Altered Energy Research Articles

Worse glycemic control is associated with an impaired arterial energy transfer pattern in elderly with diabetes

Abstract Background Worse glycaemic control is known to exacerbate endothelial insult, increasing macro- and microvascular complication risks in diabetes. Impaired intracranial haemodynamics have been frequently reported in patients with diabetes alongside with malperfusion causing structural abnormalities, and poor cognitive and cortical functionality (1-2).Assessment of the alterations in energy transfer characteristics derived from hemodynamic signals may provide novel mechanistic information about how worse glycaemic control may affect cerebrovascular perfusion. Wave reflection index(WRI) is a previously proposed measure of arterial energy transfer efficiency which reflects distal impedance mismatch(3-4). Purpose We aim to interrogate potential relationship between a worse glycaemic control and a less efficient arterial energy transfer, which could enhance our understanding of the cerebrovascular-cortical functional coupling on a mechanistic basis in elderly with diabetes. Methods Left middle cerebral artery wave intensity (WI) was computed with arterial blood pressure and flow velocity (transcranial Doppler) signal as previously described (WI = (dP/dt)*(dU/dt)) (Figure 1). Standard statistical tests were used to interrogate the relationship between glycated haemoglobin levels (HbA1c) and WI parameters. Results In 36 patients with diabetes mellitus type-2 (DM2) (mean age = 65.7 ± 8.8 years), backward compression wave intensity (BCWI) and wave reflection ratio (WRI= BCWI/FCWI) were significantly correlated with HbA1c levels before (rBCWI: 0.409 pBCWI:0.013; rWRI:0.345 pWRI:0.040) and after (rBCWI: 0.410 pBCWI:0.018, rWRI:0.351 pWRI:0.045) adjusting for age, sex and mean arterial pressure (Figure 2). Conclusion(s) In elderly patient with DM2, higher HbA1c values indicating worse glycaemic control are significantly correlated with altered cerebrovascular energy transfer characteristics as assessed by MCA wave intensity analysis. Continuous relationship between worse glycaemic control and higher wave reflection index (a measure of less efficient energy transfer in arterial system and distal impedance mismatch) may imply that the use of energy transfer related indices alongside with conventional hemodynamic indices may help providing a more comprehensive pathophysiological understanding about how cardiovascular risk factors interfere with perfusion.Computation of Wave IntensityMain Results

Chronic Starvation-Induced Alterations in Biochemical Parameters and Hypothalamic-Pituitary-Testicular Axis in the Mozambique Tilapia Oreochromis mossambicus (Cichlidae)

Although fish are often exposed to food restrictions in natural or aquafarming conditions, the relationship between altered energy status and the reproduction is not well understood. The aim of the present investigation was to elucidate the effect of chronic food-deprivation on energy status and reproductive axis in male Mozambique tilapia Oreochromis mossambicus. The controls received food ad libitum, whereas the fish in the starvation group were deprived of food for 21 days. The liver showed significantly higher levels of gluconeogenesis and triglycerides, whereas the levels of blood glucose and total protein content in the liver were significantly lower in starved fish compared to controls. Furthermore, the mean numbers of different spermatogenic cells, such as spermatogonia-A, primary spermatocytes, secondary spermatocytes, early spermatids, and late spermatids were significantly lower, but the number of spermatogonia-B did not show a significant difference compared to controls. In starved fish, there was a significant increase in germ cell apoptosis at different stages of development concomitant with faintly immunoreactive androgen receptors in the Sertoli cells of the testis compared with controls. In addition, the percent areas of gonadotropin-releasing hormone—immunoreactive fibres and luteinizing hormone—immunoreactive content—in the proximal pars distalis part of the pituitary gland were significantly lower in starved fish compared with controls. Collectively, these results suggest that decreased energy status negatively affects the gonadotropin-releasing hormone—luteinizing hormone – testicular axis, leading to inhibition of spermatogenesis before entry of germ cells into meiosis through increased apoptosis and decreased expression of androgen receptors in the testis of the Mozambique tilapia.

Unloading-Induced Skeletal Interoception Alters Hypothalamic Signaling to Promote Bone Loss and Fat Metabolism.

Microgravity is the primary factor that affects human physiology in spaceflight, particularly bone loss and disturbances of the central nervous system. However, little is known about the cellular and molecular mechanisms of these effects. Here, it is reported that in mice hindlimb unloading stimulates expression of neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the hypothalamus, resulting in bone loss and altered fat metabolism. Enhanced expression of TH and NPY in the hypothalamus occurs downstream of a reduced prostaglandin E2 (PGE2)-mediated ascending interoceptive signaling of the skeletal interoception. Sympathetic antagonist propranolol or deletion of Adrb2 in osteocytes rescue bone loss in the unloading model. Moreover, depletion of TH+ sympathetic nerves or inhibition of norepinephrine release ameliorated bone resorption. Stereotactic inhibition of NPY expression in the hypothalamic neurons reduces the food intake with altered energy expenditure with a limited effect on bone, indicating hypothalamic neuroendocrine factor NPY in the facilitation of bone formation by sympathetic TH activity. These findings suggest that reduced PGE2-mediated interoceptive signaling in response to microgravity or unloading has impacts on the skeletal and central nervous systems that are reciprocally regulated.

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_17_CJN0000000000000318.mp3.

Seasonal patterns of carbon and water flux responses to precipitation and solar radiation variability in a subtropical evergreen forest, South China

Precipitation and energy are vital factors profoundly affecting carbon and water fluxes in subtropical forest ecosystems. However, knowledge of the seasonality of ecosystem productivity and water fluxes and their dominant controlling factors remains understudied. Based on 12 years (2003–2014) of eddy-covariance measurements, we examined how the seasonal carbon flux components and evapotranspiration respond to climatic variability in a subtropical forest ecosystem. Our results showed that both the magnitude and the percentage of gross ecosystem productivity (GEP) and ecosystem respiration (Reco) in winter increased. The enhanced GEP during winter and dampened Reco in summer and autumn were not sufficient to compensate for the decreased GEP in spring, summer and autumn, and simultaneously increased Reco in spring and winter. Thus, net ecosystem productivity (NEP) slightly diminished during the study period, and the majority of annual net carbon gains occurred in winter and spring with high water use efficiency. In addition, solar radiation predominantly contributed to GEP in spring and winter, while soil moisture is the main contributor in summer. ET greatly determined the GEP in autumn due to both were well-coupled. The vapor pressure deficit (VPD) was a major driver of Reco in summer and autumn inferred that Reco largely depends on substrate availability. However, Reco was mainly attributed to the soil environmental conditions (moisture and temperature) in spring and winter. Our results highlighted that the different extents and asynchronous responses of ecosystem carbon assimilation and respiration to altered energy and moisture availability determined the seasonal patterns of carbon and water fluxes, thus having important implications for assessing or projecting subtropical forest ecosystem responses to current climate change.

Bioenergetic Effects of Polycyclic Aromatic Hydrocarbon Resistance Manifest Later in Life in Offspring of Fundulus heteroclitus from the Elizabeth River.

Shifts in key physiological processes can confer resistance to chemical pollutants. However, these adaptations may come with certain trade-offs, such as altered energy metabolic processes, as evident in Atlantic killifish (Fundulus heteroclitus) in Virginia's Elizabeth River (ER) that have evolved resistance to polycyclic aromatic hydrocarbons (PAHs). We seek to understand the bioenergetic costs of PAH resistance among subpopulations of Atlantic killifish with differing contamination levels in order to examine how these changes manifest across multiple life stages and how these costs might be exacerbated by additional stressors. Bioenergetics data revealed differences in metabolic rates between offspring of PAH-resistant fish and reference fish were absent or minimal in both the embryo and larval stages but pronounced at the juvenile life stage, suggesting that bioenergetic changes in pollution-adapted killifish manifest later in life. We also provide evidence that killifish from remediated sites are more sensitive to PAH exposure than killifish from nonremediated sites, suggesting loss of PAH tolerance following relaxed selection. Collectively, our data suggest that the fitness consequences associated with evolved resistance to anthropogenic stressors may manifest differently over time and depend on the magnitude of the selection pressure. This information can be valuable in effective risk and remediation assessments as well as in broadening our understanding of species responses to environmental change.

Sex-specific effects of acute chlordane exposure in the context of steatotic liver disease, energy metabolism and endocrine disruption.

Chlordane is an organochlorine pesticide (OCP) that is environmentally persistent. Although exposures to OCPs including chlordane have been associated with elevated liver enzymes, current knowledge on OCPs' contribution to toxicant-associated steatotic liver disease (TASLD) and underlying sex-specific metabolic/endocrine disruption are still widely limited. Therefore, the objective of this study was to investigate the sex-dependent effects of chlordane in the context of TASLD. Age-matched male and female C57BL/6 mice were exposed to chlordane (20mg/kg, one-time oral gavage) for two weeks. Female mice generally exhibited lower bodyfat content but more steatosis and hepatic lipid levels, consistent with increased hepatic mRNA levels of genes involved in lipid synthesis and uptake. Surprisingly, chlordane-exposed females demonstrated lower hepatic cholesterol levels. With regards to metabolic disruption, chlordane exposure decreased expression of genes involved in glycogen and glucose metabolism (Pklr, Gck), while chlordane-exposed females also exhibited decreased gene expression of HNF4A, an important regulator of liver identity and function. In terms of endocrine endpoints, chlordane augmented plasma testosterone levels in males. Furthermore, chlordane activated hepatic xenobiotic receptors, including the constitutive androstane receptor, in a sex-dependent manner. Overall, chlordane exposure led to altered hepatic energy metabolism, and potential chlordane-sex interactions regulated metabolic/endocrine disruption and receptor activation outcomes.

Altered Brain Energy Metabolism Related to Astrocytes in Alzheimer's Disease.

Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism. Astrocytes are primarily considered glycolytic cells, suggesting a preference for lactate production. This study aimed to examine alterations in astrocytic activities and their association with brain lactate levels in AD. The study included 30 AD and 30 cognitively unimpaired participants. For AD participants, amyloid and tau depositions were confirmed by positron emission tomography using [11 C]PiB and [18 F]florzolotau, respectively. Myo-inositol, an astroglial marker, and lactate in the posterior cingulate cortex were quantified by magnetic resonance spectroscopy. These magnetic resonance spectroscopy metabolites were compared with plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker, and amyloid and tau positron emission tomography. Myo-inositol and lactate levels were higher in AD patients than in cognitively unimpaired participants (p < 0.05). Myo-inositol levels correlated with lactate levels (r = 0.272, p = 0.047). Myo-inositol and lactate levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores (p < 0.05). Significant correlations were noted between myo-inositol levels and plasma glial fibrillary acidic protein, tau phosphorylated at threonine 181 levels, and amyloid and tau positron emission tomography accumulation in the posterior cingulate cortex (p < 0.05). We found high myo-inositol levels accompanied by increased lactate levels in the posterior cingulate cortex in AD patients, indicating a link between reactive astrocytes and altered brain energy metabolism. Myo-inositol and plasma glial fibrillary acidic protein may reflect similar astrocytic changes as biomarkers of AD. ANN NEUROL 2023.

Stalling the Course of Neurodegenerative Diseases: Could Cyanobacteria Constitute a New Approach toward Therapy?

Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.

Exhaustive exercise alters native and site-specific H2O2 emission in red and white skeletal muscle mitochondria

Mitochondrial reactive oxygen species (ROS) homeostasis is intricately linked to energy conversion reactions and entails regulation of the mechanisms of ROS production and removal. However, there is limited understanding of how energy demand modulates ROS balance. Skeletal muscle experiences a wide range of energy requirements depending on the intensity and duration of exercise and therefore is an excellent model to probe the effect of altered energy demand on mitochondrial ROS production. Because in most fish skeletal muscle exists essentially as pure spatially distinct slow-twitch red oxidative and fast-twitch white glycolytic fibers, it provides a natural system for investigating how functional specialization affects ROS homeostasis. We tested the hypothesis that acute increase in energy demand imposed by exhaustive exercise will increase mitochondrial H2O2 emission to a greater extent in red muscle mitochondria (RMM) compared with white muscle mitochondria (WMM). We found that native H2O2 emission rates varied by up to 6-fold depending on the substrate being oxidized and muscle fiber type, with RMM emitting at higher rates with glutamate-malate and palmitoylcarnitine while WMM emitted at higher rates with succinate and glyceral-3-phosphate. Exhaustive exercise increased the native and site-specific H2O2 emission rates; however, the maximal emission rates depended on the substrate, fiber type and redox site. The H2O2 consumption capacity and activities of individual antioxidant enzymes including the glutathione- and thioredoxin-dependent peroxidases as well as catalase were higher in RMM compared with WMM indicating that the activity of antioxidant defense system does not explain the differences in H2O2 emission rates in RMM and WMM. Overall, our study suggests that substrate selection and oxidation may be the key factors determining the rates of ROS production in RMM and WMM following exhaustive exercise.

Embryonic and juvenile snakes (Natrix maura, Linnaeus 1758) compensate for high elevation hypoxia via shifts in cardiovascular physiology and metabolism.

The colonization of novel environments requires a favorable response to conditions never, or rarely, encountered in recent evolutionary history. For example, populations colonizing upslope habitats must cope with lower atmospheric pressure at elevation, and thus reduced oxygen availability. The embryo stage in oviparous organisms is particularly susceptible, given its lack of mobility and limited gas exchange via diffusion through the eggshell and membranes. Especially little is known about responses of Lepidosaurian reptiles to reduced oxygen availability. To test the role of physiological plasticity during early development in response to high elevation hypoxia, we performed a transplant experiment with the viperine snake (Natrix maura, Linnaeus 1758). We maintained gravid females originating from low elevation populations (432 m above sea level [ASL]-normoxia) at both the elevation of origin and high elevation (2877 m ASL-extreme high elevation hypoxia; approximately 72% oxygen availability relative to sea level), then incubated egg clutches at both low and high elevation. Regardless of maternal exposure to hypoxia during gestation, embryos incubated at extreme high elevation exhibited altered developmental trajectories of cardiovascular function and metabolism across the incubation period, including a reduction in late-development egg mass. This physiological response may have contributed to the maintenance of similar incubation duration, hatching success, and hatchling body size compared to embryos incubated at low elevation. Nevertheless, after being maintained in hypoxia, juveniles exhibit reduced carbon dioxide production relative to oxygen consumption, suggesting altered energy pathways compared to juveniles maintained in normoxia. These findings highlight the role of physiological plasticity in maintaining rates of survival and fitness-relevant phenotypes in novel environments.

The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

Effect of high-starch or high-fibre diets on the energy metabolism and physical performance of horses during an 8-week training period.

Large amounts of high-starch concentrates are traditionally fed to horses in training. However, this has been associated with digestive or muscle diseases and behavioural modifications. In parallel, it has been demonstrated that horses fed high-fibre, low-starch diets achieve the same performance over an exercise test as the ones fed high-starch diets. However, whether the same performance level can be maintained over a longer training cycle is still being determined. This study aimed to compare the evolution in physical performance and cardiorespiratory responses of two groups of French Trotters fed either a control high-starch (15.0g dry matter hay/kg body mass/day + 6.6g dry matter oats/kg body mass/day) or a high-fibre diet (75% of oats replaced by dehydrated alfalfa) over an 8-week training period. The horses that entered the trial were untrained for ≥4months and previously fed hay only. Track training with speed monitoring included interval training sessions and 2400m performance tests from week 1 to week 8 (W8). Before (week 0, W0) and after (week 9, W9) the training period, horses performed an incremental continuous exercise test during which cardiorespiratory parameters were measured. Both groups progressed to the same extent regarding physical performance measured during interval training sessions (acceleration: 0.16m.s-2 at W0 and 0.40m.s-2 at W8; p < 0.0001), the 2400m performance test (average speed: 8.88m.s-1 at W0 and 10.55m.s-1 at W8; p < 0.0001), and the incremental continuous exercise test (speed during the fastest stage: 9.57m.s-1 at W0 and 10.53m.s-1 at W9; p = 0.030). Although oxygen consumption increased with training (p = 0.071), it was not influenced by the diet. On the contrary, carbon dioxide production increased in the high-starch group only (high-starch group: 84.0 vs. high-fibre group: 77.7mL.kg-1.min-1 at W9; p = 0.031). The results illustrate that horses in both groups progressed similarly but did not use the same metabolic pathways during exercise. This hypothesis is supported by carbohydrate oxidation, which tended to increase in the high-starch group at W9 but decreased in the high-fibre group (p = 0.061). In conclusion, the substitution of high-starch by high-fibre diets enabled similar performance over an 8-week training period and altered energy metabolism in a way that could be beneficial during high-intensity exercise.

Altered lipid acyl chain length controls energy dissipation in light-harvesting complex II proteoliposomes by hydrophobic mismatch.

In plants, the major light-harvesting antenna complex (LHCII) is vital for both light harvesting and photoprotection in photosystem II. Previously, we proposed that the thylakoid membrane itself could switch LHCII into the photoprotective state, qE, via a process known as hydrophobic mismatch. The decrease in the membrane thickness that followed the formation of ΔpH was a key fact that prompted this idea. To test this, we made proteoliposomes from lipids with altered acyl chain length (ACL). Here, we show that ACL regulates the average chlorophyll fluorescence lifetime of LHCII. For liposomes made of lipids with an ACL of 18 carbons, the lifetime was ∼2ns, like that for the thylakoid membrane. Furthermore, LHCII appears to be quenched in proteoliposomes with an ACL both shorter and longer than 18 carbons. The proteoliposomes made of short ACL lipids display structural heterogeneity revealing two quenched conformations of LHCII, each having characteristic 77K fluorescence spectra. One conformation spectrally resembles isolated LHCII aggregates, whilst the other resembles LHCII immobilized in polyacrylamide gels. Overall, the decrease in the ACL appears to produce quenched conformations of LHCII, which renders plausible the idea that the trigger of qE is the hydrophobic mismatch.

Tuning dual-atom mediator toward high-rate bidirectional polysulfide conversion in Li-S batteries

An emerging practice in the realm of Li-S batteries lies in the employment of single-atom catalysts (SACs) as effective mediators to promote polysulfide conversion, but monometallic SACs affording isolated geometric dispersion and sole electronic configuration limit the catalytic benefits and curtail the cell performance. Here, we propose a class of dual-atom catalytic moieties comprising hetero- or homo-atomic pairs anchored on N-doped graphene (NG) to unlock the liquid–solid redox puzzle of sulfur, readily realizing Li-S full cell under high-rate-charging conditions. As for Fe-Ni-NG, in-depth experimental and theoretical analysis reveal that the hetero-atomic orbital coupling leads to altered energy levels, unique electronic structures, and varied Fe oxidation states in comparison with homo-atomic structures (Fe-Fe-NG or Ni-Ni-NG). This would weaken the bonding energy of polysulfide intermediates and thus enable facile electrochemical kinetics to gain rapid liquid-solid Li2S4 ↔ Li2S conversion. Encouragingly, a Li-S battery based on the S@Fe-Ni-NG cathode demonstrates unprecedented fast-charging capability, documenting impressive rate performance (542.7 mA h g−1 at 10.0 C) and favorable cyclic stability (a capacity decay of 0.016% per cycle over 3000 cycles at 10.0 C). This finding offers insights to the rational design and application of dual-atom mediators for Li-S batteries.

Control of Photoswitching Kinetics with Strong Light-Matter Coupling in a Cavity.

Most photochemistry occurs in the regime of weak light-matter coupling, in which a molecule absorbs a photon and then performs photochemistry from its excited state. In the strong coupling regime, enhanced light-matter interactions between an optical field and multiple molecules lead to collective hybrid light-matter states called polaritons. This strong coupling leads to fundamental changes in the nature of the excited states including multi-molecule delocalized excitations, modified potential energy surfaces, and dramatically altered energy levels relative to non-coupled molecules. The effect of strong light-matter coupling on covalent photochemistry has not been well explored. Photoswitches undergo reversible intramolecular photoreactions that can be readily monitored spectroscopically. In this work, we study the effect of strong light-matter coupling on the kinetics of photoswitching within optical cavities. Reproducing prior experiments, photoswitching of spiropyran/merocyanine photoswitches is decelerated in a cavity. Fulgide photoswitches, however, show the opposite effect, with strong coupling accelerating photoswitching. While modified merocyanine switching can be explained by changes in radiative decay rates or the amount of light in the cavity, modified fulgide switching kinetics suggest direct changes to excited-state reaction kinetics.

Adiponectin Modulates Smooth Muscle Cell Morpho-Functional Properties in Murine Gastric Fundus via Sphingosine Kinase 2 Activation.

Adipokines are peptide hormones produced by the adipose tissue involved in several biological functions. Among adipokines, adiponectin (ADPN) has antidiabetic and anti-inflammatory properties. It can also modulate food intake at central and peripheral levels, acting on hypothalamus and facilitating gastric relaxation. ADPN exerts its action interacting with two distinct membrane receptors and triggering some well-defined signaling cascades. The ceramidase activity of ADPN receptor has been reported in many tissues: it converts ceramide into sphingosine. In turn, sphingosine kinase (SK) phosphorylates it into sphingosine-1 phosphate (S1P), a crucial mediator of many cellular processes including contractility. Using a multidisciplinary approach that combined biochemical, electrophysiological and morphological investigations, we explored for the first time the possible role of S1P metabolism in mediating ADPN effects on the murine gastric fundus muscle layer. By using a specific pharmacological inhibitor of SK2, we showed that ADPN affects smooth muscle cell membrane properties and contractile machinery via SK2 activation in gastric fundus, adding a piece of knowledge to the action mechanisms of this hormone. These findings help to identify ADPN and its receptors as new therapeutic targets or as possible prognostic markers for diseases with altered energy balance and for pathologies with fat mass content alterations.

Investigating how the electronic and optical properties of a novel cubic inorganic halide perovskite, Sr3NI3 are affected by strain

Background: Inorganic Perovskite materials have sparked the attention of the solar technology sector due to their remarkable structural, optical, and electrical capabilities. In the realm of efficient LEDs, inorganic perovskites have displayed considerable promise, showcasing various benefits such as exceptional color purity, the ability to adjust emission wavelengths, and cost-effective fabrication methods. Methods: The study extensively investigated the bandgap, density of states, electron charge density, structural properties, dielectric properties, loss function, and absorption coefficient of Sr3NI3 under strain using first-principles density functional theory (DFT). Results: At the Gamma (Γ) point, the unstrained flat structure of Sr3NI3 exhibits a direct band gap of 0.733 eV. Observing the spin-orbital coupling (SOC) effect reduces the bandgap to 0.711 eV in Sr3NI3 perovskite. Compressive strain minimizes the prevalence of the structure's bandgap, whereas tensile strain causes a slight elevation. The optical properties of this material, including the dielectric functions, absorption coefficient, reflectivity, and electron loss function, exhibit its excellent absorption capacity in the visible area because of its band characteristics. Conclusions: The research indicates that as the amount of compressive strain rises, the peak values of the dielectric constant of Sr3NI3 shift towards lower photon energy (redshift); meanwhile, when tensile strain is executed, it displays the behavior of altered photon energy with an increase towards higher energy levels (blueshift). Thus, the potential of utilizing Sr3NI3 perovskite in solar cells for energy production and light management is considered promising.

A Culex quinquefasciatus strain resistant to the binary toxin from Lysinibacillus sphaericus displays altered enzyme activities and energy reserves

BackgroundThe resistance of a Culex quinquefasciatus strain to the binary (Bin) larvicidal toxin from Lysinibacillus sphaericus is due to the lack of expression of the toxin’s receptors, the membrane-bound Cqm1 α-glucosidases. A previous transcriptomic profile of the resistant larvae showed differentially expressed genes coding Cqm1, lipases, proteases and other genes involved in lipid and carbohydrate metabolism. This study aimed to investigate the metabolic features of Bin-resistant individuals by comparing the activity of some enzymes, energy reserves, fertility and fecundity to a susceptible strain.MethodsThe activity of specific enzymes was recorded in midgut samples from resistant and susceptible larvae. The amount of lipids and reducing sugars was determined for larvae and adults from both strains. Additionally, the fecundity and fertility parameters of these strains under control and stress conditions were examined.ResultsEnzyme assays showed that the esterase activities in the midgut of resistant larvae were significantly lower than susceptible ones using acetyl-, butyryl- and heptanoyl-methylumbelliferyl esthers as substrates. The α-glucosidase activity was also reduced in resistant larvae using sucrose and a synthetic substrate. No difference in protease activities as trypsins, chymotrypsins and aminopeptidases was detected between resistant and susceptible larvae. In larval and adult stages, the resistant strain showed an altered profile of energy reserves characterized by significantly reduced levels of lipids and a greater amount of reducing sugars. The fertility and fecundity of females were similar for both strains, indicating that those changes in energy reserves did not affect these reproductive parameters.ConclusionsOur dataset showed that Bin-resistant insects display differential metabolic features co-selected with the phenotype of resistance that can potentially have effects on mosquito fitness, in particular, due to the reduced lipid accumulation.Graphical

Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor Improves Leukocyte Energy Metabolism in Hereditary Hemorrhagic Telangiectasia.

The interplay between hypoxia-inducible factors (HIFs) and transforming growth factor beta (TGF-β) is critical for both inflammation and angiogenesis. In hereditary hemorrhagic telangiectasia (HHT), we have previously observed that impairment of the TGF-β pathway is associated with downregulation of HIF-1α. HIF-1α accumulation is mandatory in situations of altered energy demand, such as during infection or hypoxia, by adjusting cell metabolism. Leukocytes undergo a HIF-1α-dependent switch from aerobic mitochondrial respiration to anaerobic glycolysis (glycolytic switch) after stimulation and during differentiation. We postulate that the decreased HIF-1α accumulation in HHT leads to a clinically observed immunodeficiency in these patients. Examination of HIF-1α and its target genes in freshly isolated peripheral blood mononuclear cells (PBMCs) from HHT patients revealed decreased gene expression and protein levels of HIF-1α and HIF-1α-regulated glycolytic enzymes. Treatment of these cells with the HIF-prolyl hydroxylase inhibitor, Roxadustat, rescued their ability to accumulate HIF-1α protein. Functional analysis of metabolic flux using a Seahorse FX extracellular flux analyzer showed that the extracellular acidification rate (indicator of glycolytic turnover) after Roxadustat treatment was comparable to non-HHT controls, while oxygen consumption (indicator of mitochondrial respiration) was slightly reduced. HIF stabilization may be a potential therapeutic target in HHT patients suffering from infections.