Production Rates Of Species Research Articles

Cannula Implantation Reduces the Severity of the Beta Amyloid Effect on Peroxidized Lipids and Glutathione Levels in the Brain of BALB/c Mice

Sporadic Alzheimer’s disease (sAD) is the most common of neurodegenerative disorders. The lack of effective therapy indicates that the mechanisms of sAD development remain poorly understood. To investigate this pathology in animals, intracerebroventricular injection of β-amyloid peptide (Aβ) using a Hamilton syringe, either during stereotactic surgery or through a pre-implanted cannula, is used. In this study, we analyzed the effect of chronic cannula implantation on the severity of Aβ effects at the behavioral, histological, and biochemical levels. The results showed that the local damage to neural tissue caused by cannulation has no bearing on the effect of Aβ on animal behavior and the microglial parameters of the unilateral hippocampus two weeks after the Aβ administration. However, cannula implantation fundamentally modifies some biochemical markers of the oxidative stress that occurs in the brain tissue in response to Aβ administration. Thus, the presence of a cannula reduces the severity of the Aβ impact on the levels of peroxidized lipids and glutathione two- and 10-fold, respectively. It is important to note that the detected changes are chronic and systemic. This is known because the homogenate of the entire contralateral (in relation to the cannula implantation site) hemisphere was analyzed, and the analysis was performed two weeks after implantation. At the same time, cannulation does not affect the rate of reactive oxygen species production. The obtained data indicate that chronic implantation of a cannula into the brain of experimental animals fundamentally distorts some parameters of oxidative stress in the neural tissue, which are widely used to assess the severity of experimental Alzheimer’s-type diseases.

Simulated ischaemia/reperfusion impairs trophoblast function through divergent oxidative stress- and MMP-9-dependent mechanisms.

Early-onset pre-eclampsia is believed to arise from defective placentation in the 1st trimester, leading to placental ischaemia/reperfusion (I/R) and oxidative stress. However, our current understanding of the effects of I/R and oxidative stress on trophoblast function is ambiguous in part due to studies exposing trophoblasts to hypoxia instead of I/R, and which report conflicting results. Here we present a model of simulated ischaemia/reperfusion (SI/R) to recapitulate the pathophysiological events of early-onset PE, by exposing 1st trimester cytotrophoblast HTR-8/SVneo cells to a simulated ischaemia buffer followed by reperfusion. We examined different ischaemia and reperfusion times and observed that 1h ischaemia and 24h reperfusion induced an increase in reactive oxygen species (ROS) production (p < 0.0001) and oxygen consumption rate (p < 0.01). SI/R-exposed trophoblast cells exhibited deficits in migration, proliferation and invasion (p < 0.01). While the deficits in migration and proliferation were rescued by antioxidants, suggesting a ROS-dependent mechanism, the loss of invasion was not affected by antioxidants, which suggests a divergent ROS-independent pathway. In line with this, we observed a decrease in MMP-9, the key regulatory enzyme necessary for trophoblast invasion (p < 0.01), which was similarly unaffected by antioxidants, and pharmacological inhibition of MMP-9 replicated the phenotype of deficient invasion (p < 0.01). Collectively, these data demonstrate that I/R impairs trophoblast migration and proliferation via a ROS-dependent mechanism, and invasion via a ROS-independent loss of MMP-9, disambiguating the role of oxidative stress and providing insights into the response of trophoblasts to I/R in the context of early-onset PE.

Enhancing degradation of sulfamethoxazole by layered double hydroxide/carbon nanotubes catalyst via synergistic effect of photocatalysis/persulfate activation

A Co3Mn-LDHs and carbon nanotube (Co3Mn-LDHs/CNT) composite catalyst was constructed for permonosulfate (PMS) activation and degrading sulfamethoxazole (SMX) under Vis light irradiation. The introduction of CNTs into Co3Mn-LDHs facilitate the exciton dissociation and carrier migration, and the e− and h+ were readily separated from Co3Mn-LDHs/CNT in the photocatalysis process, which promoted the production rate of reactive oxygen species (ROS), so the Co3Mn-LDHs + Vis + PMS system exhibited better activity with an SMX degradation ratio of 61.25% than those of Co3Mn-LDHs + Vis system (42.30%) and Co3Mn-LDHs + PMS system (48.30%). After 10 cycles, the degradation rate of SMX only decreased by 7.16%, indicating the good reusability of the Co3Mn-LDHs/CNTs catalyst. The results of electron paramagnetic resonance (EPR) analysis and radical quenching experiments demonstrated that that the SO4•− played crucial role for SMX removal in Co3Mn-LDHs/CNTs + Vis + PMS system, and both e− and h+ made an important contribution to activating PMS to produce ROS. Overall, this work provided an excellent catalyst for photo-assisted PMS activation and suggested the activation mechanism for organic pollutant remediation.

Anti-inflammatory effect and its mechanism of Saracae Cortex based on zebrafish model and network pharmacology

This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

Ejection and dynamics of aggregates in the coma of comet 67P/Churyumov-Gerasimenko

The process of gas-driven ejection of refractory materials from cometary surfaces continues to pose a challenging question in cometary science. The activity modeling of comet 67P/Churyumov-Gerasimenko, based on data from the Rosetta mission, has significantly enhanced our comprehension of cometary activity. But thermophysical models have difficulties in simultaneously explaining the production rates of various gas species and dust. It has been suggested that different gas species might be responsible for the ejection of refractory material in distinct size ranges. This work focuses on investigating the abundance and the ejection mechanisms of large aggregates (gtrsim 1 cm) from the comet nucleus. We aim to determine their properties and map the distribution of their source regions across the comet surface. This can place constraints on activity models for comets. We examined 189 images acquired at five epochs by the OSIRIS/NAC instrument on board the Rosetta spacecraft. Our goal was to identify bright tracks produced by individual aggregates as they traversed the camera field of view. In parallel, we generated synthetic images based on the output of dynamical simulations involving various types of aggregates. By comparing these synthetic images with the observations, we determined the characteristics of the simulated aggregates that most closely resemble the observations. We have identified over 30000 tracks present in the OSIRIS images, derived constraints on the characteristics of the aggregates, and mapped their origins on the nucleus surface. The aggregates have an average radius of $ cm and a bulk density consistent with that of the comet's nucleus. Due to their size, gas drag exerts only a minor influence on their dynamical behavior, so an initial velocity is needed to bring them into the camera field of view. The source regions of these aggregates are predominantly located near the boundaries of distinct terrains on the surface.

Enhanced Generation of Reactive Oxygen Species via Piezoelectrics based on p-n Heterojunctions with Built-In Electric Field.

Tuning the charge transfer processes through a built-in electric field is an effective way to accelerate the dynamics of electro- and photocatalytic reactions. However, the coupling of the built-in electric field of p-n heterojunctions and the microstrain-induced polarization on the impact of piezocatalysis has not been fully explored. Herein, we demonstrate the role of the built-in electric field of p-type BiOI/n-type BiVO4 heterojunctions in enhancing their piezocatalytic behaviors. The highly crystalline p-n heterojunction is synthesized by using a coprecipitation method under ambient aqueous conditions. Under ultrasonic irradiation in water exposed to air, the p-n heterojunctions exhibit significantly higher production rates of reactive species (·OH, ·O2-, and 1O2) as compared to isolated BiVO4 and BiOI. Also, the piezocatalytic rate of H2O2 production with the BiOI/BiVO4 heterojunction reaches 480 μmol g-1 h-1, which is 1.6- and 12-fold higher than those of BiVO4 and BiOI, respectively. Furthermore, the p-n heterojunction maintains a highly stable H2O2 production rate under ultrasonic irradiation for up to 5 h. The results from the experiments and equation-driven simulations of the strain and piezoelectric potential distributions indicate that the piezocatalytic reactivity of the p-n heterojunction resulted from the polarization intensity induced by periodic ultrasound, which is enhanced by the built-in electric field of the p-n heterojunctions. This study provides new insights into the design of piezocatalysts and opens up new prospects for applications in medicine, environmental remediation, and sonochemical sensors.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. Statement of significanceThrough the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron–hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Fat mass and obesity-associated (FTO) gene is essential for insulin secretion and β-cell function: In vitro studies using INS-1 cells and human pancreatic islets

AimsIn this study, we investigated the role of the FTO gene in pancreatic β-cell biology and its association with type 2 diabetes (T2D). To address this issue, human pancreatic islets and rat INS-1 (832/13) cells were used to perform gene silencing, overexpression, and functional analysis of FTO expression; levels of FTO were also measured in serum samples obtained from diabetic and obese individuals. ResultsThe findings revealed that FTO expression was reduced in islets from hyperglycemic/diabetic donors compared to normal donors. This reduction correlated with decreased INS and GLUT1 expression and increased PDX1, GCK, and SNAP25 expression. Silencing of Fto in INS-1 cells impaired insulin release and mitochondrial ATP production and increased apoptosis in pro-apoptotic cytokine-treated cells. However, glucose uptake and reactive oxygen species production rates remained unaffected. Downregulation of key β-cell genes was observed following Fto-silencing, while Glut2 and Gck were unaffected. RNA-seq analysis identified several dysregulated genes involved in metal ion binding, calcium ion binding, and protein serine/threonine kinase activity. Furthermore, our findings showed that Pdx1 or Mafa-silencing did not influence FTO protein expression. Overexpression of FTO in human islets promoted insulin secretion and upregulated INS, PDX1, MAFA, and GLUT1 expression. Serum FTO levels did not significantly differ between individuals with diabetes or obesity and their healthy counterparts. ConclusionThese findings suggest that FTO plays a crucial role in β-cell survival, metabolism, and function and point to a potential therapeutic utility of FTO in T2D patients.

Sources of Reactive Oxygen Species in Normoxic and Hypoxic Naked Mole-Rat Brain

Oxygen availability dictates the rate of reactive oxygen species production from various cellular sources; excessive ROS accumulation can be cytotoxic. Mitochondria are usually the primary contributors to basal reactive oxygen species generation in the brain; however, xanthine oxidoreductase and nicotinamide adenine dinucleotide phosphate oxidase can also produce considerable reactive oxygen species during hypoxia/reoxygenation. In the brains of most mammals, cellular death accompanies hypoxia-mediated surges in reactive oxygen species production, but this is avoided in the cortex of hypoxia-tolerant naked mole-rats (Heterocephalus glaber). However, the contributions of various reactive oxygen species generators towards total reactive oxygen species homeostasis in naked mole-rat brain is unknown. We hypothesized that mitochondria remain the primary reactive oxygen species generators in naked mole-rat cortex and predicted that pharmacological inhibition of mitochondrial complex I would induce greater fluctuations in superoxide (O2•-) and hydrogen peroxide (H2O2) than inhibition of xanthine oxidoreductase or nicotinamide adenine dinucleotide phosphate oxidase. To test this, we used fluorescence microscopy to measure H2O2 and O2•- production from cortical slices during normoxia and hypoxia while pharmacologically inhibiting mitochondrial complex I, xanthine oxidoreductase, or nicotinamide adenine dinucleotide phosphate oxidase. Unexpectedly, we found xanthine oxidoreductase inhibition induced the greatest increase in O2•- during normoxia and hypoxia (~100% and 70%, respectively). Hypoxic inhibition of nicotinamide adenine dinucleotide phosphate oxidase induced the greatest decrease in H2O2 by ~35% below baseline. Finally, although inhibition of mitochondrial complex I during hypoxia yielded significant fluctuations in O2•- and H2O2, these changes were considerably smaller than fluctuations induced by inhibiting xanthine oxidoreductase or nicotinamide adenine dinucleotide phosphate oxidase. Together, and unlike in other rodent brain, our results suggest that xanthine oxidoreductase is the primary contributor to reactive oxygen species production in naked mole-rat cortex.

Numerical analysis and flamelet modeling of NO[formula omitted] formation in a thermodiffusively unstable premixed hydrogen flame at elevated-pressure conditions

Fuel-lean premixed hydrogen flames are thermodiffusively unstable and cellular structures over a wide range of length-scales are formed due to strong differential diffusion of hydrogen. Pressure promotes the thermodiffusive instabilities due to the increase in Zeldovich number and the relevant reaction pathways. As the local stoichiometry and temperature correlate with the thermodiffusive instabilities, the NOx formation mechanism is expected to be complicated in fuel-lean hydrogen flames at elevated-pressure conditions. In this work, the characteristics and the NOx formation mechanism of thermodiffusively unstable premixed hydrogen flames at elevated-pressure conditions are investigated through direct numerical simulation (DNS). The designed operating conditions were motivated by findings in experiments investigating NOx emissions in pure hydrogen combustion at elevated-pressure conditions. The flame characteristics are assessed by means of the global burning velocity, flame surface area, stretch factor, and PDFs of curvature and length-scale of cellular structures. The conditioned thermo-chemical quantities are analyzed with respect to the progress variable and curvature to illustrate the key correlations. The contributions of elementary reactions to the NOx formation are quantified and the important reaction pathways are identified in a reaction pathway analysis. The global burning velocity is significantly increased with increasing pressure, which mainly results from the increased reactivity. The positive curvature is more prominent in the elevated-pressure case, which results in a higher probability of smaller cells. Different from the atmospheric case, where the NNH reaction pathway is dominant, the N2O reaction pathway is the most important under elevated-pressure conditions, which suggests the strong correlations of NOx formation with curvature values. To incorporate the wide range of curvatures in a flamelet model, an extended flamelet tabulation method based on the composition space model is proposed. The performance of the composition space model in predicting the important radicals and NOx species is evaluated through an a priori analysis. The composition space model gives better predictions of the radicals and the production and consumption rates of the NOx species compared to conventional flamelet models that do not consider the effects of local flame curvature.

The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.

Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.

(Invited) A Novel Dems Approach for Studying Gas Evolution in Pouch Cells

In this study, we designed a novel differential electrochemical mass spectrometry (DEMS) system to in-situ quantify the gas generation in batteries. While a lot of battery gas analyses were carried out by DEMS previously, most of those studies were based on small coin cells or EL cells. The fluid electrolyte and limited amount of active material may make it challenging to quantify the gas generation. The DEMS we designed here can continually sample gas from a small 2.5Ah pouch cell, and it has a similar electrolyte to capacity ratio, 1.8g/Ah, with our production cell. To the best of our knowledge, this is the first DEMS design based on a pouch cell.Moreover, by using flowrate-controlled Ar carrier gas and a reasonable residence time setup, our DEMS design not only can identify volatile electrolyte degradation products throughout battery cycling but also quantify the gaseous species production rates as a function of the state of charge. We found that cell chemistry and operation protocol greatly impact gas product species, the production profile of different gases during cycling, and the total gas quantity. For example, the gas evolution of oxidation products, such as CO2 and CO, is exacerbated by the elevated upper cutoff voltage, while reduction products are only minimally affected. Furthermore, changing the electrolyte SEI former, from EC to FEC, or adding different electrolyte additives can affect the gas product species generation dramatically as well.Therefore, we successfully demonstrated DEMS as a powerful tool to probe the gas evolution behavior in different applications-based batteries, provided valuable data for battery reactivity simulation, and most importantly, provided guidance for electrolyte optimization.

CuO/ZnO Type-II heterojunction modified by rGO nanosheets for improved photocatalytic mineralization of antibiotics

In the present work, CuO/ZnO type-II heterojunction was modified by graphene oxide nanosheets for excellent photocatalytic mineralization of antibiotics under artificial UV light and natural sunlight. For this purpose, CuO/ZnO heterojunction-graphene oxide nanocomposites were synthesized via a facile refluxing method in aqueous media. The synthesized nanocomposites were characterized through diverse characterization techniques such as XRD, FT- IR, Raman, SEM, TEM, and UV–Vis DRS to determine their structural, morphological, and optical properties. XRD analysis confirmed the monoclinic CuO and hexagonal wurtzite ZnO phase in bare CuO/ZnO heterojunction and different CuO/ZnO heterojunction-graphene oxide nanocomposites as well. The optical band gap was found in the range of 3.06–3.19 eV for different nanocomposites. The photocatalytic activity of the bare heterojunction and nanocomposites was performed against the degradation of ciprofloxacin under the irradiation of artificial UV and natural sunlight as well. The highest degradation % of ciprofloxacin was achieved at 96.27 % and 76.44 % under artificial UV and natural sunlight within 120 min, respectively over CuO/ZnO heterojunction with 3 wt% of graphene oxide. The outstanding photocatalytic performance of CuO/ZnO heterojunction-graphene oxide (3 wt%) owing to the high adsorption capacity and synergism between CuO/ZnO and graphene oxide caused the improved separation of charge species resulting higher production rate of reactive oxygen species and prompt degradation of ciprofloxacin.

A co-kurtosis PCA based dimensionality reduction with nonlinear reconstruction using neural networks

For turbulent reacting flow systems, identification of low-dimensional representations of the thermo-chemical state space is vitally important, primarily to significantly reduce the computational cost of device-scale simulations. Principal component analysis (PCA), and its variants, are a widely employed class of methods. Recently, an alternative technique that focuses on higher-order statistical interactions, co-kurtosis PCA (CoK-PCA), has been shown to effectively provide a low-dimensional representation by capturing the stiff chemical dynamics associated with spatiotemporally localized reaction zones. While its effectiveness has only been demonstrated based on a priori analyses with linear reconstruction, in this work, we employ nonlinear techniques to reconstruct the full thermo-chemical state and evaluate the efficacy of CoK-PCA compared to PCA. Specifically, we combine a CoK-PCA-/PCA-based dimensionality reduction (encoding) with an artificial neural network (ANN) based reconstruction (decoding) and examine, a priori, the reconstruction errors of the thermo-chemical state. In addition, we evaluate the errors in species production rates and heat release rates, which are nonlinear functions of the reconstructed state, as a measure of the overall accuracy of the dimensionality reduction technique. We employ four datasets to assess CoK-PCA/PCA coupled with ANN-based reconstruction: zero-dimensional (homogeneous) reactor for autoignition of an ethylene/air mixture that has conventional single-stage ignition kinetics, a dimethyl ether (DME)/air mixture which has two-stage (low and high temperature) ignition kinetics, a one-dimensional freely propagating premixed ethylene/air laminar flame, and a two-dimensional dataset representing turbulent autoignition of ethanol in a homogeneous charge compression ignition (HCCI) engine. Results from the analyses demonstrate the robustness of the CoK-PCA based low-dimensional manifold with ANN reconstruction in accurately capturing the data, specifically from the reaction zones.

Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats

Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether lowering LCAC levels with the anti-ischemia compound 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB) protects brain mitochondrial function and improves neurological outcomes after transient middle cerebral artery occlusion (MCAO). The effects of 14 days of pretreatment with methyl-GBB (5 mg/kg, p.o.) on brain acylcarnitine (short-, long- and medium-chain) concentrations and brain mitochondrial function were evaluated in Wistar rats. Additionally, the mitochondrial respiration and reactive oxygen species (ROS) production rates were determined using ex vivo high-resolution fluorespirometry under normal conditions, in models of ischemia-reperfusion injury (reverse electron transfer and anoxia-reoxygenation) and 24 h after MCAO. MCAO model rats underwent vibrissae-evoked forelimb-placing and limb-placing tests to assess neurological function. The infarct volume was measured on day 7 after MCAO using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with methyl-GBB significantly reduced the LCAC content in brain tissue, which decreased the ROS production rate without affecting the respiration rate, indicating an increase in mitochondrial coupling. Furthermore, methyl-GBB treatment protected brain mitochondria against anoxia–reoxygenation injury. In addition, treatment with methyl-GBB significantly reduced the infarct size and improved neurological outcomes after MCAO. Increased mitochondrial coupling efficiency may be the basis for the neuroprotective effects of methyl-GBB. This study provides evidence that maintaining brain energy metabolism by lowering the levels of LCACs protects against ischemia-induced brain damage in experimental stroke models.

Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles.

Acute kidney injury (AKI) is often caused by ischemia-reperfusion injury (IRI). IRI significantly affects kidney metabolism, which elicits pro-inflammatory responses and kidney injury. The ischemia/reperfusion of the kidney is associated with transient high mitochondrial-derived reactive oxygen species (ROS) production rates. Excessive mitochondrial-derived ROS damages cellular components and, together with other pathogenic mechanisms, elicits a range of acute injury mechanisms that impair kidney function. Mitochondrial-derived ROS production also stimulates epithelial cell secretion of extracellular vesicles (EVs) containing RNAs, lipids, and proteins, suggesting that EVs are involved in AKI pathogenesis. This literature review focuses on how EV secretion is stimulated during ischemia/reperfusion and how cell-specific EVs and their molecular cargo may modify the IRI process. Moreover, critical pitfalls in the analysis of kidney epithelial-derived EVs are described. In particular, we will focus on how the release of kidney epithelial EVs is affected during tissue analyses and how this may confound data on cell-to-cell signaling. By increasing awareness of methodological pitfalls in renal EV research, the risk of false negatives can be mitigated. This will improve future EV data interpretation regarding EVs contribution to AKI pathogenesis and their potential as biomarkers or treatments for AKI.

Investigation of the impact of nitrogen and water vapor dilution in oxidizer stream on flame structure, soot production and extinction of a laminar ethylene-fueled co-flow diffusion flame

This paper discusses the effect of nitrogen (N2) and water vapor (H2O) dilution in oxidizer stream on the flame structure, and soot production and extinction of laminar ethylene (C2H4)-fueled co-flow diffusion flame (CFDF). The total oxidizer stream flow rate is kept constant while varying the flow rates of air, N2, and H2O to achieve the desired oxygen concentration called oxygen index (OI). As OI reduces, the flame starts to lift off from the burner surface and shows upward and downward oscillations before extinction through blow-off. The OI at which the flame blows off is called the limited oxygen index (LOI), and it depends on burner configuration, fuel, and oxidizer flow conditions. LOI value for C2H4-fueled laminar CFDF were found to be 12.4% and 14% when the diluent was N2 and H2O, respectively. The experiment and simulation results are presented from 21% O2 concentration in oxidizer to very low oxygen concentration in oxidizer close to extinction. Through quantitative measurements of soot volume fraction (SVF), the result shows a notable reduction in the peak concentrations of SVF as the OI decreases. This decrease is more pronounced with H2O than N2 dilution. One-dimensional (1D) opposed flow diffusion flame simulations are performed to understand various effects of the addition of diluents like H2O and N2. It is observed that in addition to inert, thermal and diffusion effect of H2O in reduction of flame temperature and temperature-dependent production rate of key species, H2O also affects flame chemistry through OH + H2 = H + H2O, 2OH = O + H2O. As a result there is a further drop in the concentration of active radicals (like H, O) which leads to quicker soot inhibition and flame extinction.

Assessment of Bacillus subtilis fermented Caulerpa microphysa byproduct as feed additive on the growth performance, immune regulation and disease resistance of white shrimp (Litopenaeus vannamei)

In this study, the immunomodulatory and antioxidant activity of fermented Caulerpa microphysa byproduct (FCMB) by Bacillus subtilis was evaluated, and its potential as a feed additive for white shrimp (Litopenaeus vannamei) was explored. In vitro experiments showed that the FCMB supernatant contained polysaccharides, polyphenols and flavonoids, and exhibited antioxidant properties as assessed by various antioxidant assays. Additionally, the FCMB supernatant was found to increase the production rate of reactive oxygen species and the activity of phenoloxidase in hemocytes in vitro. Furthermore, the results of the in vivo feeding trial showed that dietary 5 g kg−1 FCMB significantly improved the weight gain and specific growth rate of white shrimp after 56 days of feeding. Although there were no significant differences in total hemocyte count, phagocytosis, superoxide anion production rate, and phenoloxidase activity among the experimental groups, upregulation of immune-related genes was observed, particularly in the hepatopancreas and hemocytes of shrimps fed with 5 g or 50 g FCMB per kg feed, respectively. In the pathogen challenge assay, white shrimp fed with 5 % FCMB exhibited a higher survival rate compared to the control group following Vibrio parahaemolyticus challenge. Therefore, it is concluded that the fermented byproduct of C. microphysa, FCMB, holds potential as a feed additive for enhancing the growth performance and disease resistance against V. parahaemolyticus in white shrimp.

Nrf2 protein in melanoma progression, as a new means of treatment.

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch-like ECH-associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1-Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1-Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.

A blueprint for a synthetic genetic feedback optimizer

Biomolecular control enables leveraging cells as biomanufacturing factories. Despite recent advancements, we currently lack genetically encoded modules that can be deployed to dynamically fine-tune and optimize cellular performance. Here, we address this shortcoming by presenting the blueprint of a genetic feedback module to optimize a broadly defined performance metric by adjusting the production and decay rate of a (set of) regulator species. We demonstrate that the optimizer can be implemented by combining available synthetic biology parts and components, and that it can be readily integrated with existing pathways and genetically encoded biosensors to ensure its successful deployment in a variety of settings. We further illustrate that the optimizer successfully locates and tracks the optimum in diverse contexts when relying on mass action kinetics-based dynamics and parameter values typical in Escherichia coli.