Efficient enhancement of the antimicrobial activity of Chlamydomonas reinhardtii extract by transgene expression and molecular modification using ionizing radiation.

BACKGROUND: Ionizing radiation has been used for mutagenesis or material modification. The potential to use microalgae as a platform for antimicrobial production has been reported, but little work has been done to advance it beyond characterization to biotechnology. This study explored two different applications of ionizing radiation as a metabolic remodeler and a molecular modifier to enhance the antimicrobial activity of total protein and solvent extracts of Chlamydomonas reinhardtii cells. RESULTS: First, highly efficient transgenic C. reinhardtii strains expressing the plant-derived antimicrobial peptides, AtPR1 or AtTHI2.1, were developed using the radiation-inducible promoter, CrRPA70Ap. Low transgene expression was significantly improved through X-irradiation (12-50 Gy), with peak activity observed within 2 h. Protein extracts from these strains after X-irradiation showed enhanced antimicrobial activity against the prokaryotic bacterium, Pseudomonas syringae, and the eukaryotic fungus, Cryptococcus neoformans. In addition, X-irradiation (12 Gy) increased the growth and biomass of the transgenic strains. Second, C. reinhardtii cell extracts in ethanol were γ-irradiated (5-20 kGy), leading to molecular modifications and increased antimicrobial activity against the phytopathogenic bacteria, P. syringae and Burkholderia glumae, in a dose-dependent manner. These changes were associated with alterations in fatty acid composition. When both transgenic expression of antimicrobial peptides and molecular modification of bioactive substances were applied, the antimicrobial activity of C. reinhardtii cell extracts was further enhanced to some extent. CONCLUSION: Overall, these findings suggest that ionizing radiation can significantly enhance the antimicrobial potential of C. reinhardtii through efficient transgene expression and molecular modification of bioactive substances, making it a valuable source of natural antimicrobial agents. Ionizing radiation can act not only as a metabolic remodeler of transgene expression in microalgae but also as a molecular modifier of the bioactive substances.

A stochastic photo-responsive memristive neuron for an in-sensor visual system based on a restricted Boltzmann machine.

In-sensor computing has gained attention as a solution to overcome the von Neumann computing bottlenecks inherent in conventional sensory systems. This attention is due to the ability of sensor elements to directly extract meaningful information from external signals, thereby simplifying complex data. The advantage of in-sensor computing can be maximized with the sampling principle of a restricted Boltzmann machine (RBM) to extract significant features. In this study, a stochastic photo-responsive neuron is developed using a TiN/In-Ga-Zn-O/TiN optoelectronic memristor and an Ag/HfO2/Pt threshold-switching memristor, which can be configured as an input neuron in an in-sensor RBM. It demonstrates a sigmoidal switching probability depending on light intensity. The stochastic properties allow for the simultaneous exploration of various neuron states within the network, making identifying optimal features in complex images easier. Based on semi-empirical simulations, high recognition accuracies of 90.9% and 95.5% are achieved using handwritten digit and face image datasets, respectively. In addition, the in-sensor RBM effectively reconstructs abnormal face images, indicating that integrating in-sensor computing with probabilistic neural networks can lead to reliable and efficient image recognition under unpredictable real-world conditions.

Effects of Gamma Irradiation on Changes in Chemical Composition and Antioxidant Activity of Euphorbia maculata Callus.

In this study, we investigated the effects of gamma irradiation on the antioxidant activity and metabolite profiles of Euphorbia maculata calli (PC3012). Gamma irradiation at various doses (0, 0.05, 0.5, and 10 kGy) significantly enhanced the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS+) radical scavenging activities of the callus extracts of PC3012 in a dose-dependent manner. High-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) analyses revealed that irradiation increased the lysophospholipid content, although no new antioxidant compounds were formed. Furthermore, a PLS-DA analysis revealed evident metabolic differences between non-irradiated and irradiated samples, which were further verified by statistical validation. These findings suggest that gamma irradiation induces specific biochemical modifications that enhance the bioactive properties of PC3012 calli. This technology exhibits potential for utilization in the natural product and food sectors, particularly in the development of functional foods and nutraceuticals with improved health benefits.

Excimer-ultraviolet-lamp-assisted selective etching of single-layer graphene and its application in edge-contact devices.

Since the discovery of graphene and its remarkable properties, researchers have actively explored advanced graphene-patterning technologies. While the etching process is pivotal in shaping graphene channels, existing etching techniques have limitations such as low speed, high cost, residue contamination, and rough edges. Therefore, the development of facile and efficient etching methods is necessary. This study entailed the development of a novel technique for patterning graphene through dry etching, utilizing selective photochemical reactions precisely targeted at single-layer graphene (SLG) surfaces. This process is facilitated by an excimer ultraviolet lamp emitting light at a wavelength of 172 nm. The effectiveness of this technique in selectively removing SLG over large areas, leaving the few-layer graphene intact and clean, was confirmed by various spectroscopic analyses. Furthermore, we explored the application of this technique to device fabrication, revealing its potential to enhance the electrical properties of SLG-based devices. One-dimensional (1D) edge contacts fabricated using this method not only exhibited enhanced electrical transport characteristics compared to two-dimensional contact devices but also demonstrated enhanced efficiency in fabricating conventional 1D-contacted devices. This study addresses the demand for advanced technologies suitable for next-generation graphene devices, providing a promising and versatile graphene-patterning approach with broad applicability and high efficiency.

A study on the formative usability testing for modular powered wheelchair.

The increasing prevalence of mobility impairments underscores the urgent need for accessible and affordable mobility aids. To overcome the mobility limitations of people with disabilities, there is an increasing need for the development of lightweight and portable powered wheelchairs that can be easily loaded. This study aimed to perform an early health technology assessment and a formative usability evaluation on a modular (detachable) powered wheelchair. It aimed to gauge device satisfaction among users, pinpoint areas for improvement, and detect any unforeseen errors to inform future development. Engaging 16 participants, including powered wheelchair users, healthcare professionals, and caregivers, the research evaluated the wheelchair's functionality in various scenarios, emphasizing safety, effectiveness, and convenience. Statistical analyses of task performance and satisfaction surveys highlighted that, while powered wheelchair users successfully completed tasks focusing on driving and power control, healthcare professionals and caregivers encountered difficulties with the wheelchair's assembly and disassembly. Despite general positivity, the surveys indicated mixed satisfaction levels regarding safety, validity, and convenience, with specific issues related to frame durability, seat comfort, and control mechanisms. These findings suggest that refining the wheelchair's design and addressing user concerns could significantly enhance satisfaction and mobility services. Future efforts will include a thorough review of an advanced prototype and further satisfaction assessments.

We believe that our study makes a significant contribution to the literature by addressing a critical gap in the understanding of user-centric design and usability testing for powered wheelchairs.By emphasizing the importance of early assessments and incorporating user feedback into the development process, our research offers practical insights for creating more accessible and user-friendly mobility solutions.This contribution is particularly relevant in the context of advancing assistive technology and improving the quality of life for individuals with disabilities.

Mitigating polyethylene-mediated periprosthetic tissue inflammation through MEDSAH-grafting.

Periprosthetic tissue inflammation is a challenging complication arising in joint replacement surgeries, which is often caused by wear debris from polyethylene (PE) components. In this study, we examined the potential biological effects of grafting a [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) polymer onto the surface of PE through a solvent-evaporation technique. J774A.1 macrophage-like cells and primary cultured mouse osteoblasts were treated with PE powder with or without the MEDSAH coating. MEDSAH grafting on PE substantially reduced the expression of pro-inflammatory cytokines and other mediators in primary cultured mouse osteoblasts, but did not significantly impact macrophage-mediated inflammation. Our findings suggest that a MEDSAH coating on PE-based materials has potential utility in mitigating periprosthetic tissue inflammation and osteolysis and preventing aseptic loosening in total joint replacements. Further research, including large-scale clinical trials and biomechanical analyses, is needed to assess the long-term performance and clinical implications of MEDSAH-coated PE-based materials in total joint arthroplasty.

Atomically thin iridium nanosheets for oxygen evolution electrocatalysis.

2D nanostructures of noble metals hold great potential for developing efficient electrocatalysts due to their high atom efficiency associated with their large specific surface area and abundant active sites. Here, we introduce a one-pot solvothermal synthesis method that can enable the fabrication of freestanding atomically thin Ir nanosheets. The thermal decomposition of a complex of Ir and a long-chain amine, which could readily be formed with the assistance of a strong base, under CO flow conditions successfully yielded Ir nanosheets consisting of 2-4 atomic layers. The prepared Ir nanosheets showed prominent activity and stability toward oxygen evolution electrocatalysis in acidic conditions, which can be attributed to their ultrathin 2D structure.

Facile Lithium Densification Kinetics by Hyperporous/Hybrid Conductor for High-Energy-Density Lithium Metal Batteries.

Lithium metal anode (LMA) emerges as a promising candidate for lithium (Li)-based battery chemistries with high-energy-density. However, inhomogeneous charge distribution from the unbalanced ion/electron transport causes dendritic Li deposition, leading to "dead Li" and parasitic reactions, particularly at high Li utilization ratios (low negative/positive ratios in full cells). Herein, an innovative LMA structural model deploying a hyperporous/hybrid conductive architecture is proposed on single-walled carbon nanotube film (HCA/C), fabricated through a nonsolvent induced phase separation process. This design integrates ionic polymers with conductive carbon, offering a substantial improvement over traditional metal current collectors by reducing the weight of LMA and enabling high-energy-density batteries. The HCA/C promotes uniform lithium deposition even under rapid charging (up to 5 mA cm-2) owing to its efficient mixed ion/electron conduction pathways. Thus, the HCA/C demonstrates stable cycling for 200 cycles with a low negative/positive ratio of 1.0 when paired with a LiNi0.8Co0.1Mn0.1O2 cathode (areal capacity of 5.0 mAh cm-2). Furthermore, a stacked pouch-type full cell using HCA/C realizes a high energy density of 344 Wh kg-1 cell/951 Wh L-1 cell based on the total mass of the cell, exceeding previously reported pouch-type full cells. This work paves the way for LMA development in high-energy-density Li metal batteries.

Bottom Deposition Enables Stable All-Solid-State Batteries with Ultrathin Lithium Metal Anode.

Modern strides in energy storage underscore the significance of all-solid-state batteries (ASSBs) predicated on solid electrolytes and lithium (Li) metal anodes in response to the demand for safer batteries. Nonetheless, ASSBs are often beleaguered by non-uniform Li deposition during cycling, leading to compromised cell performance from internal short circuits and hindered charge transfer. In this study, the concept of "bottom deposition" is introduced to stabilize metal deposition based on the lithiophilic current collector and a protective layer composed of a polymeric binder and carbon black. The bottom deposition, wherein Li plating ensues between the protective layer and the current collector, circumvents internal short circuits and facilitates uniform volumetric changes of Li. The prepared functional binder for the protective layer presents outstanding mechanical robustness and adhesive properties, which can withstand the volume expansion caused by metal growth. Furthermore, its excellent ion transfer properties promote uniform Li bottom deposition even under a current density of 6 mA·cm-2. Also, scanning electron microscopy analysis reveals a consistent plating/stripping morphology of Li after cycling. Consequently, the proposed system exhibits enhanced electrochemical performance when assessed within the ASSB framework, operating under a configuration marked by a high Li utilization rate reliant on an ultrathin Li.

Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage.

OBJECTIVE: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. METHODS: OA progression was examined in wild-type and Irf1-/- mice using histologic assessments and microcomputed tomography analysis of whole-joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase-accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ-H2AX foci and senescence-associated beta-galactosidase activity. RESULTS: Our genome-wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon-responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down-regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post-traumatic OA in mice. CONCLUSION: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.

Customised joystick-making and training service of power wheelchair using rapid prototyping in rehabilitation centre for people with cervical spinal cord injury: findings from two case studies.

PURPOSE: This study aimed to evaluate the clinical applicability of a customised power wheelchair joystick using rapid prototyping with 3D modeling and printing technology within a rehabilitation centre for patients with cervical spinal cord injury. MATERIALS AND METHODS: Two male participants with tetraplegia following cervical-level spinal cord injury who had difficulty operating a powered wheelchair were recruited. The procedure of the joystick-making and training service consists of four steps: (1) driving evaluation; (2) digital fabrication; (3) functional test; and (4) driving training. K-QUEST 2.0 (Korean-Quebec User Evaluation of Satisfaction version 2.0) was used to measure the usability of the off-the-shelf and customised joystick. RESULTS: During the application process, several redesign stages were required to obtain the final customised joystick. After participants attended a 30-min driving training five times per week for 8 weeks, the usability of the customised joystick was higher than that of the off-the-shelf one. CONCLUSION: Providing the customised joystick-making and training service can be used in hospitalised rehabilitation centre before the hospital discharge of patients and returns to their everyday lives.

3D printing technology in rehabilitation clinics can provide new benefits, including cost-effectiveness, customisation of assistive devices, higher productivity, and enhanced collaboration with clients. More specifically, the entire intervention process, from medical evaluation, designing and manufacturing the devices, and training the client, can be performed efficiently and quickly by rehabilitation practitioners who best understand the client's characteristics.This study aimed to confirm the clinical applicability of a quick and efficient service for a customised power wheelchair joystick using 3D modelling and printing technology in rehabilitation centres for patients with cervical spinal cord injury. This study is expected to provide clinical support for connecting potential users and practitioners with technological advancements.

Hunting for the vulnerability in chondrosarcoma by tracing metabolic and genetic links.

In this Backstory, we narrate our journey in establishing a multidisciplinary team for sarcoma research and uncovering vulnerabilities in chondrosarcoma cells associated with their NAD+ dependencies for survival.1 Our findings hold promise for exploitation, yielding a synergistic cytotoxic effect when combined with systemic therapy.

Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis.

Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD+) depletion, targeting the NAD+ synthesis pathway remains challenging due to broad implications in biological processes. Here, we establish SIRT1 as a central mediator reinforcing the dependency of chondrosarcoma cells on NAD+ metabolism via HIF-2α-mediated transcriptional reprogramming. SIRT1 knockdown abolishes aggressive phenotypes of chondrosarcomas in orthotopically transplanted tumors in mice. Chondrosarcoma cells thrive under glucose starvation by accumulating NAD+ and subsequently activating the SIRT1-HIF-2α axis. Decoupling this link via SIRT1 inhibition unleashes apoptosis and suppresses tumor progression in conjunction with chemotherapy. Unsupervised clustering analysis identifies a high-risk chondrosarcoma patient subgroup characterized by the upregulation of NAD+ biosynthesis genes. Finally, SIRT1 inhibition abolishes HIF-2α transcriptional activity and sensitizes chondrosarcoma cells to doxorubicin-induced cytotoxicity, irrespective of underlying pathways to accumulate intracellular NAD+. We provide system-level guidelines to develop therapeutic strategies for chondrosarcomas.

Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities.

Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

Simultaneous establishment of pancreatic cancer organoid and cancer-associated fibroblast using a single-pass endoscopic ultrasound-guided fine-needle biopsy specimen.

Considering the critical roles of cancer-associated fibroblasts (CAFs) in pancreatic cancer, recent studies have attempted to incorporate stromal elements into organoid models to recapitulate the tumor microenvironment. This study aimed to evaluate the feasibility of patient-derived organoid (PDO) and CAF cultures by using single-pass endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples from prospectively enrolled pancreatic cancer patients. The obtained samples were split into two portions for PDO and CAF cultures. PDOs and CAFs were cultured successfully in 54.4% (31/57) and 47.4% (27/57) of the cases, respectively. Both components were established in 21 cases (36.8%). Various clinicopathologic factors, including the tumor size, tumor location, clinical stage, histologic subtype, and tumor differentiation, did not influence the PDO establishment. Instead, the presence of necrosis in tumor samples was associated with initial PDO generation but no further propagation beyond passage 5 (P = 0.024). The "poorly cohesive cell carcinoma pattern" also negatively influenced the PDO establishment (P = 0.018). Higher stromal proportion in tumor samples was a decisive factor for successful CAF culture (P = 0.005). Our study demonstrated that the coestablishment of PDOs and CAFs is feasible even with a single-pass EUS-FNB sample, implying an expanding role of endoscopists in future precision medicine.

Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis.

AIMS: Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. MATERIALS AND METHODS: Human liver samples obtained from subjects with/without NASH were analyzed. For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). RESULTS: Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. CONCLUSIONS: This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH through autophagy activation mediated by inhibition of hepatocellular glucose uptake and consequently decreased intracellular O-GlcNAcylation.

A Modified Wet Transfer Method for Eliminating Interfacial Impurities in Graphene.

Graphene has immense potential as a material for electronic devices owing to its unique electrical properties. However, large-area graphene produced by chemical vapor deposition (CVD) must be transferred from the as-grown copper substrate to an arbitrary substrate for device fabrication. The conventional wet transfer technique, which uses FeCl3 as a Cu etchant, leaves microscale impurities from the substrate, and the etchant adheres to graphene, thereby degrading its electrical performance. To address this limitation, this study introduces a modified transfer process that utilizes a temporary UV-treated SiO2 substrate to adsorb impurities from graphene before transferring it onto the final substrate. Optical microscopy and Raman mapping confirmed the adhesion of impurities to the temporary substrate, leading to a clean graphene/substrate interface. The retransferred graphene shows a reduction in electron-hole asymmetry and sheet resistance compared to conventionally transferred graphene, as confirmed by the transmission line model (TLM) and Hall effect measurements (HEMs). These results indicate that only the substrate effects remain in action in the retransferred graphene, and most of the effects of the impurities are eliminated. Overall, the modified transfer process is a promising method for obtaining high-quality graphene suitable for industrial-scale utilization in electronic devices.

Application of ionizing radiation as an elicitor to enhance the growth and metabolic activities in Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii is a eukaryotic, unicellular photosynthetic organism and a potential algal platform for producing biomass and recombinant proteins for industrial use. Ionizing radiation is a potent genotoxic and mutagenic agent used for algal mutation breeding that induces various DNA damage and repair responses. In this study, however, we explored the counterintuitive bioeffects of ionizing radiation, such as X- and γ-rays, and its potential as an elicitor to facilitate batch or fed-batch cultivation of Chlamydomonas cells. A certain dose range of X- and γ-rays was shown to stimulate the growth and metabolite production of Chlamydomonas cells. X- or γ-irradiation with relatively low doses below 10 Gy substantially increased chlorophyll, protein, starch, and lipid content as well as growth and photosynthetic activity in Chlamydomonas cells without inducing apoptotic cell death. Transcriptome analysis demonstrated the radiation-induced changes in DNA damage response (DDR) and various metabolic pathways with the dose-dependent expression of some DDR genes, such as CrRPA30, CrFEN1, CrKU, CrRAD51, CrOASTL2, CrGST2, and CrRPA70A. However, the overall transcriptomic changes were not causally associated with growth stimulation and/or enhanced metabolic activities. Nevertheless, the radiation-induced growth stimulation was strongly enhanced by repetitive X-irradiation and/or subsequent cultivation with an inorganic carbon source, i.e., NaHCO3, but was significantly inhibited by treatment of ascorbic acid, a scavenger of reactive oxygen species (ROS). The optimal dose range of X-irradiation for growth stimulation differed by genotype and radiation sensitivity. Here, we suggest that ionizing radiation within a certain dose range determined by genotype-dependent radiation sensitivity could induce growth stimulation and enhance metabolic activities, including photosynthesis, chlorophyll, protein, starch, and lipid synthesis in Chlamydomonas cells via ROS signaling. The counterintuitive benefits of a genotoxic and abiotic stress factor, i.e., ionizing radiation, in a unicellular algal organism, i.e., Chlamydomonas, may be explained by epigenetic stress memory or priming effects associated with ROS-mediated metabolic remodeling.