a clinically applicable level of O2 supplementation (30%) improved maximal, aerobic exercise capacity and V̇O2 kinetics in ILD patients, likely due to increased blood O2 content subsequently increasing the O2 delivery to the working muscles. [ABSTRACT FROM AUTHOR]

Introduction: The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. Methods: Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. Results: The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. Conclusion: The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future. [ABSTRACT FROM AUTHOR]

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25–160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response. Methods: Patients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP). Results: MAP was higher in the research group than in the control group at T1 and T2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO2, CERO2, and rSO2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05). Conclusion: NT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Early cerebral and body iron dysregulation and accumulation interact with AD pathology, particularly in the precuneus, a crucial functional hub in cognitive functions. Quantitative susceptibility mapping (QSM), a novel post‐processing approach, provides insights into tissue iron levels and cerebral oxygen metabolism and reveals abnormal iron accumulation early in AD. Increased iron deposition in the precuneus can lead to oxidative stress, neuroinflammation, and accelerated neurodegeneration. Metabolic disorders (diabetes, non‐alcoholic fatty liver disease (NAFLD), and obesity), genetic factors, and small vessel pathology contribute to abnormal iron accumulation in the precuneus. Therefore, in line with the growing body of literature in the precuneus region of patients with AD, QSM as a neuroimaging method could serve as a non‐invasive biomarker to track disease progression, complement other imaging modalities, and aid in early AD diagnosis and monitoring. [ABSTRACT FROM AUTHOR]

Objective Cerebral oximetry using near-infrared spectroscopy (NIRS) is a noninvasive optical technology widely used in neonatology. The present study aimed to define reference ranges for cerebral tissue oxygen saturation (crSO 2) with a new four-wavelength NIRS device, Masimo O3 oximeter, during immediate transition after birth and compare values with those obtained previously with NIRO 200NX ®. Study Design This was a prospective observational study using Masimo O3 device to measure crSO 2 and regional cerebral fractional tissue oxygen extraction (cFTOE) in healthy term newborns delivered by primary cesarean section, during the 15 minutes after cord clamping. The neonates who required any medical support were excluded. The NIRS sensor was placed on the right forehead. Peripheral oxygen saturation and heart rate were continuously measured by pulse oximetry. Previous studies which established centiles for crSO 2 with NIRO 200NX were used for comparison. Results A total of 44 newborns were included. The median crSO 2 and cFTOE (interquartile range) at 2, 5, and 7 minutes was 54% (49–54), 71% (64–86), and 79% (73–84) and 0,25 (0,18–0,33), 0,19 (0,15–0,23), and 0,16 (0,12–0,21), respectively, with no further changes afterwards. The crSO 2 measurements were significantly higher with Masimo O3 compared with NIRO-200NX. Conclusion The present observational study presented reference ranges for crSO 2 and cFTOE measured with Masimo O3 oximeter during the immediate neonatal transition. Values obtained with O3 were higher than those obtained with other oximeters. For this reason, crSO 2 is device-specific so there must be known reference values for each oximeter to define therapeutic interventions based on crSO 2 and assess cerebral oxygenation in clinical studies. Key Points Masimo O3 uses four wavelengths to measure regional oxygen saturation value. O3 values of crSO 2 and cFTOE differ with other neonatal oximeters at birth. Knowledge of reference range of O3 at birth is essential to guide resuscitation. [ABSTRACT FROM AUTHOR]

Although magnetism undoubtedly influences life on Earth, the science behind biological magnetic sensing is largely a mystery, and it has proved challenging, especially in the life sciences, to harness the interactions of magnetic fields (MFs) with matter to achieve specific ends. Using the well-established radical pair (RP) mechanism, we here demonstrate a bottom-up strategy for the exploitation of MF effects in living cells by translating knowledge from studies of RP reactions performed in vitro. We found an unprecedented MF dependence of the reactivity of singlet oxygen (1O2) towards electron-rich substrates (S) such as anthracene, lipids and iodide, in which [ S ˙+ O2˙−] RPs are formed as a basis for MFs influencing molecular redox events in biological systems. The close similarity of the observed MF effects on the biologically relevant process of lipid peroxidation in solution, in membrane mimics and in living cells, shows that MFs can reliably be used to manipulate 1O2-induced cytotoxicity and cell-apoptosis-related protein expression. These findings led to a 'proof-of-concept' study on MF-assisted photodynamic therapy in vivo , highlighting the potential of MFs as a non-invasive tool for controlling cellular events. [ABSTRACT FROM AUTHOR]

Objective: The effect of continuous topical oxygen therapy (cTOT) on Pseudomonas aeruginosa biofilm gene transcription profiles following inoculation onto porcine skin, using a customised molecular assay was determined. Method: Sterilised porcine skin explants were inoculated with Pseudomonas aeruginosa in triplicate: 0 hours as negative control; 24 hours cTOT device on; 24 hours cTOT device off. The oxygen delivery system of the cTOT device was applied to the inoculated tissue and covered with a semi-occlusive dressing. All samples were incubated at 37±2°C for 24 hours, with the 0 hours negative control inoculated porcine skin samples recovered immediately. Planktonic suspensions and porcine skin biopsy samples were taken at 0 hours and 24 hours. Samples were processed and quantifiably assessed using gene specific reverse transcription-quantitative polymerase chain reaction assays for a panel of eight Pseudomonas aeruginosa genes (16S, pelA, pslA, rsaL, pcrV, pscQ, acpP, cbrA) associated with biofilm formation, quorum sensing, protein secretion/translocation and metabolism. Results: Transcriptional upregulation of pelA, pcrV and acpP, responsible for intracellular adhesion, needletip protein production for type-3 secretion systems and fatty acid synthesis during proliferation, respectively, was observed when the cTOT device was switched on compared to when the device was switched off. Data suggest increased metabolic activity within bacterial cells following cTOT treatment. Conclusion: cTOT is an adjunctive therapy that supports faster healing and pain reduction in non-healing hypoxic wounds. Oxygen has previously been shown to increase susceptibility of biofilms to antibiotics through enhancing metabolism. Observed gene expression changes highlighted the impact of cTOT on biofilms, potentially influencing antimicrobial treatment success in wounds. Further in vitro and clinical investigations are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the effects of integrated blood purification on haemodynamics and oxygen metabolism in children with severe sepsis.MethodsClinical data of 12 children with severe sepsis admitted to the pediatric intensive care unit of our hospital between October 2021 and June 2022 were retrospectively analyzed. All patients were treated with integrated blood purification, and changes in haemodynamic parameters, including heart rate, blood pressure, mean arterial pressure and cardiac output, and oxygen metabolism parameters (blood lactic acid, oxygen delivery, oxygen consumption and oxygen extraction rate) were observed before and after treatment.ResultsThe heart rate (134[106,160] vs 111[101,128], p = 0.037), central venous pressure (9[7,10] vs 8[7,9], p = 0.04), stroke output (28[18,43] vs 21[15,31], p = 0.01), blood lactate (3.3[2,4] vs 2.5[1.3,3.6], p = 0.015), oxygen consumption (165.99[121.44,230.31] vs 124.18[82.51,162.86], p = 0.041) and oxygen extraction rate (38.83[31.87,44.62] vs 28.67[21.05,32.72], p = 0.019) were decreased, whereas systolic blood pressure (97[83,104] vs 107[94,116], p = 0.033) and central venous oxygen pressure (32[29, 37] vs 39[34,46], p = 0.005) were increased in the children after treatment compared with before treatment. There were no statistically significant differences in diastolic blood pressure, mean arterial pressure, cardiac output, arterial oxygen pressure and oxygen delivery before and after treatment (all p > 0.05).ConclusionIntegrated blood purification can improve haemodynamic and oxygen metabolism parameters in children with severe sepsis, with a high value in clinical application.

Introduction: Before tracheal intubation, it is essential to provide sufficient oxygen reserve for emergency patients with full stomachs. Recent studies have demonstrated that high-flow nasal oxygen (HFNO) effectively pre-oxygenates and prolongs apneic oxygenation during tracheal intubation. Despite its effectiveness, the use of HFNO remains controversial due to concerns regarding carbon dioxide clearance. The air leakage and unknown upper airway obstruction during HFNO therapy cause reduced oxygen flow above the vocal cords, possibly weaken the carbon dioxide clearance. Methods: Patients requiring emergency surgery who had fasted < 8 h and not drunk < 2 h were randomly assigned to the high-flow group, who received 100% oxygen at 30–60 L/min through nasopharyngeal airway (NPA), or the mask group, who received 100% oxygen at 8 L/min. PaO2 and PaCO2 were measured immediately before pre-oxygenation (T0), anesthesia induction (T1), tracheal intubation (T2), and mechanical ventilation (T3). The gastric antrum's cross-sectional area (CSA) was measured using ultrasound technology at T0, T1, and T3. Details of complications, including hypoxemia, reflux, nasopharyngeal bleeding, postoperative pulmonary infection, postoperative nausea and vomiting (PONV), and postoperative nasopharyngeal pain, were recorded. The primary outcomes were PaCO2 measured at T1, T2, and T3. The secondary outcomes included PaO2 at T1, T2, and T3, CSA at T1 and T3, and complications happened during this trial. Results: Pre-oxygenation was administered by high-flow oxygen through NPA (n = 58) or facemask (n = 57) to 115 patients. The mean (SD) PaCO2 was 32.3 (6.7) mmHg in the high-flow group and 34.6 (5.2) mmHg in the mask group (P = 0.045) at T1, 45.0 (5.5) mmHg and 49.4 (4.6) mmHg (P < 0.001) at T2, and 47.9 (5.1) mmHg and 52.9 (4.6) mmHg (P < 0.001) at T3, respectively. The median ([IQR] [range]) PaO2 in the high-flow and mask groups was 404.5 (329.1–458.1 [159.8–552.9]) mmHg and 358.9 (274.0–413.3 [129.0–539.1]) mmHg (P = 0.007) at T1, 343.0 (251.6–428.7 [73.9–522.1]) mmHg and 258.3 (162.5–347.5 [56.0–481.0]) mmHg (P < 0.001) at T2, and 333.5 (229.9–411.4 [60.5–492.4]) mmHg and 149.8 (87.0–246.6 [51.2–447.5]) mmHg (P < 0.001) at T3, respectively. The CSA in the high-flow and mask groups was 371.9 (287.4–557.9 [129.0–991.2]) mm2 and 386.8 (292.0–537.3 [88.3–1651.7]) mm2 at T1 (P = 0.920) and 452.6 (343.7–618.4 [161.6–988.1]) mm2 and 385.6 (306.3–562.0 [105.5–922.9]) mm2 at T3 (P = 0.173), respectively. The number (proportion) of complications in the high-flow and mask groups is shown below: hypoxemia: 1 (1.7%) vs. 9 (15.8%, P = 0.019); reflux: 0 (0%) vs. 0 (0%); nasopharyngeal bleeding: 1 (1.7%) vs. 0 (0%, P = 1.000); pulmonary infection: 4 (6.9%) vs. 3 (5.3%, P = 1.000); PONV: 4 (6.9%) vs. 4 (7.0%, P = 1.000), and nasopharyngeal pain: 0 (0%) vs. 0 (0%). Conclusions: Compared to facemasks, pre-oxygenation with high-flow oxygen through NPA offers improved carbon dioxide clearance and enhanced oxygenation prior to tracheal intubation in patients undergoing emergency surgery, while the risk of gastric inflation had not been ruled out. Trial registration: This trial was registered prospectively at the Chinese Clinical Research Registry on 26/4/2022 (Registration number: ChiCTR2200059192). [ABSTRACT FROM AUTHOR]

Purpose: Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. Methods: Our algorithm was built systematically with 4 components – machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. Results: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. Conclusion: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery. [ABSTRACT FROM AUTHOR]

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21 ± 2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean ± standard deviation. There was a significant main effect of drink (PL < BRJ; P = 0.042, ηp2 = 0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL < BRJ; P = 0.03; ηp2= 0.197; 20%–50% and 90% LOT). BRJ did not influence oxygen delivery (P = 0.893, ηp2 = 0.002), forearm blood flow (P = 0.589, ηp2 = 0.03) (forearm vascular conductance (P = 0.262, ηp2 = 0.124), mean arterial pressure (P = 0.254,ηp2 = 0.128)), oxygen consumption (P = 0.194, ηp2 = 0.179) or LOT (P = 0.432, d = 0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity. [ABSTRACT FROM AUTHOR]

Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. Prospective observational study of infants born 30–34 weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, and at seven days. Subjects were divided into gestational age (GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0–12 h, 12–24 h, 24–48 h, 48–72 h, and one week of life. Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to 91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use when monitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Early characterization of the isocitrate dehydrogenase (IDHIDH) gene mutation status of glioma is crucial for personalized decision making and prognosis in clinical neurooncological treatment. Based on the known differences in energy metabolism between IDHIDH-mutated and IDHIDH-wildtype gliomas, we assessed physio-metabolic magnetic resonance imaging-based measures along with machine learning for potential reliable presurgical characterization of IDHIDH gene status. Traditional machine learning algorithms and simple deep learning models trained in analyzing physio-metabolic parameters demonstrated the best performance in classifying the IDHIDH gene status of gliomas in independent internal testing. In contrast, external testing revealed that traditional machine learning models trained on clinical MRI data had higher accuracy compared to physio-metabolic algorithms, reflecting differences in data acquisition methodology between the two sites. Our results outline the necessity of independent internal and external testing, thus calling for standardized and robust protocols for clinical MRI-driven AI applications. The mutational status of the isocitrate dehydrogenase (IDH) gene plays a key role in the treatment of glioma patients because it is known to affect energy metabolism pathways relevant to glioma. Physio-metabolic magnetic resonance imaging (MRI) enables the non-invasive analysis of oxygen metabolism and tissue hypoxia as well as associated neovascularization and microvascular architecture. However, evaluating such complex neuroimaging data requires computational support. Traditional machine learning algorithms and simple deep learning models were trained with radiomic features from clinical MRI (cMRI) or physio-metabolic MRI data. A total of 215 patients (first center: 166 participants + 16 participants for independent internal testing of the algorithms versus second site: 33 participants for independent external testing) were enrolled using two different physio-metabolic MRI protocols. The algorithms trained with physio-metabolic data demonstrated the best classification performance in independent internal testing: precision, 91.7%; accuracy, 87.5%; area under the receiver operating curve (AUROC), 0.979. In external testing, traditional machine learning models trained with cMRI data exhibited the best IDH classification results: precision, 84.9%; accuracy, 81.8%; and AUROC, 0.879. The poor performance for the physio-metabolic MRI approach appears to be explainable by site-dependent differences in data acquisition methodologies. The physio-metabolic MRI approach potentially supports reliable classification of IDH gene status in the presurgical stage of glioma patients. However, non-standardized protocols limit the level of evidence and underlie the need for a reproducible framework of data acquisition techniques. [ABSTRACT FROM AUTHOR]

Objective Hypoxic-ischemic encephalopathy (HIE) affects millions of newborns annually, especially in low-resource settings. Real-time monitoring of hypoxic-ischemic brain damage is urgently needed for assessment of severity and management of neonates with birth asphyxia. Aim of the work is monitoring of near-infrared spectroscopy (NIRS)-measured cerebral regional oxygen saturation (cRSO 2) and cerebral fractional tissue oxygen extraction (FTOE) in neonates after birth asphyxia in relation to their clinical course. Study Design Forty asphyxiated-term and near-term neonates with mild to severe HIE admitted at neonatal intensive care unit of Alexandria University Maternity Hospital from March to October 2019, received therapeutic hypothermia (TH) and had continuous NIRS monitoring of cRSO 2 for 72 hours. Infants were categorized into HIE with seizing and nonseizing groups, and abnormal and normal magnetic resonance imaging (MRI) groups. Results Clinical seizures (CS) occurred in 15 (37.5%) of HIE neonates and 13.3% of them died (n = 2). In the current study, significantly higher cRSO 2 and lower FTOE values were found in the seizing infants as compared with nonseizing group (p < 0.001). NIRS-measured day 2-cRSO 2 and day 1-FTOE were associated with CS in newborns with HIE and day 1-cRSO 2 and FTOE were associated with abnormal MRI at 1 month of age. cRSO 2 values were found to correlate positively with initial Thompson score especially in days 1 and 2. Further, neonates with CS were more likely to have MRI abnormalities at follow-up. Conclusion NIRS measures may highlight differences between asphyxiated neonates who develop CS or later MRI abnormalities and those who do not. Key Points Day 1 FTOE is the early and sensitive predictor for both clinical seizures and abnormal MRI. Cerebral oxygenation metrics help in selecting patients in urgent need of an early MRI scan. Cerebral oxygenation metrics can be used hand in hand with clinical assessment using Thompson score at admission to select patient candidate for therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Simple Summary: The hypoxa-related gene EPO is a key factor in erythropoiesis. In high-altitude indigenous species, the expression of and variations in the EPO gene are closely related to changes of altitude (oxygen concentration). In this study, the mRNA expression levels of gene EPO in different tissues and organs of Hu sheep (100 m) and Tibetan sheep at different altitudes (2500 m, 3500 m, 4500 m) were detected by RT-qPCR, and Kompetitive Allele-Specific PCR (KASP) was used to study the effects of EPO variation on plateau hypoxia adaptation in Tibetan sheep. The results suggest that variations in the EPO gene were correlated with some blood gas indexes of Tibetan sheep, and the expression of the EPO gene was related to changes in altitude. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sufficient delivery of oxygen and metabolic substrates, together with removal of waste products, are key elements of muscle performance. Capillaries are the primary site for this exchange in skeletal muscle and the degree of muscle capillarization affects diffusion conditions by influencing mean transit time, capillary surface area and diffusion distance. Muscle capillarization may thus represent a limiting factor for performance. Exercise training increases the number of capillaries per muscle fiber by about 10%–20% within a few weeks in untrained subjects, whereas capillary growth progresses more slowly in well‐trained endurance athletes. Studies show that capillaries are tortuous, situated along and across the length of the fibers with an arrangement related to muscle fascicles. Although direct data is lacking, it is possible that years of training not only enhances capillary density but also optimizes the positioning of capillaries, to further improve the diffusion conditions. Muscle capillarization has been shown to increase oxygen extraction during exercise in humans, but direct evidence for a causal link between increased muscle capillarization and performance is scarce. This review covers current knowledge on the implications of muscle capillarization for oxygen and glucose uptake as well as performance. A brief overview of the process of capillary growth and of physical factors, inherent to exercise, which promote angiogenesis, provides the foundation for a discussion on how different training modalities may influence muscle capillary growth. Finally, we identify three areas for future research on the role of capillarization for exercise performance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between Oxygen extraction ratio(ERO2) and prognosis of septic shock patients in the early stage of resuscitation. Methods The data of the patients with septic shock admitted to the department of Critical Care Medicine of Peking Union Medical College Hospital from January 2016 to July 2021 were retrospectively collected. The patients were divided into the survival group and the death group according to the prognosis of the ICU. The baseline data, and Oxygen metabolism indexes including Oxygen delivery (DO2), Oxygen consumption(VO2), ERO2 and lactate(Lac) of the two groups were collected. Risk factors for ICU death in patients with septic shock were analyzed using multifactorial Logistic regression, and the predictive value of each indicator for ICU death in patients with septic shock was assessed using receiver operating characteristic (ROC) curves. Results A total of 73 patients with septic shock who met the inclusion and exclusion criteria were enrolled, including 21 cases in the death group and 52 cases in the survival group. The differences in acute physiology and chronic health evaluationⅡ(APACHEⅡ) scores and sequential organ failure assessment (SOFA) scores between the two groups were statistically significant (all P < 0.05). Compared with the survival group, 6 h after resuscitation in the death group, Lac [5.6(4.2, 10.0)mmol/L vs. 3.4(2.1, 6.9)mmol/L, P=0.009], VO2[(165±95) mL/(min·m2) vs. (106±58)mL/(min·m2), P=0.012], ERO2[(56.56±19.48)% vs.(33.71±13.24)%, P=0.000] were elevated, and there was no significant difference in DO2 between the two groups[266 (214, 384) mL/(min·m2) vs. 300 (250, 396)mL/(min·m2), P=0.159]. The results of multifactorial Logistic regression analysis showed that ERO2 was an independent risk factor for ICU death in patients with septic shock (OR=1.126, 95% CI: 1.053-1.203, P=0.000). The ROC curve showed that the area under the curve (AUC) of ERO2 for predicting ICU death in septic shock patients was 0.833, with an optimal threshold of 45.93%, sensitivity of 76.19%, specificity of 94.23%, and its predictive efficacy was superior to that of the APACHEⅡ scores(AUC: 0.704), SOFA score(AUC: 0.778), and Lac(AUC: 0.668). Conclusion ERO2 in the early stage of septic shock resuscitation is an independent risk factor for ICU prognosis, which has a good predictive value for the prognosis of septic shock.

Abstract 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 (P treat

The article focuses on the limitations of using Near-Infrared Spectroscopy (NIRS) for assessing convective and diffusive components of oxygen transport during maximum exercise. Topics include the application of the Wagner diagram to understand oxygen transport, the challenges in implementing NIRS for quantifying convective and diffusive processes, and a comparison of invasively measured data with NIRS data in mitochondrial myopathy patients.

Introduction. Ischemic stroke (IS) is a leading cause of disability and mortality worldwide. Several studies have demonstrated the involvement of microRNAs (miRNAs) in brain diseases. miRNA-192-5p is a regulatory molecule in neurodegenerative diseases and its expression was found to be significantly downregulated in the whole blood samples of IS patients, but the specific role of miRNA-192-5p in IS not fully understood. Here, we investigated the role of miRNA-192-5p in a murine model of acute cerebral injury after IS. Material and methods. Male C57BL/6J mice received an intracerebroventricular (i.c.v.) injection of agomir-192-5p or antagomir-192-5p 2 h before middle cerebral artery occlusion (MCAO). Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Brain slices were subjected to Fluoro-Jade B, TUNEL, and immunofluorescence stainings. Contents of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured using enzyme-linked immunosorbent assay (ELISA) kits. In vitro, murine microglial BV-2 cells were subjected to oxygen-glucose deprivation (OGD), and the contents of pro-inflammatory cytokines were measured in cell lysates. Results. miRNA-192-5p was downregulated in the ischemic penumbra of the cerebral cortex. Pretreatment with agomir-192-5p attenuated neurological deficits and reduced cerebral edema and infarct volume in MCAO mice. Agomir-192-5p-treated animals had fewer degenerating and apoptotic neurons in the ischemic penumbra. Additionally, agomir-192-5p significantly suppressed neuroinflammation as evidenced by decreased immunostaining for GFAP and Ibal and decreased levels of pro-inflammatory cytokines. Antagomir-192-5p pretreatment showed the opposite effect. Furthermore, dual specificity tyrosine phosphorylation regulated kinase 1A (Dyrkla) was identified as a target gene of miRNA-192-5p, and the elevated Dyrk1a expression in the ischemic penumbra was markedly reduced by agomir-192-5p. Dyrk1a overexpression in BV-2 microglial cells impaired miRNA-192-5p-mediated inhibition of OGD-induced activation of BV-2 microglial cells. Opposite results were obtained using miRNA-192-5p inhibitor and Dyrk1a siRNA. Conclusions. We found that intracerebroventricular administration of miRNA-192-5p before MCAO attenuated acute cerebral injury by suppressing neuronal apoptosis and neuroinflammation in mice, and these protective effects might be mediated by downregulation of Dyrkla. This study would help identify novel therapeutic targets for IS. [ABSTRACT FROM AUTHOR]

High oxygen affinity hemoglobin (HOAH) variants are rare hemoglobinopathies sometimes associated with congenital erythrocytosis. Patients with HOAH are usually asymptomatic and are incidentally discovered when unexplained erythrocytosis is observed in the complete blood count. Here, we report the first patient with hemoglobin (Hb) Ypsilanti from high-altitude Southern Saudi Arabia, who presented with chronic extreme erythrocytosis (polycythemia) with an Hb concentration of 23 g/dL and hematocrit of 70%. The patient lacked any finding suggestive of secondary erythrocytosis, and the evaluation for acquired polycythemia vera was negative. Hb protein analysis and genetic testing confirmed the presence of a high-affinity Hb variant. Living at high altitude contributed to the presentation of extreme erythrocytosis. Besides highlighting important clinical and diagnostic characteristics, this case illustrates two important diagnostics caveats: high-affinity Hb can be misdiagnosed as another more common qualitative hemoglobinopathy such as Hb S or Hb D carrier state, and it can interfere with HbA1C analysis. [ABSTRACT FROM AUTHOR]

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 β-protein (Aβ) 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 Aβ and tau phosphorylation, and Aβ 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 Aβ 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.

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. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic acidosis as one of the most common perioperative complications has been associated with increased risks for poor prognosis. Routine monitoring methods include blood gas analysis and electrocardiogram, which are limited by time delay effects. And the existing intravital imaging modalities are difficult to achieve in one step. Here, we present a dual-wavelength photoacoustic imaging approach to overcome this dilemma. The aim of this study was to develop a rapid approach for intensive monitoring of acid–base imbalance and cerebral oxygen metabolism. Procedures: We characterized the cerebrovascular structure by label-free dual-wavelength (532 and 559 nm) photoacoustic microscopy in healthy and diabetic mouse models with metabolic acidosis. Concurrently, we developed a single-vessel analysis method to accurately delineate the differential responses of small vessels and quantify the cerebral oxygenation following experimental alteration of pH. Results: We demonstrated that there was an increasing trend in changes of vascular measurements (density, diameter, and relative hemoglobin concentration) and cerebral microvascular oxygen metabolism with the aggravation of acidosis. Furthermore, we established a clinical nomogram for the diagnosis of disease severity and yielded good discrimination ability with area under the curve of 0.920–0.967 and accuracy of 81.9–93.0%. The nomogram was also validated well in the diabetic mouse model with metabolic acidosis. Conclusions: Our photoacoustic imaging approach has great potential for rapid detection of metabolic acidosis and brain oxygen metabolism, which could potentially be applied as a bedside monitoring method for brain protection and timely treatment of acid–base abnormalities. [ABSTRACT FROM AUTHOR]

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 (H2 17O) 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. [ABSTRACT FROM AUTHOR]

Background: Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS). Methods: Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min. Results: For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397–0.701). When comparing SveO2 and NIRS using a Bland–Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was − 17.28–33.09, with an error of 32.5%. Conclusion: DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304. [ABSTRACT FROM AUTHOR]

Oxygen is both vital and toxic to life. Molecular oxygen is the most used substrate in the human body and is required for several hundred diverse biochemical reactions. The discovery of the PHD-HIF-pVHL system revolutionized our fundamental understanding of oxygen sensing and cellular adaptations to hypoxia. It deepened our knowledge of the biochemical underpinnings of numerous diseases, ranging from anemia to cancer. Cellular dysfunction and tissue pathology can result from a mismatch of oxygen supply and demand. Recent work has shown that mitochondrial disease models display tissue hyperoxia and that disease pathology can be reversed by normalization of excess oxygen, suggesting that certain disease states can potentially be treated by modulating oxygen levels. In this review, we describe cellular and organismal mechanisms of oxygen sensing and adaptation. We provide a revitalized framework for understanding pathologies of too little or too much oxygen.

Background: Taohong Siwu Decoction (THSWD) is a widely used traditional Chinese medicine (TCM) prescription in the treatment of ischemic stroke. There are thousands of chemical components in THSWD. However, the key functional components are still poorly understood. This study aimed to construct a mathematical model for screening of active ingredients in TCM prescriptions and apply it to THSWD on ischemic stroke. Methods: Botanical drugs and compounds in THSWD were acquired from multiple public TCM databases. All compounds were initially screened by ADMET properties. SEA, HitPick, and Swiss Target Prediction were used for target prediction of the filtered compounds. Ischemic stroke pathological genes were acquired from the DisGeNet database. The compound–target–pathogenic gene (C-T-P) network of THSWD was constructed and then optimized using the multiobjective optimization (MOO) algorithm. We calculated the cumulative target coverage score of each compound and screened the top compounds with 90% coverage. Finally, verification of the neuroprotective effect of these compounds was performed with the oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The optimized C-T-P network contains 167 compounds, 1,467 predicted targets, and 1,758 stroke pathological genes. And the MOO model showed better optimization performance than the degree model, closeness model, and betweenness model. Then, we calculated the cumulative target coverage score of the above compounds, and the cumulative effect of 39 compounds on pathogenic genes reached 90% of all compounds. Furthermore, the experimental results showed that decanoic acid, butylphthalide, chrysophanol, and sinapic acid significantly increased cell viability. Finally, the docking results showed the binding modes of these four compounds and their target proteins. Conclusion: This study provides a methodological reference for the screening of potential therapeutic compounds of TCM. In addition, decanoic acid and sinapic acid screened from THSWD were found having potential neuroprotective effects first and verified with cell experiments, however, further in vitro and in vivo studies are needed to explore the precise mechanisms involved. [ABSTRACT FROM AUTHOR]

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.

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.

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.

Background: Uncontrolled mitosis of cancer cells and resistance cells to chemotherapy drugs are the challenges of prostate cancer. Thalicthuberine causes a mitotic arrest and a reduction of the effects of drug resistance, resulting in cell death. In this study, we applied bioinformatics and computational biology methods to identify functional pathways and side effects in response to Thalicthuberine in prostate cancer patients. Methods: Microarray data were retrieved from Gene Expression Omnibus (GEO), and protein-protein interactions and gene regulatory networks were constructed, using the Cytoscape software. The critical genes and molecular mechanisms in response to Thalicthuberine and its side effects were identified, using the Cytoscape software and WebGestalt server, respectively. Finally, GEPIA2 was used to predict the relationship between critical genes and prostate cancer. Results: The POLQ, EGR1, CDKN1A, FOS, MDM2, CDC20, CCNB1, and CCNB2 were identified as critical genes in response to this drug. The functional mechanisms of Thalicthuberine include a response to oxygen levels, toxic substances and immobilization stress, cell cycle regulation, regeneration, the p53 signaling pathway, the action of the parathyroid hormone, and the FoxO signaling pathway. Besides, the drug has side effects including muscle cramping, abdominal pains, paresthesia, and metabolic diseases. Conclusion: Our model suggested newly predicted crucial genes, molecular mechanisms, and possible side effects of this drug. However, further studies are required. [ABSTRACT FROM AUTHOR]

The vitreous body, the largest intraocular component, plays a key role in eye development, refraction, cell barrier function, oxygen metabolism and the pathogenesis of assorted diseases. Age, refraction and systemic diseases can cause vitreous metabolic abnormalities. With the continuous development of vitrectomy techniques and equipment, vitreous injections and vitrectomies have increased over the recent decades. However, the normal oxygen tension gradient in the vitreous helps to protect the lens and anterior chamber angle from oxidative stress damage, whereas the increased vitreous oxygen tension around lens and the trabecular meshwork after vitrectomy. It may lead to postoperative nuclear cataract and increase the risk for glaucoma. As a conventional procedure, scleral buckling holds several advantages over vitrectomy in selected cases. This review raises concerns regarding the function of the vitreous and encourages conducting vitreous interventions prudently if it is possible.

Ginseng (Panax ginseng C. A. Mey) is a common traditional Chinese medicine used for anti-inflammation, anti-apoptosis, anti-oxidative stress, and neuroprotection. Ginsenosides Rg1, the main active components isolated from ginseng, may be a feasible therapy for spinal cord injury (SCI). SCI causes endothelial cell death and blood vessel rupture, ultimately resulting in long-term neurological impairment. As a result, encouraging spinal angiogenesis may be a feasible therapy for SCI. This investigation aimed to validate the capacity of ginsenoside Rg1 in stimulating angiogenesis within the spinal cord. Rats with SCI were injected intraperitoneally with ginsenoside Rg1. The effectiveness of ginsenoside Rg1 was assessed using the motor function score and the motor-evoked potential (MEP). Immunofluorescence techniques were applied to identify the spinal cord's angiogenesis. Angiogenic factors were examined through Western Blot (WB) and Immunohistochemistry. Oxygen-glucose deprivation (OGD) was employed to establish the hypoxia-ischemia model in vitro, and astrocytes (As) were given ginsenoside Rg1 and co-cultured with spinal cord microvascular endothelial cells (SCMECs). Immunofluorescence, wound healing test, and tube formation assay were used to identify the co-cultured SCMECs' activity. Finally, network pharmacology analysis and siRNA transfection were applied to verify the mechanism of ginsenoside Rg1 promoting angiogenesis. The rats with SCI treated with ginsenoside Rg1 indicated more significant functional recovery, more pronounced angiogenesis, and higher levels of angiogenic factor expression. In vitro, the co-culture system with ginsenoside Rg1 intervention improved SCMECs' capacity for proliferating, migrating, and forming tubes, possibly by promoting the expression of vascular endothelial growth factor (VEGF) in As via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Ginsenoside Rg1 can regulate As to promote angiogenesis, which may help to understand the mechanism of promoting SCI recovery. Schematic illustration of the role of ginsenoside Rg1 in promoting angiogenesis during spinal cord injury. Ginsenoside Rg1 modulates the activity of astrocytes, promoting the secretion of VEGF via the JAK2/STAT3 pathway. This up-regulated expression of VEGF by astrocytes has a subsequent effect on spinal microvascular endothelial cells, leading to enhanced proliferation, migration, and tubulation of these cells, ultimately contributing to angiogenesis in spinal cord injury. [Display omitted] • Ginsenoside Rg1 can be used as a potential therapeutic agent for effective treatment of spinal cord injury. • Ginsenoside Rg1 regulates astrocytes to promote angiogenesis in spinal cord injury. • JAK2-STAT3 is a key signaling pathway for angiogenesis in spinal cord injury. [ABSTRACT FROM AUTHOR]

BackgroudOxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer.MethodsGene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer.ResultsA total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including LRT2, ATP6V0E2, ODC1, SEL1L3 and VDR was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways.ConclusionsWe developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer

Land salinization is a major form of land degradation, which is not conducive to the growth and quality of fruits and vegetables. Plant salt tolerance can be enhanced by arbuscular mycorrhizal fungi (AMF) or plant growth-promoting rhizobacteria (PGPR). This study examined the effects of inoculation with PGPR singly or in combination with AMF, on the growth and quality of tomato fruits under low saline conditions. Tomatoes were cultivated in a greenhouse with sterilized soil, inoculated with PGPR, AMF, or co-inoculated with PGPR and AMF, and NaCl solution (1%) was added to the soil. The results indicated that AMF + PGPR decreased the roots and shoot biomass accumulation, and increased the number and fresh biomass in tomato fruits to a certain extent compared with non-inoculated plants. PGPR and AMF mediated the level of reactive oxygen and lipid peroxidation, the accumulation of antioxidants, and the activity of antioxidant enzymes, including proanthocyanidins, flavonoids, ascorbic acid, superoxide dismutase, peroxidase, and total antioxidant capacity. Furthermore, PGPR, AMF, and PGPR + AMF improved the overall osmotic adjustments and accumulation of soluble sugars and soluble proteins. Therefore, the AMF-Funneliformis mosseae and PGPR-Bacillus subtilis can potentially alleviate the adverse effects of salt stress and be applied as a biofertilizer in agricultural practice. [ABSTRACT FROM AUTHOR]

Proangiogenic treatment is a potential treatment for acute myocardial infarction (AMI). Morroniside was previously discovered to increase post-AMI angiogenesis in rats as well as the proliferation of rat coronary artery endothelial cells (RCAECs). However, the effects of morroniside on other endothelial cell (EC) functions and underlying mechanisms are unknown. To further clarify the vascular biological activity of morroniside, this work focused on investigating how morroniside influenced endothelial cell functions, such as cell viability, tube formation capacity, migration, and adhesion, and to explore the signaling pathway. Oxygen-glucose deprivation causes ischemic damage in RCAECs (OGD). In vitro investigations were carried out to explore the involvement of morroniside in EC function and pathways mediated by ephrinB. The results revealed that the number of BrdU+ cells and cell viability in the high-dose group were considerably greater than in the OGD group (P < 0.05). The ability of tube formation evaluated by total tube length, tube-like structural junction, and tube area was significantly higher in the morroniside group than in the OGD group (P < 0.001). Morroniside considerably improved migration and adhesion abilities compared to OGD group (P < 0.05 , P < 0.01 , P < 0.001). The protein expression levels of the ephrinB reverse signaling pathway were substantially greater in the morroniside group than in the OGD group (P < 0.05 , P < 0.01). In conclusion, the current study demonstrated that morroniside modulates endothelial cell function via ephrinB reverse signaling pathways and provided a novel insight and therapeutic strategy into vascular biology. [ABSTRACT FROM AUTHOR]

The aim of this cross-sectional study was to assess retinal oxygen metabolism in patients with type 2 diabetes and different stages of nonproliferative diabetic retinopathy (DR) (n = 67) compared with healthy control subjects (n = 20). Thirty-four patients had no DR, 15 had mild DR, and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of a retinal vessel analyzer. Total retinal blood flow (TRBF) was measured using a custom-built Doppler optical coherence tomography system. Retinal oxygen extraction was calculated from retinal oxygen saturation and TRBF. Arteriovenous difference in oxygen saturation was highest in healthy subjects (34.9 ± 7.5%), followed by patients with no DR (32.5 ± 6.3%) and moderate to severe DR (30.3 ± 6.5%). The lowest values were found in patients with mild DR (27.3 ± 8.0%, P = 0.010 vs. healthy subjects). TRBF tended to be higher in patients with no DR (40.1 ± 9.2 μL/min) and mild DR (41.8 ± 15.0 μL/min) than in healthy subjects (37.2 ± 5.7 μL/min) and patients with moderate to severe DR (34.6 ± 10.4 μL/min). Retinal oxygen extraction was the highest in healthy subjects (2.24 ± 0.57 μL O2/min), followed by patients with no DR (2.14 ± 0.6 μL O2/min), mild DR (1.90 ± 0.77 μL O2/min), and moderate to severe DR (1.78 ± 0.57 μL O2/min, P = 0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type 2 diabetes. Furthermore, retinal oxygen extraction decreases with increasing severity of DR. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulse oximetry is the mainstay of patient oxygen monitoring. Measurement error from pulse oximetry is more common for those with darker skin pigmentation, yet this topic remains understudied, and evidence-based clinical mitigation strategies do not currently exist. Our objectives were to measure the rate of occult hypoxemia, defined as arterial oxygen saturation (SaO2) < 88% when pulse oximeter oxygen saturation was between 92-96%, in a racially diverse critically ill population; to analyze degree, direction, and consistency of measurement error; and to develop a mitigation strategy that minimizes occult hypoxemia in advance of technological advancements. METHODS: We performed a multi-center retrospective cohort study of critically ill subjects. RESULTS: Among 105,467 paired observations from 7,693 subjects, we found occult hypoxemia was more common among minority subjects. The frequency of occult hypoxemia was 7.9% versus 2.9% between Black and white subjects, respectively, (P < .001). Pulse oximeter measurement errors were inconsistent throughout a patient encounter, with 67% of encounters having a range of intra-subject measurement errors > 4 percentage points. In 75% of encounters, the intra-subject errors were bidirectional. SaO2 < 88% was less common at higher pulse oximeter oxygenation ranges (4.1% and 1.8% of observations among Black and white subjects at a pulse oximeter threshold of 94-98%). Although occult hypoxemia was further reduced at oxygenation saturation range 95-100%, the frequency of hyperoxemia (partial pressure of arterial oxygen > 110 mm Hg) became more common, occurring in 42.3% of Black and 46.0% of white observations. CONCLUSIONS: Measurement error in pulse oximetry is common for all racial groups, but occult hypoxemia occurred most commonly in Black subjects. The highly variable magnitude and direction of measurement error preclude an individualized mitigation approach. In advance of technological advancements, we recommend targeting a pulse oximetry saturation goal of 94-98% for all patients. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) and brain metastasis (BM) are the most frequent types of brain tumors in adults. Their therapeutic management is quite different and a quick and reliable initial characterization has a significant impact on clinical outcomes. However, the differentiation of GB and BM remains a major challenge in today's clinical neurooncology due to their very similar appearance in conventional magnetic resonance imaging (MRI). Novel metabolic neuroimaging has proven useful for improving diagnostic performance but requires artificial intelligence for implementation in clinical routines. Here; we investigated whether the combination of radiomic features from MR-based oxygen metabolism ("oxygen metabolic radiomics") and deep convolutional neural networks (CNNs) can support reliably pre-therapeutic differentiation of GB and BM in a clinical setting. A self-developed one-dimensional CNN combined with radiomic features from the cerebral metabolic rate of oxygen (CMRO2) was clearly superior to human reading in all parameters for classification performance. The radiomic features for tissue oxygen saturation (mitoPO2; i.e., tissue hypoxia) also showed better diagnostic performance compared to the radiologists. Interestingly, both the mean and median values for quantitative CMRO2 and mitoPO2 values did not differ significantly between GB and BM. This demonstrates that the combination of radiomic features and DL algorithms is more efficient for class differentiation than the comparison of mean or median values. Oxygen metabolic radiomics and deep neural networks provide insights into brain tumor phenotype that may have important diagnostic implications and helpful in clinical routine diagnosis. [ABSTRACT FROM AUTHOR]