Increase In Oxygen Consumption Research Articles

Experimental Study on Constructing a Classification and Early Warning Index System for Non-Stick Coal Spontaneous Combustion

ABSTRACT Focused on the complex underground environment and the difficulty in quantitative characterization of CSC indicator gases, the temperature-programmed experiments were conducted to explore the releasing rule of gaseous compounds during the low-temperature oxidation process of nonstick coal, taking into account coal particle size and mine ventilation volume. By combining the rate of increase in oxygen consumption, the critical temperature for the coal was determined to be 60–80°C, and the dry cracking temperature ranging from 110°C to 120°C. The experimental process revealed that both particle size and ventilation volume have a significant impact on gaseous compounds. Therefore, the coefficient of variation method, gray relational analysis, and weighted gray relational analysis were introduced to evaluate the gas indexes of each temperature range by particle size and air volume. It was found that at 30–50°C, the O2/CH4 ratio was the primary indicator; at 60–80°C, the CO/O2 was selected as the primary index; at 110–120°C, the CO/CO2 and O2/CH4 were selected the primary indicators; and at 130–180°C, the C2H6/CH4 was selected the primary indicator. And build a graded early warning system for coal spontaneous combustion. This study provides a reference for the construction of grading prediction indicators for nonstick coal.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. These cells, which we refer to as Warburg-null cells, maintain wild-type growth rates while producing negligible lactate, show a compensatory increase in oxygen consumption, near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. Warburg-null cells remain amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titres and maintaining product glycosylation. The ability to eliminate lactate production may be useful for biotherapeutic production and provides a tool for investigating a common metabolic phenomenon.

Biomimetic Diselenide-Sonosensitizer Nanoplatform for Enhanced Sonodynamic Therapy and In Situ Remodeling Immunosuppressive Microenvironment via Activating Innate and Adaptive Immunotherapy.

Sonodynamic therapy (SDT), which is non-invasive and controllable has the potential to treat triple-negative breast cancer (TNBC). However, the hypoxia and immunosuppressive tumor microenvironment (TME) often block the production of reactive oxygen species and the induction of SDT-activated immunogenic cell death, thus limiting the activation of adaptive immune responses. To alleviate these challenges, we proposed the development of a multifunctional biomimetic nanoplatform (mTSeIR), which was designed with diselenide-conjugated sonosensitizers and tirapazamine (TPZ), encapsulated within M1 macrophage membrane. This nanoplatform utilized hypoxia-induced chemotherapy to improve the efficacy of SDT, to further enhance adaptive immunotherapy by activating innate immunity and remodeling the immunosuppressive TME. Firstly, the prodrug TPZ was activated due to the increased oxygen consumption associated with SDT. Subsequently, the mTSeIR enhanced repolarization of M2 macrophages to the M1 phenotype. The diselenide component in mTSeIR effectively activated the natural killer cell-mediated antitumor innate immune response. Ultimately, in vivo studies indicated that mTSeIR+US with good biosafety achieved over 98% tumor inhibition and enhanced adaptive immunotherapy. This research presents an efficient approach that addressed the limitations of SDT and achieves simultaneous activation of both innate and adaptive immunotherapy, resulting in significant antitumor and anti-metastatic efficacy in TNBC.

NSD2 mediated H3K36me2 promotes pulmonary arterial hypertension by recruiting FOLR1 and metabolism reprogramming.

Pulmonary artery hypertension (PAH) is characterized by a cancer-like metabolic shift towards aerobic glycolysis. Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone methyltransferase, has been implicated in PAH, yet its precise role remains unclear. In this study, we induced PAH in C57BL/6 mice using monocrotaline (MCT) and observed increased FOLR1 expression in PAH tissues, which was suppressed by NSD2 knockdown. Silencing NSD2 or FOLR1 inhibited the proliferation and migration of pulmonary artery endothelial cells (PAECs) and alleviated PAH phenotypes, right ventricular dysfunction, and pulmonary artery remodeling. Mechanistically, NSD2 knockdown prevented nuclear translocation of FOLR1 and its interaction with H3K36me2. Metabolic analysis revealed that NSD2 or FOLR1 knockdown reversed the increased oxygen consumption rate, extracellular acidification rate, glucose consumption, lactate production, and G6PD activity in MCT-treated PAECs. Furthermore, NSD2 or FOLR1 silencing decreased the expression of key glycolytic genes (HK2, TIGAR, and G6PD) by suppressing their promoter activity and weakening the interaction between FOLR1/H3K36me2 and these gene promoters. Our findings suggest that NSD2-mediated H3K36me2 recruits FOLR1 to promote PAH, and FOLR1 acts as a transcriptional factor to upregulate glycolytic gene expression in PAECs.

Changes in the Phenotype and Metabolism of Peritoneal Macrophages in Mucin-2 Knockout Mice and Partial Restoration of Their Functions In Vitro After L-Fucose Treatment.

In the development of inflammatory bowel disease (IBD), peritoneal macrophages contribute to the resident intestinal macrophage pool. Previous studies have demonstrated that oral administration of L-fucose exerts an immunomodulatory effect and repolarizes the peritoneal macrophages in vivo in mice. In this study, we analyzed the phenotype and metabolic profile of the peritoneal macrophages from Muc2-/- mice, as well as the effect of L-fucose on the metabolic and morphological characteristics of these macrophages in vitro. The investigation utilized flow cytometry, quantitative PCR (qPCR), measurement of the intracellular ATP and Ca2+ concentrations, an analysis of mitochondrial respiration and membrane potential, and transmission electron microscopy (TEM) for ultrastructural evaluations. The Muc2-/- mice exhibited lower intracellular ATP and Ca2+ levels in their peritoneal macrophages, a higher percentage of stellate macrophages, and an increased oxygen consumption rate (OCR), combined with a higher percentage of mitochondria displaying an abnormal ultrastructure. Additionally, there was a five-fold increase in condensed mitochondria compared to their level in C57BL/6 mice. The number of CD209+ peritoneal macrophages was reduced three-fold, while the number of M1-like cells increased two-fold in the Muc2-/- mice. L-fucose treatment enhanced ATP production and reduced the expression of the Parp1, Mt-Nd2, and Mt-Nd6 genes, which may suggest a reduction in pro-inflammatory factor production and a shift in the differentiation of peritoneal macrophages towards the M2 phenotype.

The Effects of Novel Co-Amorphous Naringenin and Fisetin Compounds on a Diet-Induced Obesity Murine Model.

In recent studies, it has been shown that dietary bioactive compounds can produce health benefits; however, it is not known whether an improvement in solubility can enhance their biological effects. Thus, the aim of this work was to study whether co-amorphous (CoA) naringenin or fisetin with enhanced solubility modify glucose and lipid metabolism, thermogenic capacity and gut microbiota in mice fed a high-fat, high-sucrose (HFSD) diet. Mice were fed with an HFSD with or without CoA-naringenin or CoA-fisetin for 3 months. Body weight, food intake, body composition, glucose tolerance, hepatic lipid composition and gut microbiota were assessed. CoA-naringenin demonstrated significant reductions in fat-mass gain, improved cholesterol metabolism, and enhanced glucose tolerance. Mice treated with CoA-naringenin gained 45% less fat mass and exhibited improved hepatic lipid profiles, with significant reductions seen in liver triglycerides and cholesterol. Additionally, both CoA-flavonoids increased oxygen consumption (VO2), contributing to enhanced energy expenditure and improved metabolic flexibility. Thermogenic activation, indicated by increased UCP1 and PGC-1α levels, was observed with CoA-fisetin, supporting its role in fat oxidation and adipocyte size reduction. Further, both CoA-flavonoids modulated gut microbiota, restoring diversity and promoting beneficial bacteria, such as Akkermansia muciniphila, which has been linked to improved metabolic health. These findings suggest that co-amorphous naringenin or fisetin offers promising applications in improving solubility, metabolic health, and thermogenesis, highlighting the potential of both as therapeutic agents against obesity and related disorders.

Cardiorespiratory system of massage therapists when performing a dosed massage procedure

The article tells about the presentation of a number of studies on the effect of massage procedures on the physiological, biochemical and psychological status of a person, while work on evaluating the functional indicators of massage therapists during the procedure is rare. The study aims to determine the functional state of the cardiorespiratory system (CRS) of massage specialists in the dynamics of performing a 30-minute back massage session. The object of the study was 10 male massage therapists (age 36.0 (29.0;42.0); BMI 24.7(23.3;31.3). The study consisted in performing a classical back massage procedure for 30 minutes according to a generally accepted technique using six massage techniques. To determine the functional state during the work of specialists, an ergospirometric system and measurement of blood pressure (BP) by the Korotkiy method were used. During the massage procedure, specialists noted an increase in metabolic parameters, oxygen consumption (OC), respiratory coefficient (RC) and energy consumption, as well as blood pressure by the 30th minute of the procedure. When performing a 30-minute back massage, massage specialists significantly mobilize the links of the cardiorespiratory system. At the end of the procedure, there is an increase in blood pressure. However, the maximum increase in the parameters of the cardiorespiratory system occurs when performing a shock vibration reception. Limitations. Due to the small sample of the group, it is not possible to statistically reliably assess the significance of changes in some indicators. Ethics. The protocol of the experiment corresponded to the Helsinki Declaration. The study was developed and conducted in accordance with the methodological guidelines of the Local Scientific Research Committee on Bioethics of the Institute of Physiology of the Komi Scientific Center of the Ural Branch of the Russian Academy of Sciences.

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY ON STANDARDIZED FENUGREEK SEED EXTRACT COMPOSITION FOR ENDURANCE ENHANCEMENT IN RECREATIONALLY ACTIVE YOUNG SUBJECTS

Objective: To evaluate the efficacy and safety of 8-week supplementation with FEΔE (fenugreek seed extracts composition, standardized to 4-hydroxyisolecuine, trigonelline, and select glycosides) on endurance capacity in recreationally active young male subjects, in a randomized, double-blind, Placebo-controlled manner. Methods: The 153 male participants were randomized equally into three groups and received either 300 mg or 600 mg of FeΔE capsules or a matching Placebo. Each participant performed endurance exercise training four times per week and visited the study center on the day of recruitment (baseline) and end of week-4, and week-8. The efficacy outcome measures were endurance (overall, cardiovascular, respiratory, and metabolic), power, work, physical and central fatigue, and stress, whereas safety outcomes were adverse events monitoring, compliance, and biochemical laboratory measurements. Results: FEΔE supplementation (but not Placebo) showed statistically significant beneficial changes in overall (increased time to exhaustion and total distance run), respiratory (increased oxygen consumption), metabolic (increased metabolic equivalent and decreased non-esterified fatty acids levels), physical fatigue (decreased Wingate fatigue index), central fatigue (reduced visual analog score), and mental endurance (decreased mental domain score in the Multidimensional Fatigue Symptom Inventory-Short Form) during within the group (vs. baseline) comparisons. The safety outcome measures did not differ between the groups (FEΔE vs. Placebo). Conclusion: Eight weeks of FEΔE supplementation in recreationally active participants resulted in comprehensive endurance enhancement, including respiratory, metabolic, and mental endurance. FEΔE supplementation was found to be safe without serious adverse events.

Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment.

High grade serous ovarian cancer displays two metabolic subtypes; a high OXPHOS subtype that shows increased expression of genes encoding electron transport chain components, increased oxygen consumption, and increased chemosensitivity, and a low OXPHOS subtype that exhibits glycolytic metabolism and is more drug resistant. We show here in patient-derived organoids and in the xenografts obtained by their subcutaneous implantation that the low OXPHOS subtype shows higher lactate dehydrogenase activity and monocarboxylate transporter 4 expression than the high OXPHOS subtype and increased lactate labeling in 13C magnetic resonance spectroscopy (MRS) measurements of hyperpolarized [1-13C]pyruvate metabolism. There was no difference between the subtypes in PET measurements of 2-deoxy-2-[fluorine-18]fluoro-D-glucose ([18F]FDG) uptake. Both metabolic imaging techniques could detect the early response to Carboplatin treatment in drug-sensitive high OXPHOS xenografts and no response in drug-resistant in low OXPHOS xenografts. 13C magnetic resonance spectroscopic imaging of hyperpolarized [1-13C]pyruvate metabolism has the potential to be used clinically to distinguish low OXPHOS and high OXPHOS tumor deposits in HGSOC patients and to detect their differential responses to treatment.

Modulation of OPC Mitochondrial Function by Inhibiting USP30 Promotes Their Differentiation.

Multiple lines of evidence indicate that mitochondrial dysfunction occurs in demyelinating diseases, such as multiple sclerosis (MS). Failure of remyelination is thought to be caused in part by a block of oligodendrocyte progenitor cell (OPC) differentiation into oligodendrocytes, which generate myelin sheaths around axons. The process of OPC differentiation requires a substantial amount of energy and high demand for ATP which is supplied through the mitochondria. In this study, we highlight mitochondrial gene expression changes during OPC differentiation in two murine models of remyelination and in human postmortem MS brains. Given these transcriptional alterations, we then investigate whether genetic alteration of USP30, a mitochondrial deubiquitinase, enhances OPC differentiation and myelination. By genetic knockout of USP30, we observe increased OPC differentiation and myelination without affecting OPC proliferation and survival in invitro and exvivo assays. We also find that OPC differentiation is accelerated invivo following focal demyelination in USP30 knockout mice. The promotion of OPC differentiation and myelination observed is associated with increased oxygen consumption rates in USP30 knockout OPCs. Together, these data indicate a role for mitochondrial function and USP30 in OPC differentiation and myelination.

Molybdenum isotopic evidence for linked changes in North Pacific Intermediate Water and subtropical Northwest Pacific redox conditions over the last 200 k.y

Through biological productivity and ocean-atmosphere CO2 exchange, North Pacific mid-depth ventilation has the potential to regulate regional climate over glacial timescales. Nevertheless, the subtropical Northwest Pacific currently lacks continuous long redox records that would enable us to evaluate this process. In this instance, we present δ98/95Mo and redox-sensitive trace element data derived from Okinawa Trough sediments to reconstruct redox conditions and assess their possible significance in regulating atmospheric CO2 in the subtropical Northwest Pacific over the last 200 k.y. Enhanced oxic conditions induced by a strengthened Kuroshio Current during Marine Isotope Stage (MIS) 1 suggest the presence of enhanced deep water ventilation and upwelling in the Okinawa Trough, which likely contributed to high atmospheric CO2 concentrations during interglacial periods. The Okinawa Trough may have been oxic and served as a regional net carbon sink during MIS2 and MIS6, due to glacial North Pacific Intermediate Water (GNPIW) and a weak Kuroshio Current. During interglacials, high productivity brought on by the stronger East Asian Summer Monsoon (EASM) leads to an increase in organic matter burial and oxygen consumption. This substantial positive excursion in δ98/95Mo values during MIS4 and early MIS3 can be linked to the anaerobic oxidation of methane (AOM) and the release of methane-rich fluids from methane hydrate decomposition. Our findings highlight potential links between higher upwelling, GNPIW expansion, and the underlying processes regulating the atmospheric CO2 budget in the subtropical North Pacific during the late Quaternary.

Nuciferine inhibits osteoclast formation through suppressing glycolysis metabolic programming and ROS production.

Nuciferine (NCF) is a bioactive compound from lotus leaves and has been proven to prevent osteoclastogenesis and ovariectomy-induced osteoporosis by our previous research. However, the underlying mechanism is still unclear. In this research, Raw264.7 cells were induced into osteoclast with or without NCF. CCK-8 and Edu assays were performed to detect the effects of 30 μM NCF on cell viability and proliferation. TRAP staining and bone resorption assays were performed to observe the role of NCF in osteoclastogenesis and bone resorption. RT-PCR and Western blot were performed to detect the effects of NCF on osteoclast-related genes, glycolysis-related genes, and reactive oxygen species (ROS)-related genes. Seahorse assays, lactate concentration and glucose consumption were performed to observe cell metabolism change. DCFH-DA fluorescent probe was used to detect ROS level. In this work, 30 μM NCF could not influence cell viability and cell proliferation. Osteoclast differentiation could be inhibited by 30 μM NCF. Bone resorption assay could also observe that bone resorption ability was successfully inhibited by 30 μM NCF. In seahorse assay, we discovered that NCF could decrease extracellular acid rate and increase oxygen consumption. RT-PCR and Western blot results showed that NCF could decrease the expression of hexokinase2, pyruvate kinase muscle 2, and lactate dehydrogenase A and that NCF could also weaken the concentration of lactate. However, pyruvate kinase muscle 2 activator (GC69716) and lactate addition could promote osteoclastogenesis and bone resorption and promote the expression of c-Fos and nuclear factor of activated T cells c1. Besides, NCF could also inhibit the production of ROS. In conclusion, NCF might inhibit osteoclast formation through inhibiting glycolysis metabolism and ROS production.

Bottom water hypoxia enhanced by vertical migration of the raphidophyte Chattonella sp. in the Ariake Sea, Japan

In general, the formation of hypoxic water masses in coastal waters is caused by the restriction of vertical oxygen transport due to enhanced stratification, and the increase in oxygen consumption due to the decomposition of organic matter supplied from phytoplankton blooms. However, the direct relationship between phytoplankton blooms and hypoxia has been rarely reported. In this study, we clarified the relationship between the development of a hypoxic water mass (< 3 mg L−1) and a bloom of the raphidophyte Chattonella sp. in the Ariake Sea, Japan through field surveys and experiments to measure the water oxygen demand. The process of development of and recovery from the hypoxic water mass in a spring-neap tidal cycle was observed. From the spring to the neap tide, high-salinity, high-density water from offshore intruded into the bottom layer of the inner part of the bay, strengthening the stratification and developing a hypoxic water mass. In this period, the bacterial oxygen demand was dominant during the day in the bottom layer. At night, oxygen consumption increased due to the respiration of Chattonella that had accumulated in the bottom layer, reaching five times the amount during the day. In the following spring tides, the stratification weakened and the hypoxic water mass disappeared. However, water oxygen demand was the highest, suggesting the influence of the decay of Chattonella that caused the bloom. These results indicate that the increase in oxygen consumption at night due to the diurnal vertical migration of Chattonella greatly influenced the development of the hypoxic water mass.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p&lt;0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4121527: Empagliflozin Improves Mitochondrial Biogenesis in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by endothelial proliferation and progressive pulmonary vascular (PV) remodeling. Empagliflozin (EMPA), a sodium glucose cotransporter 2 (SGLT2) inhibitor, benefits heart failure patients, potentially mediated by improved mitochondrial function. This study aimed to explore the impact of EMPA in PAH. Methods and Results: Immunohistochemistry of pulmonary arteries revealed the expression of SGLT2 in the intima of PAH patients. Microvascular endothelial cells (MVECs) were isolated from lungs of control subjects (CTRL) and PAH patients and found intense expression of SGLT2 in PAH MVECs. Western blot showed significantly higher expression of SGLT2, while PGC-1α, a transcriptional coactivator known as a master regulator of mitochondrial biogenesis, was lower in PAH MVECs compared to CTRL (Image 1). PAH MVECs were treated with EMPA (1 μM) and observed a significant increase of PGC-1α and BMPR2-pSmad1/5/9. Similarly, knockdown of SGLT2 using siRNA resulted in enhanced expression of PGC-1α. Moreover, Seahorse analysis revealed increased oxygen consumption rate and reduced extracellular acidification rate by EMPA, suggesting that EMPA improved mitochondrial respiration. In addition, EMPA attenuated reactive oxygen species and proliferation of PAH MVECs, as revealed by MitoTracker analysis and MTT assay respectively. For the in vivo study, Sprague-Dawley rats (120-180 gram) were injected with SU5416 (Week-0) and exposed to hypoxia for 3 weeks followed by normoxia. After randomization at Week-4, rats were treated with EMPA (300 mg/kg in chow, n=12) or placebo (PLAC, n=12). Catheterization and histological analysis were performed at Week-8. EMPA decreased PV resistance index (0.21±0.02 vs. 0.37±0.05 mmHg/mL/min/mm 2 , p=0.01), ameliorated intima thickening (21.0±7.5 vs. 40.0±7.8%, p&lt;0.01) and vessel occlusion (Image 2). We further conducted a single-center, open-label, single-arm interventional proof-of-concept study to assess the tolerability of 12 weeks of treatment with 10mg of EMPA as add-on therapy in eight patients with a prior PAH diagnosis. There were no treatment related adverse events during the study time course. Conclusions: EMPA directly improved mitochondrial biogenesis and attenuated proliferation of MVECs from PAH patients and reversed PV remodeling in experimental PAH. EMPA treatment was feasible in patients with PAH. EMPA may serve as a new therapeutic option for PAH.

Seasonal variation of dissolved oxygen in river water in an urbanized area: example of the Vladayska River

This study investigates the seasonal variation of dissolved oxygen (DO) concentrations in urbanized rivers, with a focus on the Vladayska River in Sofia, and examines key influencing factors such as temperature, biological oxygen demand (BOD5), chemical oxygen demand (COD), precipitation and river runoff. The waters of the Vladayska River, subjected to significant anthropogenic pressure, show significant fluctuations in DO levels, with the lowest concentrations recorded in summer and autumn. These periods coincide with high water temperatures, low river discharge, and elevated BOD5 and COD levels, indicating increased oxygen consumption by organic and chemical pollutants. The results show that DO levels in the Vladayska River fall below critical thresholds (5 mg/L) in summer and autumn, representing an ecological risk and reducing river waters’ self-purification capacity. In spring and winter, higher DO levels suggest a seasonal recovery associated with cooler temperatures and increased river flow volume. This study accentuates the seasonal decline in dissolved oxygen levels in urbanized rivers due to both natural processes and intensive anthropogenic activity, highlighting the importance of continuous water quality monitoring.

Metabolic rate and mitochondrial physiology adjustments in Arctic char (Salvelinus alpinus) during cyclic hypoxia.

Diel fluctuations of oxygen levels characterize cyclic hypoxia and pose a significant challenge to wild fish populations. Although recent research has been conducted on the effects of hypoxia and reoxygenation, mechanisms by which fish acclimatize to cyclic hypoxia remain unclear, especially in hypoxia-sensitive species. We hypothesized that acclimation to cyclic hypoxia requires a downregulation of aerobic metabolic rate and an upregulation of mitochondrial respiratory capacities to mitigate constraints on aerobic metabolism and the elevated risk of oxidative stress upon reoxygenation. We exposed Arctic char (Salvelinus alpinus) to 10days of cyclic hypoxia and measured their metabolic rate and mitochondrial physiology to determine how they cope with fluctuating oxygen concentrations. We measured oxygen consumption as a proxy of metabolic rate and observed that Arctic char defend their standard metabolic rate but decrease their routine metabolic rate during hypoxic phases, presumably through the repression of spontaneous swimming activities. At the mitochondrial level, acute cyclic hypoxia increases oxygen consumption without ADP (CI-LEAK) in the liver and heart. Respiration in the presence of ADP (OXPHOS) temporarily increases in the liver and decreases in the heart. Cytochrome c oxidase oxygen affinity also increases at day 3 in the liver. However, no change occurs in the brain, which is likely primarily preserved through preferential perfusion (albeit not measured in this study). Finally, in vivo measurements of reactive oxygen species revealed the absence of an oxidative burst in mitochondria in the cyclic hypoxia group. Our study shows that Arctic char acclimatize to cyclic hypoxia through organ-specific mitochondrial adjustments.

Lactate utilization in Lace1 knockout mice promotes browning of inguinal white adipose tissue

Recent studies have focused on identifying novel genes involved in the browning process of inguinal white adipose tissue (iWAT). In this context, we propose that the mitochondrial ATPase gene lactation elevated 1 (Lace1) utilizes lactate to regulate the browning capacity of iWAT, specifically in response to challenge with CL-316,243 (CL), a beta3-adrenergic receptor (β3-AR) agonist. The mice were injected with CL over a span of 3 days and exposed to cold temperatures (4–6 °C) for 1 week. The results revealed a significant increase in Lace1 expression levels during beige adipogenesis. Additionally, a strong positive correlation was observed between Lace1 and Ucp1 mRNA expression in iWAT under browning stimulation. To further explore this phenomenon, we subjected engineered Lace1 KO mice to CL and cold challenges to validate their browning potential. Surprisingly, Lace1 KO mice presented increased oxygen consumption and heat generation upon CL challenge and cold exposure, along with increased expression of genes related to brown adipogenesis. Notably, deletion of Lace1 led to increased lactate uptake and browning in iWAT under CL challenge compared with those of the controls. These unique phenomena stem from increased lactate release due to the inactivation of pyruvate dehydrogenase (PDH) in the hearts of Lace1 KO mice.

Inhibition of ketohexokinase prevents fructose-induced insulin resistance and endothelial dysfunction in high fat and sucrose-fed mice via enhancing energy expenditure

Abstract Introduction Cardiovascular disease linked to fatty liver poses a significant threat to health. Consumption of high-fat diets (HFD) is known to trigger a cascade of health issues including obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). These conditions are exacerbated, with the addition of dietary sugar to high-fat diets (HFSD), resulting in non-alcoholic steatohepatitis (NASH). Studies have shown that fructokinase (ketohexokinase or KHK) knockdown protects mice from HFSD-induced NASH. Purpose This study focused on examining the temporal changes of metabolic perturbations, triggered by sugar consumption, particularly in the transition from fatty liver to cardiovascular disease. Methods C57/BL6 wild type (WT) and KHK-knockout mice were fed with HFD or HFSD for different durations between 6 to 20 weeks, to induce NAFLD and NASH. Western blotting and quantitative-PCR were carried out on tissues and isolated endothelial cells for protein and mRNA expressions, respectively. Glucose and insulin tolerance tests and whole-body energy measurements were performed at different time-points. Combined Laboratory Animal Monitoring System was used to monitor various parameters of energy expenditure. Functional interactions between endothelial cells and adipose tissues were carried out using an in-house Organ-On-a-chip technology. Endothelial function was studied by measuring isometric tensions in organ bath. Results KHK-deficient mice had significantly lower weight compared to WT littermates. Wild-type mice fed HFD and HFSD exhibited significant glucose intolerance, insulin resistance, and endothelial dysfunction compared to KHK-knockout mice. However, HFSD led to more severe outcomes compared to HFD, demonstrating differing temporal effects on glucose intolerance and insulin resistance. Interestingly, KHK-knockout mice were significantly protected from the effects induced by HFSD, as well as, such as increased body weight, fasting hyperglycemia, hyperinsulinemia and endothelial function. KHK-knockout mice exhibited significant increase in oxygen consumption and energy expenditure, both in HFD and HFSD-fed conditions. These data suggest that high energy-expenditure is one of the primary mechanisms, in reducing adiposity and body weight in HFSD-fed knockout mice. Notably, KHK-deficient mice were protected against sugar-induced fat accumulation, random hyperinsulinemia and significant impairment of endothelial function. Conclusions A novel finding in this study is that KHK ablation protects not only against HFSD-induced, but also HFD-induced pathologies via significantly enhancing energy expenditure. The results suggest that targeting KHK could potentially mitigate the development of fatty liver and cardiovascular diseases, induced by high calorie diets.

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (&amp;gt;3 months) and stable HF, with left ventricular ejection fraction (LVEF) &amp;lt;50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.