Using the High-Entropy Approach to Obtain Multimetal Oxide Nanozymes: Library Synthesis, In Silico Structure-Activity, and Immunoassay Performance.

High-entropy nanomaterials exhibit exceptional mechanical, physical, and chemical properties, finding applications in many industries. Peroxidases are metalloenzymes that accelerate the decomposition of hydrogen peroxide. This study uses the high-entropy approach to generate multimetal oxide-based nanozymes with peroxidase-like activity and explores their application as sensors in ex vivo bioassays. A library of 81 materials was produced using a coprecipitation method for rapid synthesis of up to 100 variants in a single plate. The A and B sites of the magnetite structure, (AA')(BB'B'')2O4, were substituted with up to six different cations (Cu/Fe/Zn/Mg/Mn/Cr). Increasing the compositional complexity improved the catalytic performance; however, substitutions of single elements also caused drastic reductions in the peroxidase-like activity. A generalized linear model was developed describing the relationship between material composition and catalytic activity. Binary interactions between elements that acted synergistically or antagonistically were identified, and a single parameter, the mean interaction effect, was observed to correlate highly with catalytic activity, providing a valuable tool for the design of high-entropy-inspired nanozymes.

Exploring the effects of varying levels of selenium-chitosan on production performance, egg quality, and immune health in laying japanese quail.

The purpose of this research was to see how different levels of Se-chitosan, a novel organic source of Se, affected the production performance, egg quality, egg Se concentration, microbial population, immunological response, antioxidant status, and yolk fatty acid profile of laying Japanese quail. This experiment used a totally randomized design, with 5 treatments, 6 repeats, and 10 birds in each repetition. The dietary treatment groups were as follows: no Se supplementation (control group), 0.2 mg/kg Na-selenite supplementation, and 0.2, 0.4, and 0.6 mg/kg Se-chitosan supplementation. The feed conversion ratio (FCR) improved linearly in quails fed different levels of Se-chitosan compared to the control group (P < 0.05). Furthermore, Se-chitosan at concentrations of 0.2 and 0.4 mg/kg demonstrated both linear and quadratic increases in albumen height, Haugh unit, and yolk color in fresh eggs compared to the control group. Additionally, Se-chitosan contributed to enhanced shell thickness and strength, along with an increased Se concentration in the yolk. Se-chitosan supplementation at different levels linearly and quadratically reduced coliforms (COL) while increasing lactic acid bacteria (LAB)/coliform ratios (P < 0.05). Se-chitosan supplementation linearly and quadratically increased the total antibody response to sheep red blood cells (SRBC) and IgG titers (P < 0.05). It also linearly decreased the level of malondialdehyde in fresh and stored egg yolks and increased the activity of antioxidant enzymes catalase and glutathione peroxidase linearly, and superoxide dismutase (SOD) both linearly and quadratically in quail blood serum (P < 0.05). Additionally, supplementation of Se-chitosan at levels of 0.2 and 0.6 mg/kg linearly decreased the ∑ n-6 PUFA/∑ n-3 PUFA ratio in the yolk compared to the control group (P < 0.05). It can be concluded that incorporating Se-chitosan as a novel organic source of Se in the diet of laying quails can enhance production performance, egg quality, egg Se concentration, yolk lipid oxidation, microbial population, immune response, antioxidant enzyme activity, and yolk fatty acid profile.

Magnetic Hollow Fibers of Covalent Organic Frameworks (COF) for Pollutant Degradation and Adsorptive Removal.

The shaping of covalent organic frameworks (COFs), requiring the conversion of non-processible COF powders into applicable architectures with additional functionality, remains a challenge. Using pre-electrospun polymer fibers as a sacrificial template, herein, we report a green synthesis of an architecture in the form of COF hollow fibers with an inner layer of peroxidase-like iron oxide nanoparticles as a catalytic material. When compared to peroxidase-like pristine iron oxide nanoparticles, these COF hollow fibers demonstrate higher catalytic breakdown of crystal violet due to their peroxidase-like activity via advanced oxidation process. Furthermore, as a potential adsorbent, hollow COF fibers exhibit significantly effective adsorption capacity and removal efficiency of organic solvent and oil from water. Because of their magnetic nature, COF hollow fibers can be easily recovered and have exhibited high recycling stability for both catalytic dye degradation and organic solvent removal from water.

TYMS Knockdown Suppresses Cells Proliferation, Promotes Ferroptosis via Inhibits PI3K/Akt/mTOR Signaling Pathway Activation in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by a grim prognosis and numerous challenges. The objective of our study was to examine the role of thymidylate synthase (TYMS) in TNBC and its impact on ferroptosis. The expression of TYMS was analyzed in databases, along with its prognostic correlation. TYMS positive expression was identified through immunohistochemistry (IHC), while real-time quantitative PCR (qRTPCR) was employed to measure TYMS mRNA levels in various cell lines. Western blotting was utilized to assess protein expression. Cell proliferation, mobility, apoptosis, and reactive oxygen species (ROS) levels were evaluated using CCK8, wound scratch healing assay, transwell assay, and flow cytometry, respectively. Additionally, a tumor xenograft model was established in BALB/c nude mice for further investigation. Tumor volume and weight were measured, and histopathological analysis using hematoxylin and eosin (H&E) staining was conducted to assess tumor tissue changes. IHC staining was employed to detect the expression of Ki67 in tumor tissues. High expression of TYMS was observed in TNBC and was found to be correlated with poor prognosis in patients. Among various cell lines, TYMS expression was highest in BT549 cells. Knockdown of TYMS resulted in suppression of cell proliferation and mobility, as well as promotion of apoptosis. Furthermore, knockdown of TYMS led to increased accumulation of ROS and Fe2+ levels, along with upregulation of ACLS4 expression and downregulation of glutathione peroxidase 4 (GPX4) expression. In vivo studies showed that knockdown of TYMS inhibited tumor growth. Additionally, knockdown of TYMS was associated with inhibition of mTOR, p-PI3K, and p-Akt expression. Our research showed that the knockdown of TYMS suppressed the TNBC progression by inhibited cells proliferation via ferroptosis. Its underlying mechanism is related to the PI3K /Akt pathway. Our study provides a novel sight for the suppression effect of TYMS on TNBC.

APEX2-Mediated Proximity Protein Labeling in Dictyostelium.

Largely due to its simplicity, while being more like human cells compared to other experimental models, Dictyostelium continues to be of great use to discover basic molecular mechanisms and signaling pathways underlying evolutionarily conserved biological processes. However, the identification of new protein interactions implicated in signaling pathways can be particularly challenging in Dictyostelium due to its extremely fast signaling kinetics coupled with the dynamic nature of signaling protein interactions. Recently, the proximity labeling method using engineered ascorbic acid peroxidase 2 (APEX2) in mammalian cells was shown to allow the detection of weak and/or transient protein interactions and also to obtain spatial and temporal resolution. Here, we describe a protocol for successfully using the APEX2-proximity labeling method in Dictyostelium. Coupled with the identification of the labeled proteins by mass spectrometry, this method expands Dictyostelium's proteomics toolbox and should be widely useful for identifying interacting partners involved in a variety of biological processes in Dictyostelium.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis.

Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide and has a great socio-economic impact. Modified oxidative lipid metabolism and dysregulated iron homeostasis have been implicated in the pathogenesis of this disorder, but the detailed pathophysiological mechanisms still remain unclear. Apolipoprotein E (APOE) is a lipid-binding protein that occurs in large quantities in human blood plasma, and a polymorphism of the APOE gene locus has been identified as risk factors for AD. The human genome involves three major APOE alleles (APOE2, APOE3, APOE4), which encode for three subtly distinct apolipoprotein E isoforms (APOE2, APOE3, APOE4). The canonic function of these apolipoproteins is lipid transport in blood and brain, but APOE4 allele carriers have a much higher risk for AD. In fact, about 60% of clinically diagnosed AD patients carry at least one APOE4 allele in their genomes. Although the APOE4 protein has been implicated in pathophysiological key processes of AD, such as extracellular beta-amyloid (Aß) aggregation, mitochondrial dysfunction, neuroinflammation, formation of neurofibrillary tangles, modified oxidative lipid metabolism, and ferroptotic cell death, the underlying molecular mechanisms are still not well understood. As for all mammalian cells, iron plays a crucial role in neuronal functions and dysregulation of iron homeostasis has also been implicated in the pathogenesis of AD. Imbalances in iron homeostasis and impairment of the hydroperoxy lipid-reducing capacity induce cellular dysfunction leading to neuronal ferroptosis. In this review, we summarize the current knowledge on APOE4-related oxidative lipid metabolism and the potential role of ferroptosis in the pathogenesis of AD. Pharmacological interference with these processes might offer innovative strategies for therapeutic interventions.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Understanding the molecular crossroads in acute liver failure: A pathway to new therapies.

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

The Antioxidant Defense System of Tomato (Solanum lycopersicum L.) Varieties under Drought Stress and upon Post-Drought Rewatering.

Water shortage induces physiological, biochemical, and molecular alterations in plant leaves that play an essential role in plant adaptive response. The effects of drought and post-drought rewatering on the activity of antioxidant enzymes and levels of H2O2, phenolic compounds, ascorbic acid, and proline were studied in six local tomato (Solanum lycopersicum L.) varieties. The contents of H2O2 and ascorbic acid increased in all drought-exposed tomato plants and then decreased upon rewatering. The level of phenolic compounds also decreased in response to water shortage and then recovered upon rehydration, although the extent of this response was different in different varieties. The activities of ascorbate peroxidase (APX) and guaiacol peroxidase (POX) and the content of proline significantly increased in the drought-stressed plants and then decreased when the plants were rewatered. The activities of 8 constitutive APX isoforms and 2 constitutive POX isoforms varied upon exposure to drought and were observed after rewatering in all studied varieties. The information on the response of tomato plants to drought and subsequent rewatering is of great importance for screening and selection of drought-tolerant varieties, as well as for development of strategies for increasing plant productivity under adverse environmental conditions.

Design of a two functional permeable reactive barrier for synergistic enzymatic and microbial bioremediation of phenol-contaminated waters: laboratory column evaluation : Enzymatic and microbial bioremediation of phenol in a bilayer permeable reactive barrier.

The present study aimed to develop a system using a combination of enzymatic and microbial degradation techniques for removing phenol from contaminated water. In our prior research, the HRP enzyme extracted from horseradish roots was utilized within a core-shell microcapsule to reduce phenolic shock, serving as a monolayer column. To complete the phenol removal process, a second column containing degrading microorganisms was added to the last column in this research. Phenol-degrading bacteria were isolated from different microbial sources on a phenolic base medium. Additionally, encapsulated calcium peroxide nanoparticles were used to provide dissolved oxygen for the microbial population. Results showed that the both isolated strains, WC1 and CC1, were able to completely remove phenol from the contaminated influent water the range within 5 to 7 days, respectively. Molecular identification showed 99.8% similarity for WC1 isolate to Stenotrophomonas rizophila strain e-p10 and 99.9% similarity for CC1 isolate to Bacillus cereus strain IAM 12,605. The results also indicated that columns using activated sludge as a microbial source had the highest removal rate, with the microbial biofilm completely removing 100% of the 100 mg/L phenol concentration in contaminated influent water after 40 days. Finally, the concurrent use of core-shell microcapsules containing enzymes and capsules containing Stenotrophomonas sp. WC1 strain in two continuous column reactors was able to completely remove phenol from polluted water with a concentration of 500 mg/L for a period of 20 days. The results suggest that a combination of enzymatic and microbial degrading systems can be used as a new system to remove phenol from polluted streams with higher concentrations of phenol by eliminating the shock of phenol on the microbial population.

Colorimetric detection of neomycin sulfate in serum based on ultra-small gold nanoparticles with peroxidase-like activity.

Neomycin sulfate (NEO) is a kind of aminoglycoside antibiotics. Because of its strong ototoxicity, nephrotoxicity and other side effects, its content in the body should be strictly monitored during use. In this paper, a rapid colorimetric detection method for NEO based on ultrasmall polyvinylpyrrolidone modified gold nanoparticles (PVP/Au NPs) with peroxidase-like activity was developed. Firstly, ultra small PVP/Au NPs with weak peroxidase-like activity were synthetized. When they were mixed with NEO, strong hydrogen bonds were formed between NEO and PVP, resulting in the aggregation of PVP/Au NPs, and the aggregated PVP/Au NPs showed stronger peroxidase-like activity. Therefore, rapid colorimetric detection of NEO was achieved by utilizing the enhanced peroxidase-like activity mechanism caused by the aggregation of ultra small PVP/Au NPs. The naked eye detection limit of this method is 50 nM. Within the range of 1 nM-300 nM, there was a good linear relationship between NEO concentration and the change in absorbance intensity of PVP/Au NPs-H2O2-TMB solution at 652 nm, with the regression curve of y = 0.0045x + 0.0525 (R2 = 0.998), and the detection limit is 1 nM. In addition, this method was successfully applied to the detection of NEO in mouse serum. The recoveries were 104.4 % -107.6 % compared with HPLC assay results, indicating that this method for NEO detection based on PVP/Au NPs has great potential in actual detection of NEO in serum.

Heteroatom-doped cobalt single-atomic nanozymes with differential enzyme-like activity for bacteria-infected wound therapy.

Single-atom nanozymes (SANZs) have emerged as new media for enhancing chemodynamic therapy (CDT) to achieve desirable enzyme-like effects and excellent nanoscale specificity. However, non-optimal adsorption of Fenton-like reaction intermediates prevents SANZs from exerting kinetic activity and hinders the CDT effect. Herein, we demonstrate that heteroatom-doped Co single-atom nanozymes (SACNZs) with intrinsic charge transfer exhibit peroxidase-like properties and significantly improve the ability of CDT to treat Staphylococcus aureus-infected wounds. Density functional theory calculations showed that the S-induced charge transfer effect regulated the electronic distribution of the central metal more efficiently than P, thereby lowering the energy levels for the generation of OH and increasing the catalytic effect. Polyvinylpyrrolidone-modified SACNZs showed effects consistent with this theory in both in vitro antibacterial and in vivo ward management assays. This study systematically investigated the relationship between heteroatom-doping and the catalytic activity of metal centres, opening a new perspective for the application of CDT.

Acute Urticaria: Symptoms, Causes, and Evaluation of Phenotypes Prone to Chronicity.

INTRODUCTION: Urticaria is a condition that is characterized by the development of wheals (hives), angioedema, or both. If symptoms persist for less than 6 weeks, it is classified as acute urticaria (AU), and if they persist for longer than 6 weeks, it is classified as chronic urticaria (CU). Disease activity is evaluated using validated patient-reported outcome measures (PROMs) such as the 7-day urticaria activity score (UAS-7) and urticaria control test (UCT). In this study, we aimed to determine whether there was a difference between patients with chronic and recovered urticaria in terms of age, sex, symptoms, disease severity, disease control, and triggering factors by following patients with AU for 6 months. METHODS: The routine tests were requested at the first admission of the patients. If previously examined, anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody, etc., were recorded. After the first examination, the patients were evaluated again using a visual analog scale (VAS), UCT, UAS-7, and medication scores (MSs) in the 1st, 3rd, and 6th months. RESULTS: One hundred nine (F/M: 80/29) patients were included in the study. Twenty-seven patients had a previous history of AU, 22 of these patients were evaluated as having recurrent AU, and five became chronic during follow-up. Urticaria continued in 22 of 82 patients who presented with first-attack AU in the 3rd month and 17 in the 6th month. We had a chronicity rate of 24.7%. It was determined that having positive anti-TPO increased the risk of CU 1.69 times. A statistically significant improvement was found in the mean VAS, UCT, UAS-7, and MSs evaluated in the 1st, 3rd, and 6th months of patients with CU compared with baseline. CONCLUSION: AU is a common disease and usually heals in a short time without becoming chronic. Studies on the causes of chronicity are limited. Testing anti-TPO in patients presenting with AU may be useful in terms of disease course and risk of chronicity.

Thyroid auto-antibodies in newly diagnosed multiple sclerosis patients: A cross sectional study.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease in which the immune system attacks the myelin sheath of the central nervous system (CNS). It has been proposed that autoimmune conditions may occur together and an individual's immune system may attack more than one system. Autoimmune thyroid disease is one of the most common comorbidities along with MS. Since thyroid hormones are crucial for normal brain function and remyelination, we aimed to determine the prevalence of thyroid dysfunction in a group of MS patients compared with healthy controls. Methods: This cross-sectional study was conducted in medical clinics affiliated to Shiraz University of Medical Sciences, South of Iran. To prevent the effects of MS modifying drugs on thyroid function, we examined 73 newly diagnosed MS patients, which had not been treated yet, compared to 72 healthy individuals. Results: After measurement of the serum level of TSH, Anti TPO-Ab, and Anti TG-Ab, we found a significantly higher prevalence rate of abnormal TSH levels (high or low) in the MS group (p = 0.02). We also found a higher frequency of thyroid dysfunction in the female MS group (p = 0.01). However, there was no significant difference in the two other anti-thyroid antibodies among the groups. Our results demonstrate a significant and positive linear relationship between age and TSH levels (R = 0.402; p < 0.001) and also age and Anti TPO-Ab levels (R = 0.397; p < 0.001) among the MS population. Conclusion: We found a higher prevalence of TSH alteration among the MS population. Anti TPO-Ab and Anti TG-Ab levels did not differ among groups. These findings suggest that MS patients might be at an increased risk for thyroid dysfunction. However, further studies are required to determine the underlying cause. The linear relationship between age and TSH and Anti TPO-Ab levels in MS patients suggest that there is an association between TSH dysfunction and age.

Cu-promoted synthesis of triclosan-Mannich and Glaser adducts: anti-mycobacterial evaluation with in silico validations.

Aim: The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.1 million reported in 2020. The incidence rate of TB showed 3.6% rise from 2020 to 2021. Results/methodology: This manuscript discloses Cu-promoted single pot A3-coupling between triclosan (TCS)-based alkyne, formaldehyde and secondary amines to yield TCS-based Mannich adducts. Additionally, the coupling of TCS-alkynes in the presence of Cu(OAc)2 afforded the corresponding homodimers. Among tested compounds, the most potent one in the series 11 exhibited fourfold higher potency than rifabutin against drug-resistant Mycobacterium abscessus. The selectivity index was also substantially improved, being 26 (day 1) and 15 (day 3), which is four-times better than TCS.

[Box: see text].

Tailoring the peroxidase-like properties of Mo atom nanoclusters/N-MXene nanozymes for sensitive colorimetric detection of glutathione.

Although nanozyme engineering has made tremendous progress, there is a huge gap between them and natural enzymes due to the enormous challenge of precisely adjusting the geometric and electronic structure of active sites. Considering that intentionally adjusting the metal-carrier interactions may bring the promising catalytic activity, in this work, a novel Mo atom nanocluster is successfully synthesized using nitrogen-doped Mxene (MoACs/N-MXene) nanozymes as carriers. The constructed MoACs/N-MXene displays excellent peroxidase-like catalytic activity and kinetics, outweighing its N-MXene and Mo nanoparticles (NPs)-MXene references and natural horse radish peroxidase. This work not only reports a successful example of MoACs/N-MXene nanozyme as a guide for achieving peroxidase-mimic performance of nanozymes for colorimetric glutathione sensing at 0.29 µM, but also expands the application prospects of two-dimensional MXene nanosheets by reasonably introducing metal atomic clusters and nonmetal atom doping and exploring related nanozyme properties.

Catalase, Glutathione Peroxidase, and Peroxiredoxin 2 in Erythrocyte Cytosol and Membrane in Hereditary Spherocytosis, Sickle Cell Disease, and ß-Thalassemia.

Catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2) can counteract the deleterious effects of oxidative stress (OS). Their binding to the red blood cell (RBC) membrane has been reported in non-immune hemolytic anemias (NIHAs). Our aim was to evaluate the relationships between CAT, GPx, and Prx2, focusing on their role at the RBC membrane, in hereditary spherocytosis (HS), sickle cell disease (SCD), ß-thalassemia (ß-thal), and healthy individuals. The studies were performed in plasma and in the RBC cytosol and membrane, evaluating OS biomarkers and the enzymatic activities and/or the amounts of CAT, GPx, and Prx2. The binding of the enzymes to the membrane appears to be the primary protective mechanism against oxidative membrane injuries in healthy RBCs. In HS (unsplenectomized) and ß-thal, translocation from the cytosol to the membrane of CAT and Prx2, respectively, was observed, probably to counteract lipid peroxidation. RBCs from splenectomized HS patients showed the highest membrane-bound hemoglobin, CAT, and GPx amounts in the membrane. SCD patients presented the lowest amount of enzyme linkage, possibly due to structural changes induced by sickle hemoglobin. The OS-induced changes and antioxidant response were different between the studied NIHAs and may contribute to the different clinical patterns in these patients.

Resistance to death pathway induction as a potential targeted therapy in CRISPR/Cas-9 knock-out colorectal cancer cell lines.

Regulated cell death is a fundamental biological process that plays a crucial role in maintaining tissue homeostasis and eliminating damaged or unnecessary cells. Ferroptosis is an iron-dependent process, characterized by the accumulation of oxidized and damaged lipids, which leads to programmed cell death. Among the ferroptotic pathway genes regulating this process, GPX4, TFRC, ACSL4, FSP1, SLC7A11, and PROM2 could be considered. There are many well-known ferroptotic pathway regulators, which are discussed in this compact review. Cells with tissues of different origin display sensitive or resistant phenotypes to such regulators. In some cases, unexpected changes during cell treatment occurred, suggesting the possibility of regulating the death pathway. We assumed that possible changing of ferro-sensitivity to ferro-resistance in cells, especially in colorectal cancer cell lines, is responded for induced chemoresistance. Using novel techniques, such as CRISPR/Cas-9 genome editing, an induced phenotype "switching" is possible.