Oxidation Of Residues Research Articles

Is autism a PIN1 deficiency syndrome? A proposed etiological role for glyphosate.

Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.

Synergistic effects of plasma-activated water (PAW) and electrochemical treatment on the color of tuna slices

Recent advances in the field of meat processing have promoted the exploration of innovative methods to enhance the visual appeal of meat products. This research introduces a new approach that involves the combination of plasma-activated water (PAW) and electrochemical processes to improve the redness of tuna meat. The study revealed that subjecting PAW to electrochemical treatment at −0.85 V for 5 min significantly enhanced its color-enhancing properties. This enhancement is linked to the conversion of nitrites and nitrates into nitric oxide (NO) during the electrochemical process, which then interact with myoglobin to form nitrosomyoglobin (NOMb), resulting in the desired pink coloration. While a slight rise in residual nitrite and lipid oxidation was noted after treatment, these levels remained within acceptable limits according to prevailing safety standards, ensuring consumer safety. This study sets the stage for the potential utilization of a combined approach involving PAW and electrochemical methods in meat processing, offering the prospect of developing more appealing and commercially viable meat products.

THE INFLUENCE OF AGE, PHYSICAL ACTIVITY, SMOKING AND THE PRESENCE OF MYOCARDIAL INFARCTION AND THYROID DISEASES IN THE FAMILY ON THE LEVEL OF ALDEHYDIC AND KETONIC DERIVATIVES OF OXIDATIVE MODIFICATION OF PROTEINS IN THE BLOOD OF WOMEN AND MEN WITH MYOCARDIAL INFARCTS AND HYPOTHYROIDISM

The importance of thyroid hormones in maintaining homeostasis of the cardiovascular system can be inferred from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism and low triiodothyronine syndrome - adversely affect the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidemia, endothelial dysfunction, changes in blood pressure, and the direct effects of thyroid hormones on the myocardium. Purpose: analysis of changes in the concentration of markers of oxidative stress, e.g. oxidation of protein amino acid residues [concentration of aldehydic and ketonic derivatives of oxidatively modified proteins (OMP)] in the blood of individuals with hypothyroidism and/or myocardial infarcts, living in central Pomeranian region, depending on age, physical activity, smoking and the presence of myocardial infarcts and thyroid diseases in the family. Methodology. The level of oxidative stress markers was assessed among 225 individuals, i.e. 132 males (58.67%) and 93 females (41.33%) aged 35-71 years residing in central Pomeranian region. In the obtained blood, an assessment of levels of aldehydic and ketonic derivatives of oxidatively modified protein analyses was carried out. Scientific novelty. According to our research, the level of aldehydic derivatives of oxidative modification of proteins was significantly higher in the elderly (more than 55 years old), and the level of ketonic derivatives was higher in younger individuals (less than 55 years old) with myocardial infarction and with both myocardial infarction and hypothyroidism. This proves the intensification of oxidative stress in both presented diseases, both among the elderly and younger individuals. The highest level of aldehydic and ketonic derivatives of oxidative modification of proteins was noted among individuals with myocardial infarctions and hypothyroidism with low physical activity and among non-smokers who suffer from hypothyroidism and additionally suffered myocardial infarctions, which may indicate an increase in oxidative stress at these diseases, regardless of physical activity and smoking. The highest level of aldehydic derivatives was noted in the group of individuals with myocardial infarction and hypothyroidism with myocardial infarction in family history, which may indicate an increase in oxidative stress in both diseases, especially in this studied group. The highest level of oxidative modification of proteins was noted among individuals with myocardial infarction and hypothyroidism, individuals with thyroid diseases in their family history, as well as those with no thyroid diseases in their family history. This proves the intensification of oxidative stress in both presented diseases, regardless of the factor of thyroid diseases in the family history. Conclusions. In the course of myocardial infarction, the level of aldehydic derivatives of oxidatively modified proteins is affected by gender, while the level of ketonic derivatives of oxidatively modified proteins is affected by the presence of a myocardial infarction in the family history. The level of aldehydic derivatives of oxidative modification of proteins in individuals with hypothyroidism is influenced by low physical activity and age over 55, while the level of ketonic derivatives of oxidative modification of proteins is affected by the gender of the individuals. In the course of myocardial infarction and hypothyroidism, the level of aldehydic derivatives of protein oxidative modification is affected by age and physical activity, while the level of ketonic derivatives of protein oxidative modification is affected by the age of individuals.

Catalytic post-treatment of homogeneous Ag–S2O8 and Cu–H2O2 advanced oxidation processes: Revealing the importance of capacitive-Faradaic electrochemical structure of Pt/AC

Implementation of homogeneous advanced oxidation processes (HAOPs) catalysed by Cu and Ag metals is limited due to high residual concentrations of oxidants and dissolved metals. The proposed post-treatment process starts with recirculation of H2-enriched HAOP-treated water through the Pt-loaded activated carbon (AC). Hydrogen oxidation reaction (HOR) on Pt results in degradation of oxidants while silver and/or copper ions are reduced and deposited on the catalytic media. The subsequent aeration of the catalyst results in oxygen reduction reaction (ORR) and oxidation of the metals back into ionic forms. This allows the homogeneous metal catalysts to be reused in multiple HAOP cycles.The capacitive-Faradaic electrochemical structure of the Pt/AC catalyst with Pt acting as a Faradaic electrode and AC as a capacitive electrode plays an important role in the process. The HOR on Pt/AC results in accumulation of electrons in electrical double layer of AC. These electrons can be effectively used in a subsequent H2-free reduction of metal ions and oxidants. Thus, the degradation of H2O2 and S2O82− and reduction of Cu2+ and Ag + ions proceed much faster if the H2-step of the process is split into two sub-processes: (i) hydrogenation of Pt/AC catalyst in an inert Na2SO4 solution to pre-charge the Pt/AC with electrons originating at HOR, followed by (ii) catalytic reduction of oxidants and metal ions by the capacitively stored electrons.The process was investigated using Ag–S2O82− ([S2O82−]0 = 25 mM; [Ag+]0 = 50 mg/L) and Cu–H2O2 ([H2O2]0 = 100 mM, [Cu]0 = 635 mg/L) solutions. Total degradation of oxidants was achieved within <2 h and complete metals’ recovery was obtained. Several cycles of HAOP experiments were performed for the degradation of 1,4-dioxane (10 mg/L) and phenol (25 mg/L) using Ag– S2O82− and Cu–H2O2 HAOPs, respectively. The residual oxidants were completely degraded in all experiments. The reactivation of Pt/AC catalysts inhibited by phenol derivatives was achieved by hydrogenation in Na2SO4 solution (i.e., using the pre-charge approach).

Mechanism of Methylene Blue Inducing the Disulfide Bond Formation of Tubulin-Associated Unit Proteins.

Methylene blue (MB) has recently completed a Phase-3 clinical trial as leuco-methylthioninium (LMT) bis(hydromethanesulfonate) for treating Alzheimer's disease. Herein, we investigated the mechanism underlying the MB inhibition of tubulin-associated unit (tau) aggregation by focusing on tau monomers. We found that MB causes disulfide bond formation, resulting in strong nuclear magnetic resonance chemical shift perturbations in a large area of tau proteins. The oxidized form of MB, namely methylthioninium (MT+), specifically catalyzed the oxidation of cysteine residues in tau proteins to form disulfide bonds directly using O2. This process is independent of the MT+-to-LMT redox cycle. Moreover, MT+ preferentially oxidized C291 and C322 in the lysine-rich R2 and R3 domains. Under in vivo brain physoxia conditions, LMT may convert to MT+, possibly interfering with tau fibrillation via disulfide bond formation.

Synthesis of core–shell silicon–carbon nanocomposites via in-situ molten salt-based reduction of rice husks: A promising approach for the manufacture of lithium-ion battery anodes

Silicon (Si) has gained substantial interest as a potential component of lithium-ion battery (LIB) anodes due to its high theoretical specific capacity. However, conventional methods for producing Si for anodes involve expensive metal reductants and stringent reducing environments. This paper describes the development of a calcium hydride (CaH2)–aluminum chloride (AlCl3) reduction system that was used for the in-situ low-temperature synthesis of a core–shell structured silicon–carbon (Si–C) material from rice husks (RHs), and the material was denoted RHs-Si@C. Moreover, as an LIB anode, RHs-Si@C exhibited exceptional cycling performance, exemplified by 90.63 % capacity retention at 5 A g−1 over 2000 cycles. Furthermore, the CaH2–AlCl3 reduction system was employed to produce Si nanoparticles (Si NPs) from RHs (R-SiO2, where SiO2 is silica) and from commercial silica (C-SiO2). The R-SiO2-derived Si NPs exhibited a higher residual silicon oxides (SiOx) content than the C-SiO2-derived Si NPs. This was advantageous, as there was sufficient SiOx in the R-SiO2-derived Si NPs to mitigate the volumetric expansion typically associated with Si NPs, resulting in enhanced cycling performance. Impressively, Si NPs were fabricated on a kilogram scale from C-SiO2 in a yield of 82 %, underscoring the scalability of the low-temperature reduction technique.

Physiological, Transcriptome, and Metabolome Analyses Reveal the Tolerance to Cu Toxicity in Red Macroalgae Gracilariopsis lemaneiformis.

Heavy metal copper (Cu) will inevitably impact the marine macroalgae Gracilariopsis lemaneiformis (G. lemaneiformis), which is a culture of economic importance along China's coastline. In this study, the detoxification mechanism of Cu stress on G. lemaneiformis was revealed by assessing physiological indicators in conjunction with transcriptome and metabolome analyses at 1 d after Cu stress. Our findings revealed that 25 μM Cu stimulated ROS synthesis and led to the enzymatic oxidation of arachidonic acid residues. This process subsequently impeded G. lemaneiformis growth by suppressing photosynthesis, nitrogen metabolism, protein synthesis, etc. The entry of Cu ions into the algae was facilitated by ZIPs and IRT transporters, presenting as Cu2+. Furthermore, there was an up-regulation of Cu efflux transporters HMA5 and ABC family transporters to achieve compartmentation to mitigate the toxicity. The results revealed that G. lemaneiformis elevated the antioxidant enzyme superoxide dismutase and ascorbate-glutathione cycle to maintain ROS homeostasis. Additionally, metabolites such as flavonoids, 3-O-methylgallic acid, 3-hydroxy-4-keto-gama-carotene, and eicosapentaenoic acid were up-regulated compared with the control, indicating that they might play roles in response to Cu stress. In summary, this study offers a comprehensive insight into the detoxification mechanisms driving the responses of G. lemaneiformis to Cu exposure.

The Reducing Agent Dithiothreitol Modulates the Ventilatory Responses That Occur in Freely Moving Rats during and following a Hypoxic-Hypercapnic Challenge.

The present study examined the hypothesis that changes in the oxidation-reduction state of thiol residues in functional proteins play a major role in the expression of the ventilatory responses in conscious rats that occur during a hypoxic-hypercapnic (HH) gas challenge and upon return to room air. A HH gas challenge in vehicle-treated rats elicited robust and sustained increases in minute volume (via increases in frequency of breathing and tidal volume), peak inspiratory and expiratory flows, and inspiratory and expiratory drives while minimally affecting the non-eupneic breathing index (NEBI). The HH-induced increases in these parameters, except for frequency of breathing, were substantially diminished in rats pre-treated with the potent and lipophilic disulfide-reducing agent, L,D-dithiothreitol (100 µmol/kg, IV). The ventilatory responses that occurred upon return to room air were also substantially different in dithiothreitol-treated rats. In contrast, pre-treatment with a substantially higher dose (500 µmol/kg, IV) of the lipophilic congener of the monosulfide, N-acetyl-L-cysteine methyl ester (L-NACme), only minimally affected the expression of the above-mentioned ventilatory responses that occurred during the HH gas challenge or upon return to room air. The effectiveness of dithiothreitol suggests that the oxidation of thiol residues occurs during exposure to a HH gas challenge and that this process plays an essential role in allowing for the expression of the post-HH excitatory phase in breathing. However, this interpretation is contradicted by the lack of effects of L-NACme. This apparent conundrum may be explained by the disulfide structure affording unique functional properties to dithiothreitol in comparison to monosulfides. More specifically, the disulfide structure may give dithiothreitol the ability to alter the conformational state of functional proteins while transferring electrons. It is also possible that dithiothreitol is simply a more efficient reducing agent following systemic injection, although one interpretation of the data is that the effects of dithiothreitol are not due to its reducing ability.

Hot Hydrogen Testing of W-Coated UN Kernels in a Mo30W Matrix

Ceramic uranium mononitride (UN) is being considered as a reactor fuel for nuclear thermal propulsion. To avoid or reduce the dissociation of UN at the high temperatures needed, embedding it in a metallic matrix (cermet) has been proposed. To assess the viability of this concept, hot hydrogen testing of tungsten-coated UN kernels embedded in a Mo-30 wt% W (Mo30W) alloy matrix has been performed at temperatures from 1800°C to 2300°C. Both the isolated kernels and kernels consolidated by spark plasma sintering in the Mo30W matrix were tested. In addition to direct observations and mass loss measurements, the samples were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) after each run. The decomposition of UN started at 1800°C despite the coating and matrix, and increased at 2000°C. Uranium seeped through the tungsten grain boundaries of the coating at all temperatures. The consolidated sample expanded irregularly at 2000°C through the formation of voids, and SEM/EDS analysis showed uranium-containing veins in the matrix consisting of U2Mo according to the XRD data. The observed pore generation at 2000°C was explained by the formation of water vapor from residual oxides and diffused hydrogen. At 2200°C and above, both the kernels and the consolidated samples melted through the formation of uranium or low–melting point uranium-molybdenum alloys.

Interfacial characteristics, interfacial oxide evolution and bonding mechanism of 2219 aluminum alloy joints manufactured by hot-compression bonding

The bonding joints of 2219 aluminum alloy with different deformations of 30%, 45% and 55% were fabricated using hot-compression bonding, and subsequent subjected to homogenization treatment. The interfacial microstructure and interfacial oxide evolution of the bonding joints were systematically investigated. The results showed that increasing deformation can effectively reduce the formation of interfacial voids and promote the interfacial grain boundary migration (IGBM). As the deformation increased from 30% to 55%, the flat bonding interface transformed into curved grain boundaries, and ultimately being occupied by dynamically recrystallized (DRXed) grains. The development of IGBM and interfacial DRXed grains is crucial for ensuring high-quality bonding joints. At 55% deformation, the interface bonding strength reached 156.2 MPa, corresponding to 98.1% of the matrix bonding strength. In addition, the residual interfacial oxide film Al2O3 reacted with MgO and transformed into MgAl2O4 spinel. The final evolution products at the bonding interface were the mixture of MgO, Al2Cu, Al2O3, and MgAl2O4. The bonding interface at 55% deformation successfully achieved relatively clean atomic bonding after homogenization. Based on interfacial void closure, interfacial oxide film fragmentation and evolution, and interfacial recrystallization, the bonding mechanism of 2219 aluminum alloy joints was proposed. These findings contribute to our understanding of the interfacial bonding process in metal solid bonding.

Facile Reactive Oxygen Species-Scavenging Supramolecular Hydrogel to Promote Diabetic Wound Healing.

Chronic wound healing impairment is a significant complication in diabetes. Hydrogels that maintain wound moisture and enable sustained drug release have become prominent for enhancing chronic wound care. Particularly, hydrogels that respond to reactive oxygen species (ROS) are sought-after for their dual capacity to mitigate ROS and facilitate controlled drug delivery at the wound site. We have strategically designed an ROS-responsive and scavenging supramolecular hydrogel composed of the simple hexapeptide Glu-Phe-Met-Phe-Met-Glu (EFM). This hydrogelator, composed solely of canonical amino acids without additional ROS-sensitive motifs, forms a hydrogel rapidly upon sonication. Interaction with ROS leads to the oxidation of Met residues to methionine sulfoxide, triggering hydrogel disassembly and consequent payload release. Cellular assays have verified their biocompatibility and efficacy in promoting cell proliferation and migration. In vivo investigations underscore the potential of this straightforward hydrogel as an ROS-scavenger and drug delivery vehicle, enhancing wound healing in diabetic mice. The simplicity and effectiveness of this hydrogel suggest its broader biomedical applications in the future.

Insights into the Multifaceted Roles of Thioredoxin-1 System: Exploring Knockout Murine Models.

Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex regulatory mode of protein function. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS), but they are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin, and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review, we have specifically focused on the available literature on thioredoxin-1 system transgenic models that include thioredoxin and thioredoxin reductase proteins. As the identification of thioredoxin protein targets is technically challenging, the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain.

Quenching residual H2O2 from UV/H2O2 with granular activated carbon: A significant impact of bicarbonate

UV/H2O2 has been used as an advanced oxidation process to remove organic micropollutants from drinking water. It is essential to quench residual H2O2 to prevent increased chlorine demand during chlorination/chloramination and within distribution systems. Granular activated carbon (GAC) filter can quench the residual oxidant and eliminate some of the dissolved organic matter. However, knowledge on the kinetics and governing factors of GAC quenching of residual H2O2 from UV/H2O2 and the mechanism underlying the enhancement of the process by HCO3− is limited. Therefore, this study aimed to analyse the kinetics and influential factors, particularly the significant impact of bicarbonate (HCO3−). H2O2 decomposition by GAC followed first-order kinetics, and the rate constants normalised by the GAC dosage (kn) were steady (1.6 × 10−3 L g−1 min−1) with variations in the GAC dosage and initial H2O2 concentration. Alkaline conditions favour H2O2 quenching. The content of basic groups exhibited a stronger correlation with the efficiency of GAC in quenching H₂O₂ than did the acidic groups， with their specific kn values being 8.9 and 2.4 min−1 M−1, respectively. The presence of chloride, sulfate, nitrate, and dissolved organic matter inhibited H2O2 quenching, while HCO3− promoted it. The interfacial hydroxyl radical (HO•) zones were visualised on the GAC surface, and HCO3− addition increased the HO• concentration. HCO3− increased the concentration of persistent free radicals (PFRs) on the GAC surface, which mainly contributed to HO• generation. A significant enhancement of HCO3− on H2O2 quenching by GAC was also verified in real water. This study revealed the synergistic mechanism of HCO3− and GAC on H2O2 quenching and presents the potential applications of residual H2O2 in the H2O2-based oxidation processes.

YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as gefitinib and osimertinib have primarily been used as first-line treatments for patients with EGFR-activating mutations in non-small cell lung cancer (NSCLC). Novel biomarkers are required to distinguish patients with lung cancer who are resistant to EGFR-TKIs. The aim of the study is to investigate the expression and functional role of YES1, one of the Src-family kinases, in EGFR-TKI-resistant NSCLC. YES1 expression was elevated in gefitinib-resistant HCC827 (HCC827/GR) cells, harboring EGFR mutations. Moreover, HCC827/GR cells exhibited increased reactive oxygen species (ROS) levels compared to those of the parent cells, resulting in the phosphorylation/activation of YES1 due to oxidation of the cysteine residue. HCC827/GR cells showed elevated expression levels of YES1-associated protein 1 (YAP1), NF-E2-related factor 2 (Nrf2), cancer stemness-related markers, and antioxidant proteins compared to those of the parent cells. Knockdown of YES1 in HCC827/GR cells suppressed YAP1 phosphorylation, leading to the inhibition of Bcl-2, Bcl-xL, and Cyclin D1 expression. Silencing YES1 markedly attenuated the proliferation, migration, and tumorigenicity of HCC827/GR cells. Dasatinib inhibited the proliferation of HCC827/GR cells by targeting YES1-mediated signaling pathways. Furthermore, the combination of gefitinib and dasatinib demonstrated a synergistic effect in suppressing the proliferation of HCC827/GR cells. Notably, YES1- and Nrf2-regulated genes showed a positive regulatory relationship in patients with lung cancer and in TKI-resistant NSCLC cell lines. Taken together, these findings suggest that modulation of YES1 expression and activity may be an attractive therapeutic strategy for the treatment of drug-resistant NSCLC.

Formation mechanism of (Ti, Zr, Hf)C medium-entropy carbide derived from polymer precursors and its modification on the ablative mechanism of C/C-SiC composites

Medium-entropy carbide (MEC) of (Ti, Zr, Hf)C was synthesized and its modification on the ablative mechanism of C/C-SiC composites was investigated. After 60 s oxyacetylene flame test, the mass and linear ablation rates were 1.43 mg/s and 11.1 μm/s, respectively. The evolution of ceramics oxide scale dominated the anti-ablation process, which transfers from (Ti, Zr, Hf)xCyOz, (Ti, Zr, Hf)xSiyOz to (Ti, Zr, Hf)O2, (Zr, Hf)TiO4. With further evaporation of SiO2, the generated (Ti, Zr, Hf)O2 skeleton and the residual liquid oxides ((Zr, Hf)TiO4 and (Zr, Hf)SiO4) can block the oxygen channel and further reduce oxidation of the inner matrix.

Methionine Alkylation as an Approach to Quantify Methionine Oxidation Using Mass Spectrometry.

Post-translational oxidation of methionine residues can destabilize proteins or modify their functions. Although levels of methionine oxidation can provide important information regarding the structural integrity and regulation of proteins, their quantitation is often challenging as analytical procedures in and of themselves can artifactually oxidize methionines. Here, we develop a mass-spectrometry-based method called Methionine Oxidation by Blocking with Alkylation (MObBa) that quantifies methionine oxidation by selectively alkylating and blocking unoxidized methionines. Thus, alkylated methionines can be used as a stable proxy for unoxidized methionines. Using proof of concept experiments, we demonstrate that MObBa can be used to measure methionine oxidation levels within individual synthetic peptides and on proteome-wide scales. MObBa may provide a straightforward experimental strategy for mass spectrometric quantitation of methionine oxidation.

Research on the Erosion of Gun Barrel Based on Vented Vessel Tests

The vented vessel test, as an alternation of the firing practice, is implemented to reconstruct the deterioration process of the gun barrel suffering the thermochemical erosion by propellant combustion gas. High pressure of over 300 MPa with a duration exceeding 20 ms is applied on the rifled specimen. A phase transition layer about 136 μm is observed by scanning electron microscopy (SEM) from the cross section of the test specimen. Some residual oxidation products of the iron can be detected by energy dispersive x-ray spectroscopy (EDS) on parts of the inner surface. A comprehensive erosion analysis is conducted, which estimates that the mass loss of the specimen is mainly attributed to the periodical formation and peeling of the chemical reaction layer on the bore surface. The most severely eroded part is located on the corner of the land. On the basis of the examined erosion mechanisms, a proper thermochemical erosion model is employed. The mass dissipation and the geometry evolution under continuous firing are simulated using finite element method (FEM). The simulation phenomenon shows good consistency with results of the experimental tests.

MAT gene deregulation and liver cancer

Rodent models with low heterogeneity premalignant and malignant lesions provide a valuable contribution to hepatocellular carcinoma (HCC) pathogenesis in the field of research. Studies have been performed in transgenic mice, and rodent strains on signaling pathways deregulation in hepatocarcinogenesis with varying susceptibilities, and human HCC subtypes. Because ethionine, an antagonist of methionine, causes cancer and methyl-deficient diets cause steatohepatitis, followed by the development of HCC, researchers began to look into mechanisms regulating availability of S-adenosylmethionine (SAM) and its role in liver injury, including HCC development. Cirrhotic livers have decreased methionine adenosyltransferase (MATI/III) levels due to oxidation of cysteine residues in the ATP-binding site. MATII upregulation is inhibited by its reaction product, leading to MATI/III downregulation. Decreased MATI/III: MATII activity ratio, along with increased SAM decarboxylation for polyamine synthesis, results in decreased SAM. Some of the molecular pathways associated with specific cancer phenotypes are evolutionarily conserved, according to previous comparative functional genomics research. Cell cycle regulators (WNT/FZD, PI3K/AKT, and MAPK) and key genes (MAPK, IKK/NF-kB) are upregulated in human and rodent HCC progression. Pseudoprognostic markers for HCC include MAT1A/MAT2A switch. Changes in MAT1A expression and SAM levels occur during hepatocarcinogenesis. No evidence of SAM’s therapeutic effect on HCC has been found. The effects of stable MAT1A overexpression or MAT2A/MAT2B inhibition in vivo should be studied first. MAT2A or MAT2B-silenced HepG2 cells proliferate less in leptin. However, intracellular viral vector transduction in vivo has many limitations. This review interprets recent advances in SAM metabolism deregulation in liver injury predisposing to HCC and determining HCC prognosis.

High-Entropy Diborides-Silicon Carbide Composites by Reactive and Non-Reactive Spark Plasma Sintering: A Comparative Study.

The reactive spark plasma sintering (R-SPS) method was compared in this work with the two-step SHS-SPS route, based on the combination of the self-propagating high-temperature synthesis (SHS) with the SPS process, for the fabrication of dense (Hf0.2Mo0.2Ti0.2Ta0.2Nb0.2)B2-SiC and (Hf0.2Mo0.2Ti0.2Ta0.2Zr0.2)B2-SiC ceramics. A multiphase and inhomogeneous product, containing various borides, was obtained at 2000 °C/20 min by R-SPS from transition metals, B4C, and Si. In contrast, if the same precursors were first reacted by SHS and then processed by SPS under the optimized condition of 1800 °C/20 min, the desired ceramics were successfully attained. The resulting sintered samples possessed relative densities above 97% and displayed uniform microstructures with residual oxide content <2.4 wt.%. The presence of SiC made the sintering temperature milder, i.e., 150 °C below that needed by the corresponding additive-free system. The fracture toughness was also markedly improved, particularly when considering the Nb-containing system processed at 1800 °C/20 min, whereas the fracture toughness progressively decreased (from 7.35 to 5.36 MPa m1/2) as the SPS conditions became more severe. SiC addition was found to inhibit the volatilization of metal oxides like MoO3 formed during oxidation experiments, thus avoiding mass loss in the ceramics. The benefits above also likely took advantage of the fact that the two composite constituents were synthesized in parallel, according to the SHS-SPS approach, rather than being produced separately and combined subsequently, so that strong interfaces between them were formed.

Secondary Modification of S100B Influences Anti Amyloid-β Aggregation Activity and Alzheimer's Disease Pathology.

Proteinaceous aggregates accumulate in neurodegenerative diseases such as Alzheimer's Disease (AD), inducing cellular defense mechanisms and altering the redox status. S100 pro-inflammatory cytokines, particularly S100B, are activated during AD, but recent findings reveal an unconventional molecular chaperone role for S100B in hindering Aβ aggregation and toxicity. This suggests a potential protective role for S100B at the onset of Aβ proteotoxicity, occurring in a complex biochemical environment prone to oxidative damage. Herein, we report an investigation in which extracellular oxidative conditions are mimicked to test if the susceptibility of S100B to oxidation influences its protective activities. Resorting to mild oxidation of S100B, we observed methionine oxidation as inferred from mass spectrometry, but no cysteine-mediated crosslinking. Structural analysis showed that the folding, structure, and stability of oxidized S100B were not affected, and nor was its quaternary structure. However, studies on Aβ aggregation kinetics indicated that oxidized S100B was more effective in preventing aggregation, potentially linked to the oxidation of Met residues within the S100:Aβ binding cleft that favors interactions. Using a cell culture model to analyze the S100B functions in a highly oxidative milieu, as in AD, we observed that Aβ toxicity is rescued by the co-administration of oxidized S100B to a greater extent than by S100B. Additionally, results suggest a disrupted positive feedback loop involving S100B which is caused by its oxidation, leading to the downstream regulation of IL-17 and IFN-α2 expression as mediated by S100B.