Post-thaw quality of canine spermatozoa exposed to hydroxychalcones: a double-edged sword.

Intervening in the aberrant redox homeostasis of tumors, particularly toward reactive oxygen species (ROS) overload, holds considerable promise for cancer therapy, yet, is severely constrained by the robust compensatory antioxidant defense system (ADS) and the unavoidable disruption of redox homeostasis in normal tissues. Here, we present a catalytic redox-cycling nanoreactor, TEMPO radical-modified cross-linked lipoic acid nanoparticles (T@cLAN), designed to achieve robust oxidative stress amplification for cancer therapy. Lipoic acid (LA) characterized by a cyclic disulfide backbone enables intermolecular thiol-disulfide exchange to from GSH-responsive crosslinked networks, while enabling reversible interconversion with dihydrolipoic acid (DHLA), which can further participate in redox modulation. Mechanistically, T@cLAN depletes intracellular glutathione (GSH) and undergoes depolymerization to generate dihydrolipoic acid (DHLA), which actively participates in redox processes to enhance ROS production. TEMPO, functions as a catalyst rather than a stoichiometric scavenger, directly accelerating the endogenous LA/DHLA redox cycle, thereby further amplifying DHLA generation and sustaining both GSH depletion and ROS amplification. As validated by both in vitro and in vivo results, T@cLAN dismantles the major ADS barrier limiting tumor oxidative stress, achieving an overall 85% GSH depletion and elevating ROS levels by 37-fold compared to untreated tumor cells. Concurrently, it induces both apoptosis and ferroptosis, attaining a tumor inhibition rate of 80% while causing minimal impact on normal cells and tissues, underscoring its substantial potential for cancer therapy. STATEMENT OF SIGNIFICANCE: We engineer a nanoreactor (T@cLAN) as an innovative modality to address a central limitation of oxidative stress-mediated anticancer therapy, that is, the therapeutic attenuation imposed by the highly developed antioxidant defense machinery of tumor cells. T@cLAN is activated by intracellular glutathione, a key redox buffer, to engage two interlinked redox catalytic cycles, enabling sustained glutathione depletion and the amplified accumulation of cytotoxic reactive oxygen species. Through this cooperative redox reprogramming, T@cLAN promotes tumor cell apoptosis and ferroptosis, leading to pronounced anticancer activity. Notably, T@cLAN is activated within the tumor microenvironment while remaining largely quiescent in normal cells, reflecting an active and highly selective intervention mechanism that offers new directions for oxidative stress driven therapeutic innovation.

Nanoscale metal-organic frameworks regulate redox homeostasis for Cancer therapy.

Coordination-oxidation synergy in homogeneous advanced oxidation processes systems: The critical role of metal-pollutant complexation in redox modulation and process optimization

Mitochondria are morphologically and functionally heterogeneous and dynamically adapt to the current metabolic status of their hosting cell. Moreover, they are prominent sources but also sensitive targets of redox modulation and oxidative stress. Such subcellular ROS/redox signals are considered pivotal aspects in health and disease. Yet, their deciphering requires advanced optical tools. Here we took advantage of transgenic redox-indicator mice expressing a mitochondria-targeted reduction/oxidation-sensitive green fluorescent protein (roGFPm) in excitatory projection neurons. By excitation-ratiometric two-photon microscopy we quantified in acute brain slices the redox conditions of individual mitochondria. After developing adequate redox sensor calibrations and solving laser-mediated bleaching issues, we finally chose caudoputamen, which showed the most promising mitochondrial arrangement for our imaging approach. Confirming the reliability of single-mitochondria redox imaging, we characterized the interplay of redox state and mitochondrial morphology. In general, roGFPm was more oxidized in spherical than in filamentous mitochondria. Acute hypoxia reverted mitochondria to a more roundish shape and evoked a reducing shift. Furthermore, the fraction of spherical mitochondria increased with aging. Around postnatal day (pd)350, a significantly higher fraction of roundish mitochondria was present in females than in males. In addition, from pd150 on, female mice showed lower degrees of roGFPm oxidation than males. Both findings might be linked to estrogen levels, which decrease in female mice with reproductive senescence around pd350. In view of the pivotal role of mitochondria for cellular wellbeing and their involvement in various neuropathologies, the established single-organelle redox-imaging approach will foster further detailed studies.

Oxytocin is a nine-amino-acid peptide hormone renowned for its roles in reproduction and childbirth. Beyond these classical functions, it has attracted increasing research interest for its broader biological activities. Additionally, clinical studies have proposed oxytocin as a potential therapeutic agent for breast cancer, particularly triple-negative breast cancer, due to its ability to modulate cell proliferation and migration. Despite its wide recognition across various biological systems, the full scope of oxytocin's activity remains incompletely understood. Early studies have shown that metal ions can affect oxytocin's function. Building on this, our group previously demonstrated that oxytocin's redox state, regulated by its two cysteine residues, also modulates oxytocin-dependent signaling through Cu(II) and Zn(II) binding in HEK293T cells expressing the oxytocin receptor. In this study, we investigated the effects of metal-oxytocin preparations on triple-negative breast cancer cells (MDA-MB-231), focusing on cell migration and invasion. Our findings show that samples containing both oxytocin and copper (CuOT) differentially influence cellular behavior in a manner that depends on the redox state of oxytocin. Preparations combining Cu(II) with oxidized oxytocin (CuoxOT) promote cell invasion, while preparations combining Cu(II) with reduced oxytocin (CurOT) enhance migration. LC-MS analysis revealed that the cellular environment promotes partial reduction of oxOT and distinct structural rearrangements among CuOT species, suggesting dynamic redox modulation of OT in a tumor microenvironment. To assess the signaling mechanisms underlying these effects, we found that CuoxOT significantly downregulated PI3K and β-arrestin 2 expressions. These changes may support the distinct cellular responses observed with CuoxOT, particularly in relation to migration and invasion. This study highlights the potential of redox- and metal state-dependent oxytocin species as modulators of distinct signaling pathways in triple-negative breast cancer, offering new perspectives for targeted therapeutic strategies.

Constructing regulatory networks of Rubisco post-translational modifications: a novel avenue for engineering environment adaptive plants.

Ocular alkali burns are a severe ophthalmic emergency characterized by excessive production of reactive oxygen species (ROS), persistent inflammation, and corneal neovascularization, often resulting in visual impairment. We develop novel hybrid nanoparticles (CEL NPs) through coordination-driven self-assembly of Ce3+, ε-poly-L-lysine (EPL), and luteolin (Lut) to achieve synergistic ROS scavenging and anti-inflammatory effects. CEL NPs protect human corneal epithelial cells and macrophages from oxidative stress and apoptosis in vitro. CEL NPs also suppress inflammatory responses by inhibiting the NF-κB pathway while activating the Nrf2/HO-1 axis. They exhibit enhanced mucoadhesion and prolonged ocular retention in vivo. In a mouse model of alkali-induced corneal injury, topical CEL NPs markedly accelerate wound closure, reduce neovascularization, attenuate stromal edema, and decrease inflammatory cell infiltration. They outperform the individual components and match the efficacy of dexamethasone, without observable adverse effects. These results demonstrate a safe and effective nanotherapeutic strategy that combines dual redox modulation with anti-inflammatory mechanisms for treating ocular chemical injuries.

Spin crossover (SCO) describes the reversible interconversion between low-spin and high-spin electronic configurations in transition metal complexes, arising from a delicate balance between ligand field splitting and electron pairing energy. Cobalt-based extended metal atom chains (EMACs) and their heterometallic analogues, HEMACs, offer a versatile platform for probing spin-state energetics and switchable magnetism through variations in metal-metal and metal-ligand interactions. Here, we report the synthesis, redox chemistry, and magnetic properties of the heterometallic chains [CoPdCo(dpa)4Cl2] (1) and [CoNiCo(dpa)4Cl2] (2, dpa = 2,2'-dipyridylamido), together with their one-electron oxidized derivatives [1][SbCl6] and [2][PF6]. Variable-temperature single-crystal X-ray diffraction, SQUID magnetometry, variable-temperature 1H NMR spectroscopy, and density functional theory reveal that redox reaction and central metal substitution can modulate the spin-state equilibria of these Co-M-Co chains. The neutral complexes 1 and 2 feature antiferromagnetically coupled high-spin Co(II) termini, with 2 displaying structure-dependent spin crossover in the solid state. Upon oxidation, [1][SbCl6] adopts a robust high-spin configuration over the entire temperature range studied, whereas [2][PF6] undergoes an incomplete, temperature-driven spin crossover between low-spin and high-spin states, as evidenced by concerted structural, magnetic, and spectroscopic signatures. DFT calculations elucidate the delicate enthalpy-entropy balance governing these behaviors and highlight the role of central metal size and Co-N bond metrics in biasing the spin-state landscape. These results provide insight into the interplay between redox state, spin-state behavior, and heterometallic chain composition in cobalt-based HEMACs.

Circularly polarized light (CPL) provides a powerful optical degree of freedom for information encoding, yet most CPL-responsive systems rely on weak circular dichroism-based absorption and lack chemically amplified readout mechanisms. Here, we report a chirality-driven spin-photonic transduction platform in which CPL helicity is converted into polarization-dependent interfacial redox modulation within a chirality-induced spin selectivity (CISS)-consistent framework. A chiral plasmonic Au/Vo-CeO2 gate exhibits helicity-dependent hot-carrier dynamics and interfacial charge transfer, consistent with plasmonic spin orbit coupling related processes and CISS-related interfacial transport. The resulting helicity-dependent photovoltage response induces amplified electrochemical modulation of a PEDOT:PSS channel in an aqueous transistor. Meanwhile, dopamine oxidation at the chiral gate provides chemical amplification that strengthens polarization-dependent responses. The resulting system enables CPL discrimination in electrolyte and demonstrates polarization-controlled chemical transduction. As functional validation, the CPL-dopamine coupling enhances signal differentiation in pattern-recognition tasks and enables chemically gated, polarization-guided wing actuation, forming a compact perception-action loop. These results demonstrate a CISS-consistent spin-related interfacial transduction strategy for CPL detection and chemical signal amplification in chiral optoelectronic and spin-related interfacial systems.

PRDX4 expression potentially links redox adaptation to oncogenic signaling and tumor progression in pancreatic ductal adenocarcinoma.

Reparative macrophage polarization and macrophage-derived reactive oxygen species (ROS) are required for ischemia-induced revascularization in peripheral artery disease (PAD). Our previous study showed that mitochondrial fission protein dynamin-related protein 1 (DRP1) promotes reparative polarization and metabolic reprogramming in macrophages and post-ischemic neovascularization. However, the redox-dependent mechanism governing DRP1 activation in this context remains elusive. Here, using a mouse hindlimb ischemia (HLI) model of PAD, we identify cysteine sulfenylation (CysOH) of DRP1 as a critical redox modification induced in ischemic bone marrow (BM)-derived cells. BM chimeric mice reconstituted with CRISPR/Cas9-generated "redox-dead" DRP1-C631A knock-in mutant (Drp1C/A) BM exhibited markedly reduced limb perfusion recovery and CD31+ capillary density in ischemic muscles following HLI. These defects were associated with enhanced Ly6G+ neutrophil accumulation, pro-inflammatory F4/80+CD80+ M1-like macrophages and reduced anti-inflammatory F4/80+CD206+ M2-like macrophages in ischemic muscle. Mechanistically, using an in vitro PAD model, hypoxia serum starvation (HSS) rapidly induced NADPH oxidase 2-dependent cytosolic ROS production and DRP1-CysOH formation in wild-type macrophages. In contrast, Drp1C/A macrophages failed to undergo DRP1-CysOH-dependent mitochondrial fission under HSS, resulting in aberrant metabolic reprogramming characterized by enhanced glycolysis and mitochondrial ROS, pro-inflammatory p-NF-κB and M1-genes, and suppressed anti-inflammatory p-AMPK, efferocytosis and M2-genes. Thus, our findings establish DRP1 sulfenylation as a previously unrecognized redox-sensing mechanism that links ischemia-induced ROS to reparative macrophage reprogramming and revascularization, identifying a novel therapeutic target for PAD.

This study evaluated the effects of a phytogenic-based liquid anti-mycotoxin agent (grape and olive extracts) on the redox status, health, and performance of broilers. The experimental broilers were divided into two groups: (a) group C (control group) with 22,950 broilers and (b) group T (treatment group) with 23,256 broilers, including administration of 500 mL/ton of the tested agent in drinking water on the 9th-11th, and on the 23rd-25th and 31st-33rd day. A liquid chromatography tandem mass spectrometry with a quadrupole time of flight analyzer was performed with fungal metabolites on liver samples. Thiobarbituric acid reactive substances (TBARSs), protein carbonyls (CARBs), total antioxidant capacity (TAC), total protein, and liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) were determined in plasma. The relative abundance of the tenuazonic acid (TeA) was calculated for both groups, showing that the exposure of TeA was 83% lower in group T. TBARS and CARBs, as well as the levels of liver enzymes and total proteins, were significantly reduced, while TAC was increased in group T. No differences in mortality rate and a potential improvement in the growth performance of group T were noticed. In conclusion, administering a phytogenic-based liquid anti-mycotoxin agent to broiler positively affects redox status and mycotoxin management.

BackgroundCoronary angiography induces oxidative stress through contrast media exposure and ionizing radiation, potentially contributing to vascular and renal injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert antioxidant and anti-inflammatory effects beyond glycemic control. We investigated whether a single pre-procedural dose of empagliflozin modulates oxidative stress and inflammatory glycosylation patterns in non-diabetic patients undergoing elective coronary angiography.MethodsIn this prospective, randomized, double-blind study, 60 patients undergoing elective coronary angiography were assigned to standard care or empagliflozin 10 mg administered 2 h before the procedure. Blood samples were collected at baseline, 4 h, and 24 h post-procedure. Total antioxidant capacity (TAC), oxidative DNA damage (alkaline comet assay), and N-glycosylation profiles of immunoglobulin G (IgG) and total plasma proteins were analyzed. Longitudinal changes were assessed using mixed-effects models with correction for multiple testing.ResultsBaseline characteristics and procedural variables were comparable between groups. Empagliflozin administration was associated with attenuation of oxidative DNA damage 24 h after angiography and stabilization of antioxidant capacity compared with standard care. Directional shifts in IgG N-glycosylation toward a less pro-inflammatory profile were observed in the intervention group, including reduced agalactosylated and core-fucosylated glycans and relative preservation of galactosylated structures. Similar modulatory trends were detected in total plasma protein glycosylation patterns. Although several glycomic changes did not reach statistical significance after correction for multiple testing, the overall biological signal consistently favored reduced oxidative and inflammatory activation in the empagliflozin group.ConclusionsA single pre-procedural dose of empagliflozin was associated with attenuation of oxidative stress-related DNA damage and modulation of inflammatory glycosylation patterns following coronary angiography. These findings suggest a potential peri-procedural cytoprotective role of SGLT2 inhibition that warrants confirmation in larger studies.Trial registrationISRCTN11022820. Registered 13 October 2025. Retrospectively registered.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s40842-026-00304-5.

Vocal fold (VF) injury, frequently caused by laryngeal microsurgery, leads to fibrosis and phonation impairment. Effective therapies remain limited, partly due to limited understanding of VF injury mechanisms. Using single-cell RNA sequencing of injured human VFs, we identified marked oxidative stress upregulation in epithelial cells, highlighting the need for epithelial protection and redox modulation. Informed by this insight, we developed an in situ-forming redox-regulated hydrogel, compatible with endoscopic spray delivery. It forms a conformal gel on the VF surface within 2 seconds, providing physical shielding and oxidative microenvironment regulation. The hydrogel reduced intracellularandmitochondrial reactive oxygen species, activated endogenous protective mechanisms, preserved mitochondrial function, and consequently rescued epithelial cells from oxidative stress-induced apoptosis and proliferation loss. In vivo, the hydrogel accelerated epithelialization and restored functions (vibratory and phonatory). Overall, this study introduces a unique approach for functional VF repair and offers a promising paradigm for biomaterial development guided by pathological microenvironment.

Metastatic breast cancer (MBC) remains the leading cause of breast cancer-related mortality, driven by the ability of disseminated tumor cells to survive a series of intrinsically lethal stresses encountered during systemic progression, including loss of extracellular matrix attachment, oxidative damage, and immune-mediated cytotoxicity. While resistance to apoptosis has long been considered central to tumorigenesis, it is now evident that metastatic competence depends on coordinated modulation of multiple regulated cell death (RCD) pathways, notably anoikis, necroptosis, and ferroptosis. In this review, we synthesize current mechanistic and translational evidence describing how breast cancer cells reprogram these pathways across the metastatic cascade. We first delineate the molecular basis of anoikis and the adaptive mechanisms that enable anchorage-independent survival. We then examine how circulating tumor cells withstand oxidative and inflammatory stress through redox adaptation and modulation of necroptotic signaling. Within distant organ niches, microenvironmental factors-including metabolic constraints, inflammatory cues, and iron availability-govern susceptibility to ferroptosis and necroptosis, thereby influencing dormancy and metastatic outgrowth. We further introduce the concept of cell death plasticity, defined as the dynamic and context-dependent capacity of tumor cells to modulate, switch between, or simultaneously regulate multiple RCD pathways in response to microenvironmental and therapeutic pressures. This adaptive property underlies both metastatic persistence and therapy resistance, while simultaneously generating context-specific vulnerabilities. Finally, we critically evaluate emerging therapeutic strategies and biomarker frameworks aimed at exploiting these vulnerabilities. Despite strong preclinical rationale, clinical translation remains limited, underscoring the need for biomarker-driven and combinatorial approaches. Collectively, understanding the dynamic interplay among RCD pathways provides a conceptual and translational foundation for targeting metastatic and treatment-resistant breast cancer.

ABSTRACTAgeing is characterised by the accumulation of senescent cells. Owing to their irreversible cell‐cycle arrest, these cells lack the capacity to replenish the stem cell pool and regenerate tissue, while their pro‐inflammatory secretome propagates senescence in a paracrine manner. Much of the senescent phenotype has been attributed to dysregulated mTORC1 signalling, a key regulator of protein synthesis implicated in organismal ageing. Nonetheless, the mechanism underlying this dysregulation is poorly understood and limited to a few selected cell types. Here, we show that mTORC1 dysregulation is also a characteristic of senescent muscle precursor cells, and in contrast to reports in other cell types, senescent myoblasts do not rely on lysosomal nutrient liberation to sustain mTORC1 activity. Instead, they appear to depend on the PI3K/Akt pathway, which is upregulated in these cells. Exogenous antioxidants were identified to alleviate PI3K/Akt/mTORC1 signalling, while exogenous ROS has the capacity to activate mTORC1, supporting a model in which ROS acts upstream of this pathway in senescent myoblasts. Moreover, antioxidants were able to suppress the expression of pro‐inflammatory cytokines and enhance the differentiation of senescent myoblasts. Interestingly, prolonged antioxidant treatment led to increased cell death in senescent but not proliferating myoblasts, suggesting they are more prone to reductive stress‐induced cell death. We propose that, in vitro, the antioxidant capacity of many plant‐based compounds may underlie their reported benefits as therapeutics targeting senescent cells (senotherapeutics). Together, our findings provide novel insights into mTORC1‐dependent regulation of the senescent phenotype and highlight the role of redox modulation in senotherapeutic strategies.

A supramolecular MgTA@MnO₂ nanozyme platform supports human spinal cord organoid structural integration and locomotor recovery via microenvironmental reprogramming.

Myo-inositol in assisted reproductive technologies: Roles in sperm function, oocyte maturation, and embryo development across species.

Bridging oxidative post-translational modifications to biological meaning.