Search Results (120)

Murine double minute 2 (MDM2) is involved in various cancers and is an attractive target. The RING domain of MDM2 has been discussed as an alternative target to stabilize p53. Designing drugs to target the RING domain of MDM2 is an alternative approach to preventing MDM2-mediated deactivation of p53. In this study, we obtained a human VH single-domain antibody and revealed its regulatory effects and mechanisms. The RING domain of MDM2 was synthesized using a chemical synthesis method, and antibodies against the MDM2 RING domain were screened from a human VH single-domain antibody library and expressed intracellularly. A nuclear localization sequence was designed to ensure intrabody efficiency. The binding activity of the individually cloned antibodies was detected using ELISA. MTT and flow cytometry assays were used to detect the reactions related to intrabody in vitro. The combination and its influence on MDM2 were detected using immunoprecipitation assays, confocal microscopy, and Western blotting. The effects on apoptosis-related mitochondrial pathways downstream of p53 were examined using Western blotting. The influence on cell cycle distribution and cyclin-related proteins was detected using flow cytometry and Western blotting. A549 cell xenografts were constructed to assess the effect of intrabodies on growth in vivo. The molecular mechanisms of MDM2 and p53 were studied using Western blotting. Eight individual cloned antibodies were positive compared to the signals on the BSA-coated plates, especially intrabodies VH-HT3. In A549 and MCF-7 cell lines, VH-HT3 exhibited significant inhibitory effects on cell proliferation and apoptosis. VH-HT3 co-localized with MDM2 in the nucleus and cytoplasm. The specific combination of VH-HT3 triggered no significant effect on MDM2 activity for p53 degradation but upregulated the levels of factors downstream of p53, especially those in the mitochondrial apoptosis pathway. Moreover, VH-HT3 induced cell cycle arrest, and the expression of cyclin-related proteins was consistent with this observation. VH-HT3 also retarded the growth of A549 xenografts in vivo. Further tests suggested that VH-HT3 inhibited MDM2 function by increasing HIPK2 levels and activating p53 at the Ser46 site. VH-HT3, prepared from a human VH single-domain antibody library, inhibited p53 activity and produced a tumor-suppressive effect. The intrabody VH-HT3 is a candidate for the development of novel MDM2 inhibitors. Full article

Survivors of severe hypothermia frequently exhibit cognitive impairments. However, the underlying mechanisms remain inadequately understood. In order to reveal the scientific problem of cognitive dysfunction caused by severe hypothermia, providing an experimental basis for clinical treatment, this study utilized animal models and combined cognitive behavioral, morphological, and molecular biological experiments. The results showed that severe hypothermia leads to an accumulation of iron ions in the cerebral cortex tissue exceeding 70%, while increased Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression enhances sensitivity to ferroptosis. This process results in a nearly 50% decrease in glutathione (GSH) expression and over 50% degradation of glutathione peroxidase 4 (GPX4), leading to GPX4 deactivation and increased lipid peroxidation, which in turn nearly doubles the levels of oxidative products such as MDA and 4NHE. Notably, ferroptosis inhibition using Ferrostatin-1 (Fer-1) effectively mitigates the degenerative death of cerebral cortical neurons induced by severe hypothermia, significantly improving the associated cognitive deficits. These findings suggest that severe hypothermia may induce ferroptosis in cortical neurons through the Nrf2/SLC7A11/GSH/GPX4 signaling axis. Targeted inhibition of ferroptosis has the potential to be a promising therapeutic direction for the prevention and treatment of cognitive impairment caused by severe hypothermia. Full article

In this work, a sustainable approach to reclaiming high-value anatase/rutile TiO₂ nanoparticles from deactivated or used selective catalytic reduction (SCR) catalysts is demonstrated using a composite flux (NaOH/Na₂CO₃) through an efficient sintering and subsequent leaching methodology. This method directly addresses the urgent need for circular economy strategies in industrial waste management. Sintering experiments revealed that while NaOH enhanced the separation efficiency of V₂O₅ and SiO₂, it led to agglomerated products, hindering TiO₂ recovery. In contrast, Na₂CO₃ enabled the production of powdery sintered residues, facilitating the complete separation of anatase/rutile TiO₂ nanoparticles, as confirmed by XRD. By optimizing the sintering-leaching conditions, this method achieves near-total recovery of TiO₂ with retained photocatalytic performance, ensuring its suitability for reuse in applications such as air/water purification or renewable energy systems. This study advances sustainability by repurposing industrial waste into high-performance materials, reducing the energy and resource demands associated with conventional TiO₂ synthesis, and preventing hazardous material leakage into ecosystems. The scalable, low-complexity process aligns with global sustainability goals, including responsible consumption (SDG 12), climate action (SDG 13), and industrial innovation (SDG 9), offering a blueprint for transforming waste streams into valuable resources for a greener economy. Full article

Nanozymes, exemplified by metal nanoparticles, have shown promise in the fields of biological diagnostics and therapeutics. However, their practical application is often hindered by aggregation or deactivation in complex biological systems. Here, we develop a DNA-engineered nanozyme coating to preserve the peroxidase-like catalytic activity of platinum nanoparticles in complex biological environments. We employed thiol-modified single-stranded DNA to coat the platinum nanoparticles through metal–sulfur interaction. We found that the negatively charged DNA coating prevents the aggregation of platinum nanoparticles in high-salt environments. Moreover, the DNA coating functions as a molecular sieve, inhibiting non-specific protein adsorption while preserving substrate access to the catalytic interface, thus sustaining high peroxidase-like catalytic activity in serum. As a proof of concept, we demonstrate miRNA detection in serum samples with a detection limit of 1 fM. This approach offers a versatile strategy for molecular diagnostics of nanozymes in complex biological environments. Full article

A stabilized biochar (BC)–nano-scale zero-valent iron (nZVI) composite (BC-nZVI@Cell-g-PAA) was prepared using cellulose-grafted polyacrylic acid (Cell-g-PAA) as the raw material through in situ polymerization and liquid-phase reduction methods for the remediation of hexavalent chromium (Cr(VI))-contaminated water. BC-nZVI@Cell-g-PAA was characterized by XRD, FT-IR, SEM, BET, TEM, and XPS. According to the batch experiments, under optimized conditions (Cr(VI) concentration of 50 mg/L, pH = 3, and dosage of 2 g/L), the BC-nZVI@Cell-g-PAA composite achieved maximum Cr(VI) removal efficiency (99.69%) within 120 min. Notably, BC, as a carrier, achieved a high dispersion of nZVI through its porous structure, effectively preventing particle agglomeration and improving reaction activity. Simultaneously, the functional groups on the surface of Cell-g-PAA provided excellent protection for nZVI, significantly suppressing its oxidative deactivation. Furthermore, the composite effectively reduced Cr(VI) to insoluble trivalent chromium(Cr(III)) species and stabilized them on its surface through immobilization. The synergistic effects of physical adsorption and chemical reduction greatly contributed to the removal efficiency of Cr(VI). Remarkably, the composite exhibited excellent reusability with a removal efficiency of 62.4% after five cycles, demonstrating its potential as a promising material for remediating Cr(VI)-contaminated water. In conclusion, the BC-nZVI@Cell-g-PAA composite not only demonstrated remarkable efficiency in Cr(VI) removal but also showcased its potential for practical applications in environmental remediation, as evidenced by its sustained performance over multiple reuse cycles. Moreover, Cr(VI), a toxic and carcinogenic substance, poses significant risks to aquatic ecosystems and human health, underscoring the importance of developing effective methods for its removal from contaminated water. Full article

The increasing prevalence of the spectrum of Steatotic Liver Disease (SLD), including Metabolic-Associated Steatotic Liver Disease (MASLD), Metabolic-Associated Steatohepatitis (MASH), and progression to Cirrhosis and Hepatocellular Carcinoma (HCC) has led to intense research in disease pathophysiology, with many studies focusing on the role of iron. Iron overload, which is often observed in patients with SLD as a part of metabolic hyperferritinaemia (MHF), particularly in the reticuloendothelial system (RES), can exacerbate steatosis. This imbalance in iron distribution, coupled with a high-fat diet, can further promote the progression of SLD by means of oxidative stress triggering inflammation and activating hepatic stellate cells (HSCs), therefore leading to fibrosis and progression of simple steatosis to the more severe MASH. The influence of iron overload in disease progression has also been shown by the complex role of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. Ferroptosis depletes the liver’s antioxidant capacity, further contributing to the development of MASH, while its role in MASH-related HCC is potentially linked to alternations in the tumour microenvironment, as well as ferroptosis resistance. The iron-rich steatotic hepatic environment becomes prone to hepatocarcinogenesis by activation of several pro-carcinogenic mechanisms including epithelial-to-mesenchymal transition and deactivation of DNA damage repair. Biochemical markers of iron overload and deranged metabolism have been linked to all stages of SLD and its associated HCC in multiple patient cohorts of diverse genetic backgrounds, enhancing our daily clinical understanding of this interaction. Further understanding could lead to enhanced therapies for SLD management and prevention. Full article

Aflatoxins are foodborne toxins that occur naturally in various crops because of fungal contamination, particularly from two strains, namely Aspergillus flavus and Aspergillus parasiticus. Given their adverse properties, which are teratogenic, mutagenic, and carcinogenic, aflatoxins present a significant public health concern. Consequently, efforts are underway to inactivate aflatoxins and inhibit the growth of these fungi to prevent toxin formation. Since chemical treatments for food products are undesirable or even restricted in some countries, alternative approaches are also implemented. This study investigated gamma-ray (γ-ray) irradiation as a potential method for reducing aflatoxin levels. Specifically, solutions of aflatoxins B1, B2, G1, and G2 were irradiated with doses of 1, 2, 4, and 8 kGy using a cobalt-60 irradiation source. Following γ-irradiation, a notable reduction in aflatoxin levels was observed, particularly for types B1 and G1, which process higher toxicity. This finding suggests γ-irradiation as a feasible method for aflatoxin deactivation. Additionally, as a proof of concept, almond samples spiked with aflatoxins and A. flavus were irradiated. The results showed a decrease in both aflatoxin levels and microbial load in these samples. Overall, these findings indicate that γ-irradiation is a promising approach to aflatoxin reduction, microbial decontamination, and the potential extension of almonds’ shelf life. Full article

Electroporation ablation, as an innovative cancer treatment, not only preserves the structure and function of affected organs but also significantly reduces surgical risks, offers patients a safer and more effective therapeutic option, and demonstrates immense potential in the field of oncology. This paper presents the innovative design of a high-voltage nanosecond pulse generator triggered by a silicon carbide (SiC) photoconductive switch. The generator is capable of stably outputting adjustable voltages ranging from 10 kV to 15 kV, with pulse widths precisely controlled between 10 and 15 nanoseconds, and an operating frequency adjustable from 1 Hz to 10 Hz. This device enables instant activation and deactivation of the pulse generator during ablation, enhancing the efficiency of strong electric field applications and preventing overtreatment due to delayed shutdown. This paper introduces the structure and basic principles of this novel SiC photoconductive switch-triggered pulse device and reports on the impact of device-related pulse parameters on the ablation effect of hepatocellular carcinoma cells through cell experiments. Under optimal ablation parameters, the CCK8 results show that the number of viable cells is only 0.7% of that in the untreated control group after 12 h of subculture following ablation. These findings hold significant importance for expanding the application areas of SiC devices. Full article

The oxidative desulfurization (ODS) of heavy fuel oil (HFO) offers a promising solution for desulfurizing marine fuels under mild conditions, in line with current environmental regulations. While most studies focus on model or light fuels, explaining deactivation through leaching or sulfone adsorption, the deactivation mechanisms of catalysts in HFO remain poorly understood. In this work, Mo-based catalysts supported on alumina were extensively characterized before and after catalytic reactions, and regeneration through air calcination was considered. Techniques such as XRD, Raman spectroscopy, XRF, and TGA, alongside catalytic testing with H₂O₂ as an oxidant, revealed that Mo surface speciation significantly impacted both activity and deactivation. Contrary to well-dispersed polymolybdates, crystalline MoO₃ induced low activity and hindered regeneration. No leaching of the active phase was demonstrated during the reaction. Sulfone adsorption had minimal impact on deactivation, while non-sulphur compounds appeared to be the key contributors. Regeneration outcomes were found to be molybdenum content-dependent: 10Mo/Al recovered its activity, while 20Mo/Al formed inactive phases, like Al₂(MoO₄)₃. Using an organic oxidant (tBHP) during ODS influenced the regeneration, as it prevented Al₂(MoO₄)₃ formation and redispersed crystalline MoO₃, enhancing performance. These findings advance understanding of catalyst deactivation and suggest strategies to extend catalyst life in the ODS of HFO. Full article

The alkylation reaction of aromatic compounds gains considerable attention because of its wide application in bulk and fine chemical production. Aromatics alkylated with olefins is a well-known process, particularly for linear alkylbenzene, phenyloctanes, and heptyltoluene production. As octane boosters and precursors for various petrochemical and bulk chemical products, a wide range of alkylated compounds are in high demand. Numerous unique structures have been proposed in addition to the usual zeolites (Y and beta) utilized in alkylation procedures. The inevitable deactivation of industrial catalysts over time on stream, which is followed by a decrease in catalytic activity and product selectivity, is one of their disadvantages. Therefore, careful consideration of catalyst deactivation regarding the setup and functioning of the process of catalysis is necessary. Although a lot of work has been carried out to date to prevent coke and increase catalyst lifespan, deactivation of the catalyst is still unavoidable. Coke deposition can lead to catalyst deactivation in industrial catalytic processes by obstructing pores and/or covering acid sites. It is very desirable to regenerate inactive catalysts in order to remove the coke and restore catalytic activity at the same time. Depending on the kind of catalyst, the deactivation processes, and the regeneration settings, each regeneration approach has pros and cons. In this comprehensive study, the focus was on discussing the reaction mechanism of 1-octene isomerization and toluene alkylation as an example of isomerization and alkylation reactions that occur simultaneously, shedding light in detail on the catalysts used for this type of complex reaction, taking into account the challenges facing the catalyst deactivation and reactivation procedures. Full article

Can the foamability of surfactant aqueous solutions be controlled chemically? Well-known antifoams can prevent foaming by inducing the coalescence of the bubbles, but can the surfactants be deactivated chemically? If yes, how does this affect the surface tension of their aqueous solutions and their foaming capacity? To shed a light on these fundamental questions, we chose a well-known surfactant containing in its molecule a sulfate group (Sodium dodecyl sulfate, SDS) and mixed it with BaCl₂, (the solubility of BaSO₄ is 0.245 mg/100 mL water, T = 20 °C), Pb(NO₃)₂ (the solubility of PbSO₄ is 40.4 mg/100 mL water, T = 25 °C) and FeCl₃ (the solubility of Fe₂(SO₄)₃ is 25.6 g/100 mL water, T = 20 °C) at different molar ratios (MX_n/SDS): 1/2, 1/1, 2/1, 4/1. The results were surprising: in the case of BaCl₂, despite being in stoichiometric molar ratio with SDS (BaCl₂ + 2SDS -> Ba(DS)₂ + 2 NaCl), or in excess of BaCl₂, which should convert the whole amount of SDS into a sediment, the surface tension value remained significantly lower than that of the single surfactant. At the same time, foamability was either low or absent. It therefore appears that all of the surfactants should be converted into a sediment with very small solubility, but the low surface tension indicates the opposite. The lack of foamability indicated the opposite of that opposite. With Pb(NO₃)₂ and FeCl₃, the results are even stranger. The surface tension values are substantially smaller than those of the single surfactants, and at the same time, low foamability or lack of foamability was observed. It appears that the surfactant exists and at the same time does not exist in the aqueous solution. Where is the truth? Future studies will shed a light. Full article

Among the alkali metals, potassium is known to significantly shift selectivity toward value-added, heavier alkanes and olefins in iron-based Fischer–Tropsch synthesis catalysts. The aim of the present contribution is to shed light on the mechanism of action of alkaline promoters through a systematic study of the structure–reactivity relationships of a series of Fe oxide FTS catalysts promoted with Group I (Li, Na, K, Cs) alkali elements. Reactivity data are compared to structural data based on in situ, synchrotron-based XRD and XPS, as well as temperature-programmed studies (TPR-H₂, TPC-CO, TPD-CO₂, and TPD-H). It has been observed that the alkali elements induced higher carburization rates, higher basicities, and lower adsorbed hydrogen coverages. Catalyst stability followed the trend Na-Fe > unpromoted > Li-Fe > K-Fe > Cs-Fe, being consistent with the ability of the alkali (Na) to prevent active site loss by catalyst reoxidation. Potassium was the most active in promoting high α hydrocarbon formation. It is active enough to promote CO dissociative adsorption (and the formation of FeCx active phases) and decrease the surface coverage of H-adsorbed species, but it is not so active as to cause premature catalyst deactivation by the formation of a carbon layer resulting in the blocking active sites. Full article

The underlying cause of commutation failures in traditional line-commutated converter (LCC) high-voltage direct-current (HVDC) transmission technology lies in the sensitivity of the thyristor devices, which are prone to turning off, thereby restoring the forward circuit breaker capability. This paper presents a coordination strategy between a controllable line-commutated converter (CLCC) and a voltage-sourced converter (VSC) and delves into the fault characteristics specific to CLCC damage. Our research focuses on CLCC topology, where fully controlled devices are incorporated to manage the thyristor’s turn-off time, ensuring its successful deactivation. This approach serves as a fundamental preventative measure against commutation faults. Furthermore, we employ a coordination strategy between the VSC and the CLCC to enhance the recovery time efficiency of the AC system. This strategy is simulated and validated using PSCAD software, and the results confirm its effectiveness in fault tolerance and AC system recovery. Full article

Western culture has assigned an essential role to productive activity in defining our lives. In Locke’s and Hegel’s thought, we see the model that became dominant in modern political philosophy: that of conceiving the subject as a result of, and only possible within, the triad of work–property–subject. Nowadays, this has reached the level of shaping the meaning of living, and our entire existences seem to be subjected to a concept of lives-as-work. Combining anthropology and philosophy, this article seeks to rethink subjectivation beyond the process of work and appropriation, delving into worldviews different from those of the West. Specifically, we will focus on the Yanomami form of life, a non-stratified indigenous people living in the Brazilian Amazon. We will analyze how the Yanomami prevent the process of subjectification by the objectification of one’s own work through a sort of anti-work and anti-property apparatus. This is achieved through specific techniques of underproduction, which constitute another approach to work, as well as through a completely different way of conceiving subjectivity. Furthermore, the Yanomami’s view of all entities as subjects endowed with intentionality appears as de-ontologizing the subject position and deactivating the dyads of subject/object and own/common. The result is a worldview where, with everyone being subjects—humans and non-humans, living and dead, entities and things of nature—no one can be dominus of anyone. Full article

Mobile Edge Computing (MEC) is crucial for reducing latency by bringing computational resources closer to the network edge, thereby enhancing the quality of services (QoS). However, the broad deployment of cloudlets poses challenges in efficient network slicing, particularly when traffic distribution is uneven. Therefore, these challenges include managing diverse resource requirements across widely distributed cloudlets, minimizing resource conflicts and delays, and maintaining service quality amid fluctuating request rates. Addressing this requires intelligent strategies to predict request types (common or urgent), assess resource needs, and allocate resources efficiently. Emerging technologies like edge computing and 5G with network slicing can handle delay-sensitive IoT requests rapidly, but a robust mechanism for real-time resource and utility optimization remains necessary. To address these challenges, we designed an end-to-end network slicing approach that predicts common and urgent user requests through T distribution. We formulated our problem as a multi-agent Markov decision process (MDP) and introduced a multi-agent soft actor–critic (MAgSAC) algorithm. This algorithm prevents the wastage of scarce resources by intelligently activating and deactivating virtual network function (VNF) instances, thereby balancing the allocation process. Our approach aims to optimize overall utility, balancing trade-offs between revenue, energy consumption costs, and latency. We evaluated our method, MAgSAC, through simulations, comparing it with the following six benchmark schemes: MAA3C, SACT, DDPG, S2Vec, Random, and Greedy. The results demonstrate that our approach, MAgSAC, optimizes utility by 30%, minimizes energy consumption costs by 12.4%, and reduces execution time by 21.7% compared to the closest related multi-agent approach named MAA3C. Full article