Inspired by the antifouling properties of shark skin and the bioadhesion of mussels, our study presents a three-layer biomimetic wound dressing with hierarchical wettability and rapid exudate drainage capabilities. The shark skin-inspired hydrophobic modified polyurethane (PU) sponge provides antifouling properties and serves as a bacterial barrier. The mussel-inspired dopamine-functionalized carboxymethyl chitosan hydrogel (CMCS-DOP) absorbs exudates and forms an in situ hydrogel, effectively capturing and eliminating bacteria. The porous sponge layer in direct contact with the wound facilitates rapid exudate drainage, preventing excessive wound hydration. This hierarchical structure coordinates exudate transport and bacterial removal. The fabricated PCD hydrogel sponge dressing (PCD dressing) exhibits a wettability transition (contact angle: 3°-35°-101°) and a water vapor transmission rate of 1021-797-691 g/m2. It demonstrates potent bactericidal effects against Staphylococcus aureus and Escherichia coli, with survival rates of only 13 % and 14 %, respectively, and bacterial-blocking efficiencies of 89 % and 94 %. In a chronic bacterial infection wound model, the PCD dressing outperforms conventional clinical dressings, increasing the wound healing rate by 25.8 %, reducing inflammation, and enhancing angiogenesis and collagen deposition. Notably, the PCD mitigates oxidative stress at the wound site by regulating the polarization of anti-inflammatory macrophages. This exudate-draining and responsive dressing offers a promising strategy for promoting the healing of wounds with high exudate levels.

Harnessing the redox potential of biochar to activate airborne O2 for contaminant removal is challenging. In this study, ferrihydrite (Fh) modified the boron (B), nitrogen (N) co-doped biochars (BCs) composites (Fh/B(n)NC) were developed for enhancing the degradation of a model pollutant, tetracycline (TC), merely by airborne O2. Fh/B(3)NC showed excellent O2 activation activity for efficient TC degradation with a apparent TC degradation rate of 5.54, 6.88, and 22.15 times that of B(3)NC, Fh, and raw BCs, respectively, where 1O2 and H2O2 were identified as the dominant ROS for TC degradation. The B incorporation into the carbon lattice of Fh/B(3)NC promoted the generation of electron donors, sp2 C and the reductive B species, hence boosting Fe(III) reduction and 1O2 generation. O2 adsorption was enhanced due to the positively charged adsorption sites (C-B+and NC+). And 1O2 was generated via Fe(II) catalyzed low-efficient successive one-electron transfer (O2 → O2·- → 1O2, H2O2), as well as biochar catalyzed high-efficient two-electron transfer (O2 → H2O2 → 1O2) that does not involve .O2- as the intermediate. Moreover, Fh/B, N co-doped biochar showed a wide pH range, remarkable anti-interference capabilities, and effective detoxification. These findings shed new light on the development of environmentally benign BCs materials capable of degradading organic pollutants.

The nano-based therapeutics to induce cellular oxidative damage is considered promising in cancer treatment. Photodynamic therapy (PDT) is a primary antitumor oxidative damage treatment method. However, the hypoxic environment of tumor tissues and the short lifetime of singlet oxygen significantly hampers PDT efficacy. Fortunately, nitric oxide (NO), as a form of gas therapy, can generate more toxic oxidative peroxynitrite ions (ONOO-) with hydrogen peroxide (H2O2), which significantly enhance the efficacy of PDT. In this context, we fabricated a thermally controlled reactive oxygen nanobombs CaO2@LA-ICG@TD (CAI@TD), which can release many reactive oxygen species (ROS) to enhance the synergistic anticancer efficiency under a. The cellular studies revealed that CAI@TD could produce oxygen and H2O2 to heighten the efficacy of PDT and NO and induce necrotic-apoptosis of MDA-MB-231 cells by mitochondria damage, lipid peroxidation, and DNA fragments. Moreover, CAI@TD with 808 nm laser irradiation achieved a significant inhibition on the xenograft tumor growth. This work provides an efficient strategy to produce a high amount of ROS for synergistic anticancer therapy, offering a ray of hope in the fight against cancer.

Peptide deformylase (PDF) is an essential bacterial enzyme involved in first step of N-methionine excision (NME) pathway during bacterial protein synthesis. In first step of NME, N-formyl group of nascent polypeptide chains is removed by PDF. PDF is a metallo-protease where metal cofactor is co-ordinated to a Cys and two His residues. We cloned and expressed this iron containing metallo-protease from Salmonella typhimurium (sPDF). We characterized the sPDF which is a mononuclear iron containing enzyme that displayed optimal in vitro activity in the presence of oxidation preventing agent like catalase. To have an insight into the role of metal ion in catalase dependent enzyme activity, we generated surrogate sPDF-Ni2+ and sPDF-Co2+. Interestingly, these proteins also showed catalase requirement for optimum enzyme activity. Thus our results argue the presence of the target (amino acid) of oxidation in the protein itself that might be crucial for the activity of the enzyme. To ascertain this aspect, we examined the oxidation status of active site cysteine of sPDF by mass spectrometry. Our results indicated that the direct oxidation/over-oxidation of active site cysteine is responsible for inactivation of sPDF protein. Furthermore, a comparison of PDF sequences from Gram-negative bacteria revealed the presence of this cysteine throughout the lineage. Thus, our results per se are indicative of a similar behaviour of all these Gram-negative peptide deformylase proteins.

Redox-based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs and probes of high specificity. In the context of anti-ferroptosis research for neurological diseases, the inaccessibility of a blood-brain barrier (BBB) permeable small molecular ferroptosis inhibitor, and the lack of specific ferroptosis probes, seriously impeded a deeper understanding of the mechanism of ferroptosis and the development of clinically applicable drugs. We report herein a novel 1,3,4-thiadiazole-functionalized druglike ferrostatin analogue entitled Ferfluor-1 with superior anti-ferroptosis potency, favorable BBB permeability and in vivo activity against stroke and Parkinson's disease. Moreover, the exclusive pseudo-excited-state intramolecular proton-transfer (ESIPT) property of Ferfluor-1 via a long-distance hydrogen-bonding network makes it the first sensitive ratiometric photoluminescent probe to detect phospholipid hydroperoxides and a specific indicator for the fluctuation of ferroptosis. These unprecedented advantages not only make Ferfluor-1 a potential tool for ferroptosis-related diagnostic and therapeutic applications in the central nervous system, but also pave the way to developing new theragnostic agents for precision redox detection and regulation.

Selective inhibition of TrxR1 over TrxR2 is a highly sought-after goal, because the two enzymes play distinct roles in cancer progression. However, achieving targeted inhibition is challenging due to their high homology and identical active site sequence. Herein we report a new subcellular photocatalysis approach for targeted inhibition by controllably activating organogold(I) prodrugs within the cytosol, the exclusive location of TrxR1. The NHC-Au(I)-alkynyl complexes are stable and evenly distributed in the cell; they can meanwhile be efficiently transformed into active NHC-Au(I)-L species (L = labile ligands) via a radical mechanism by photocatalysts released into the cytosol (from endosome/lysosome) upon light irradiation, leading to selective inhibition of TrxR1 without affecting TrxR2. This results in strong cytotoxicity to cancer cells with much higher selectivity than auranofin, a pan TrxR inhibitor that cannot discriminate TrxR1/2, along with potent antitumor activities in multiple zebrafish and mouse models. This subcellular prodrug activation may thus suggest a novel approach to precision targeting using the remarkable spatial control of photocatalysis.

The extensive use of cadmium sulfide nanoparticles (CdS-NPs), along with their natural formation through the complex biogeochemical transformation of anthropogenic cadmium ions (Cd2+), poses substantial risks to ecosystems and human health. Despite this, the mechanisms underlying the toxicity of CdS-NPs remain unclear. A key question is whether their toxicity arises from the nanoparticulate form of cadmium (Cd) or from the release of Cd2+. To explore this, we exposed freshwater clams (Corbicula fluminea) to environmentally relevant concentrations (0.01-1 mg/L) of CdS-NPs or Cd2+ for 10 days. Hematoxylin and eosin (HE) staining revealed significant damage to the digestive gland in both cases. Although CdS-NPs released some Cd2+ (≤10.4%), transcriptomic and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses indicated different toxicity mechanisms. CdS-NPs primarily induce ferroptosis, triggered by lysosomal dysfunction that releases Fe2+ into the cytoplasm, disrupting the cellular iron metabolism. In contrast, Cd2+ primarily induces an autophagic response, as evidenced by the upregulation of autophagy-related markers and activation of apoptosis pathways linked to mitochondrial membrane permeabilization. Overall, our findings suggest that the toxicity of CdS-NPs is not solely derived from Cd2+, highlighting the need to evaluate the risks posed by metal sulfide nanoparticles to benthic ecosystems.

Does putrescine (PUT) improve oocytes from reproductively old mice by promoting mitochondrial autophagy?

Germinal vesicle stage cumulus-oocyte complexes (COCs) were obtained from 9-month old female C57BL/6N mice and divided into control, PUT and difluoromethylornithine, inhibitor (DFMO) groups. These germinal vesicle COCs underwent mouse in-vitro maturation (IVM) culture to observe the extrusion of the first polar body in each group. Using JC-1, dichloro-dihydro-fluorescein diacetate fluorescent probes and a confocal microscope, the mitochondrial membrane potential integrity and reactive oxygen species levels were measured in metaphase II stage oocytes. The expression and cellular localization of the p53 protein were examined by immunofluorescence. Reverse transcription quantitative polymerase chain reaction was used to detect the activation of mitochondrial autophagy pathways. The potential mechanisms through which PUT improves oocytes from reproductively old mice were explored by single-cell transcriptomic analysis. Autophagosomes, autolysosomes and mitochondria in different groups were directly observed using transmission electron microscopy.

The addition of exogenous PUT can promote IVM of oocytes from reproductively old mice. It reduces oxidative stress by promoting the autophagy of damaged mitochondria, decreasing the levels of reactive oxygen species and increasing mitochondrial membrane potential. It affects the expression and subcellular localization of the p53 protein, and increases the expression of transcription factor EB, which may be the potential mechanism behind its promotion of autophagy.

The target and regulatory pathway of PUT in oocytes was clarified. Putrescine is an effective small molecule compound with significant potential for non-invasively improving the fertility of elderly women.

In this study, we investigated the protective effect of JBP485 against aristolochic acid I (AAI)-induced nephrotoxicity and explored the pharmacokinetic mechanisms. The effects of JBP485 on AAI-induced cytotoxicity and nephrotoxicity were evaluated in vitro and in vivo, respectively.

To ascertain the protective effect of JBP485 against AAI-induced nephrotoxicity, we measured levels of urea nitrogen (BUN), creatinine (CRE), and indoxol sulfate in blood and urine; determined kidney weight-to-body weight ratio; and performed hematoxylin and eosin (H&E) staining. Cell viability and Western blotting assays, along with determination of malondialdehyde (MDA), superoxide dismutase (SOD), and intracellular reactive oxygen species (ROS) contents, were carried out to explore mechanisms underlying the protective effects of JBP485 against AAI-induced nephrotoxicity.

JBP485 treatment attenuated AAI-induced injuries in rat kidney while decreasing the levels of indoxyl sulfate, CRE, and BUN in plasma and increasing those of indoxyl sulfate in urine compared to that in AAI alone-treated group. The co-administration of JBP485 with AAI significantly increased the concentration and AUC of AAI in plasma, while decreasing its cumulative urinary excretion and renal clearance. Moreover, JBP485 reduced the uptake of AAI in kidney slices and human organic anion transporter 1/3 (hOAT1/3)-transfected human embryonic kidney 293 (HEK293) cells, suggesting that JBP485 ameliorated AAI-induced nephrotoxicity by reducing renal exposure to AAI via OAT inhibition. Meanwhile, JBP485 modulated the abnormal expressions of Oat1, Oat3, organic cation transporter 2 (Oct2), P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (Mrp2) and multidrug and toxin extrusion proteins 1 (Mate 1) in rat kidney, suggesting that JBP485 improved tubular secretion in AAI-treated rats. Moreover, JBP485 reversed the AAI-induced changes in the expression of heme oxygenase 1 (HO-1), NAD(P) H: quinone oxidoreductase-1 (NQO1), B-cell lymphoma-2 (Bcl-2) protein expressions and Bcl-2-like protein 4 (Bax) induced by AAI in rat kidney. JBP485 increased cell viability and reduced intracellular levels of ROS in NRK-52E cells treated with AAI.

These results suggested that JBP485 protected against AAI-induced renal oxidative stress. All results indicated that JBP485 protected against AAI-induced nephrotoxicity by reducing renal exposure to AAI and alleviating oxidative stress. Our findings suggested that JBP485 has potential as a renoprotective agent for the prevention of AAI-induced nephrotoxicity.

Monitoring H2O2 dynamics in conjunction with key biological interactants is critical for elucidating the physiological outcome of cellular redox regulation. Optogenetic hydrogen peroxide sensor with HaloTag with JF635 (oROS-HT635) allows fast and sensitive chemigenetic far-red H2O2 imaging while overcoming drawbacks of existing red fluorescent H2O2 indicators, including oxygen dependency, high pH sensitivity, photoartifacts and intracellular aggregation. The compatibility of oROS-HT635 with blue-green-shifted optical tools allows versatile optogenetic dissection of redox biology. In addition, targeted expression of oROS-HT635 and multiplexed H2O2 imaging enables spatially resolved imaging of H2O2 targeting the plasma membrane and neighboring cells. Here we present multiplexed use cases of oROS-HT635 with other green fluorescence reporters by capturing acute and real-time changes in H2O2 with intracellular redox potential and Ca2+ levels in response to auranofin, an inhibitor of antioxidative enzymes, via dual-color imaging. oROS-HT635 enables detailed insights into intricate intracellular and intercellular H2O2 dynamics, along with their interactants, through spatially resolved, far-red H2O2 imaging in real time.

As a significant reactive oxygen species (ROS), ClO- plays versatile roles in daily life and many biological events. However, its abnormal levels are responsible for serious harm to human health. Therefore, it is of crucial interest to develop effective methods for detecting ClO- in foods and living organisms. In this work, a novel fluorescent probe ethyl 2-(3-formyl-2-methoxy-10H-phenothiazin-10-yl)acetate (PEA) for detecting ClO- was presented. It shows the merits of rapid ratiometric response (within 10 s), high selectivity and very large Stokes shift (190 nm). The detection limit of PEA for ClO- was determined to be 0.47 μM. We not only successfully prepared paper test strips for efficient qualitative naked eye ClO- detection, but also demonstrated its potential for the valid detection of ClO- in natural water samples, beverages and foods. Furthermore, the probe PEA was also applied to the fluorescence imaging of ClO- in onion epidermal cells.

Cysteine sulfenic acid (SOH) modifications are pivotal in redox signaling, yet establishing their causal biological roles remains challenging due to methodological limitations. Traditional approaches often lack precision or disrupt non-redox cysteine functions. This perspective highlights two innovative chemical biology strategies to address these challenges: (1) integrating bioorthogonal cleavage chemistry with genetic code expansion for site-specific SOH incorporation in proteins of interest, enabling controlled activation of redox events, and (2) developing redox-targeted covalent inhibitors (TCIs) to selectively block SOH modifications. By bridging technological innovation with mechanistic inquiry, these strategies not only help elucidate SOH-mediated signaling networks for a better understanding of redox biology, but also hold therapeutic promise for precise redox medicine.

Ap-1-like transcription factors play a crucial role in regulating antioxidant gene expression and protecting cells from oxidative stress. Extensive research on redox regulation in Saccharomyces cerevisiae and Schizosaccharomyces pombe has revealed notable differences in their mechanisms. However, it remains unclear whether filamentous fungi share similarities with either yeast system or employ a distinct signaling strategy. To address this, we investigated the redox signal relay in Aspergillus nidulans, focusing on how peroxiredoxin PrxA and thioredoxin TrxA modulate the activity of the Ap-1-like transcription factor NapA. We demonstrate that PrxA is essential for NapA activation, transmitting the H₂O₂ signal through a disulfide bond between its peroxidatic and resolving cysteines to NapA's Cys558, which subsequently forms an intramolecular disulfide bond with Cys404. Furthermore, we reveal that TrxA, rather than Txl1, is responsible for reducing and inactivating NapA by direct interaction in both the cytoplasm and nucleus, utilizing its own catalytic cysteine residues. These findings establish a mechanistic framework for NapA activation and reduction, providing new insights into oxidative stress responses in filamentous fungi and their divergence from yeast systems.

We report a strategy based on pyridyl-anchored organic small-molecule fluorescent probes to develop a dual-signal sensing platform. The strategy accomplishes an intelligent integration of fluorescence analysis with photoelectrochemical (PEC) sensing, thereby enabling rapid and precise detection of hypochlorite. In this work, the natural dye chromone was selected as the fluorophore for generating fluorescent signals. Meanwhile, by using phenothiazine (PTZ) as the specific recognition group and pyridine as the anchoring moiety, we designed and synthesized a novel organic small-molecule fluorescent probe. The obtained probe was used as a photosensitive material anchored to the TiO2 surface via N → Ti bonds, to form an FTO/TiO2/FPTZ-1 heterostructure-based dual-signal sensing platform for the detection of hypochlorite. This sensing platform has the characteristics of high specificity, sensitivity, and ease of preparation, enabling rapid qualitative fluorescence readout and quantitative photoelectrochemical readout of hypochlorite, with a limit of detection of 0.288 μM for fluorescence and 1.37 nM for PEC.

Chloroplasts are organelles that convert light energy into chemical energy in plants. The potential to integrate chloroplasts into animal cells presents an exciting frontier in synthetic biology, allowing for photo-controllable biochemical processes within these cells. However, the lack of well-established in vitro experimental systems to study chloroplast-animal cell interactions remains a significant challenge. This study investigates the behavior of human cervical cancer HeLa cells and mouse macrophage-like J774.1 cells, along with the light-induced responses of these cells, when introduced into culture media containing spinach-derived chloroplasts. Additionally, we examine isolated cells from Elysia marginata, a sacoglossan sea slug known for its unique ability to acquire and retain functional chloroplasts through a process known as kleptoplasty. Our results show that HeLa cells primarily adhere to chloroplasts with minimal intracellular uptake, while J774.1 cells actively engulf them. Co-incubation with chloroplasts increases the rate of cell death upon light irradiation. In contrast, naturally chloroplast-containing cells from E. marginata exhibit minimal light-induced damage. Excessive reactive oxygen species (ROS) production is observed in HeLa and J774.1 cells co-incubated with chloroplasts under light exposure, suggesting that photoinduced ROS generation contributes to cytotoxicity. These findings highlight three different patterns of interactions between animal cells and chloroplasts and underscore the importance of considering ROS generation induced by light exposure when analyzing chloroplast-animal cell interactions in vitro experimental systems.

For many decades, mitochondria were essentially regarded as the main providers of the adenosine triphosphate (ATP) required to maintain the viability and function of eukaryotic cells, thus the widely popular metaphor "powerhouses of the cell". Besides ATP generation - via intermediary metabolism - these intracellular organelles have also traditionally been known, albeit to a lesser degree, for their notable role in biosynthesis, both as generators of biosynthetic intermediates and/or as the sites of biosynthesis. From the 1990s onwards, the concept of mitochondria as passive organelles providing the rest of the cell, from which they were otherwise isolated, with ATP and biomolecules on an on-demand basis has been challenged by a series of paradigm-shifting discoveries. Namely, it was shown that mitochondria act as signaling effectors to upregulate ATP generation in response to growth-promoting stimuli and are actively engaged, through signaling and epigenetics, in the regulation of a plethora of cellular processes, ultimately deciding cell function and fate. With the focus of mitochondrial research increasingly placed in these "non-classical" functions, the centrality of mitochondrial intermediary metabolism to other mitochondrial functions tends to be overlooked. In this article, we revisit mitochondrial intermediary metabolism and illustrate how its intermediates, by-products and molecular machinery underpin other mitochondrial functions. A certain emphasis is given to frequently overlooked mitochondrial functions, namely the biosynthesis of iron-sulfur (Fe-S) clusters, the only known function shared by all mitochondria and mitochondrion-related organelles. The generation of reactive oxygen species (ROS) and their putative role in signaling is also discussed in detail.

Phytoplankton are responsible for half of the global photosynthesis and form vast blooms in aquatic ecosystems. Bloom demise fuels marine microbial life and is suggested to be mediated by programmed cell death (PCD) induced by diverse environmental stressors. Despite its importance, the molecular basis for algal PCD remains elusive. Here, we reveal novel PCD genes conserved across distant algal lineages using cell-to-cell heterogeneity in the response of the diatom Phaeodactylum tricornutum to oxidative stress. Comparative transcriptomics of sorted sensitive and resilient subpopulations following oxidative stress revealed genes directly linked to their contrasting fates of cell death and survival. Comparing these genes with those found in a large-scale mutant screen in the green alga Chlamydomonas reinhardtii identified functionally relevant conserved PCD gene candidates, including the cysteine protease cathepsin X/Z (CPX). CPX mutants in P. tricornutum CPX1 and C. reinhardtii CYSTEINE ENDOPEPTIDASE 12 (CEP12) exhibited resilience to oxidative stress and infochemicals that induce PCD, supporting a conserved function of these genes in algal PCD. Phylogenetic and predictive structural analyses show that CPX is highly conserved in eukaryotes, and algae exhibit strong structural similarity to human Cathepsin X/Z (CTSZ), a protein linked to various diseases. CPX is expressed by diverse algae across the oceans and correlates with upcoming demise events during toxic Pseudo-nitzschia blooms, providing support for its ecological significance. Elucidating PCD components in algae sheds light on the evolutionary origin of PCD in unicellular organisms and on the cellular strategies employed by the population to cope with stressful conditions.

The recurrent breast cancer (BC) has elicited significant concern due to its rising recurrence rates and associated mortality. However, there is currently no effective detection method to mitigate the deterioration of BC recurrence. The imbalance of HClO content could lead to oxidative stress in the body, which damaging host tissues. Additional, improper regulation of HClO may exacerbate the progression of BC and promote the metastasis of BC cells. Accurately diagnosing and monitoring the HClO levels is crucial for treating BC recurrence. Traditional fluorescent probes for HClO exhibit several limitations, including poor selectivity, susceptibility to photobleaching, a small Stokes shift, and vulnerability to disturbances from excitation and fluorescence self-absorption, which undermine the precise detection of target analytes and restrict their biological applications. Herein, rational designed hypochlorous acid-activatable fluorescent probe (QPIO) was synthesized based on phenothiazine (PZ), quinoline malononitrile (QM), and hemicyanine, which demonstrated high anti-interference capability and a significant Stokes shift for HClO detection. Under various stimuli, QPIO was able to monitor HClO levels in RAW 264.7 and 4T1 cells in the red channel. Furthermore, it elucidated the correlation between HClO concentration and the progression of BC recurrence. Consequently, QPIO was utilized to diagnose recurrent BC, track therapeutic progress, and monitor the recurrence status of breast tumors in mouse models through in vivo HClO fluorescence imaging. It was demonstrated that a close relationship exists between the dynamic changes in HClO levels and BC recurrence, potentially advancing the understanding of the early diagnosis and development of therapeutic agents for recurrent BC.

Chronic alcohol consumption leads to excessive production of reactive oxygen species (ROS), driving oxidative stress that contributes to both alcohol use disorder (AUD) and Alzheimer's disease (AD). This review explores how ROS-mediated mitochondrial dysfunction and neuroinflammation serve as shared pathological mechanisms linking these conditions. We highlight the role of alcohol-induced oxidative damage in exacerbating neurodegeneration and compare ROS-related pathways in AUD and AD. Finally, we discuss emerging therapeutic strategies, including mitochondrial antioxidants and inflammasome inhibitors, that target oxidative stress to mitigate neurodegeneration. Understanding these overlapping mechanisms may provide new insights for preventing and treating ROS-driven neurodegenerative disorders.

The post-translational redox regulation of protein function by cysteine oxidation controls diverse biological processes, from cell division to death. However, most current site-centric paradigms fail to capture the nonlinear and emergent nature of redox regulation in proteins with multiple cysteines. Here, we present a proteoform-centric theory of redox regulation grounded in the i-space. The i-space encapsulates the theoretical landscape of all possible cysteine proteoforms. Using computational approaches, we quantify the vast size of the abstract i-space, revealing its scale-free architecture-elucidating the disproportionate influence of cysteine-rich proteins. We define mathematical rules governing cysteine proteoform dynamics. Their dynamics are inherently nonlinear, context-dependent, and fundamentally constrained by protein copy numbers. Monte Carlo simulations of the human protein PTP1B reveal extensive i-space sampling beyond site-centric models, supporting the "oxiform conjecture". This conjecture posits that highly oxidised proteoforms, molecules bearing multiple oxidised cysteines, are central to redox regulation. In support, even 90%-reduced proteomes can house vast numbers of unique, potentially functioanlly diverse, oxiforms. This framework offers a transformative lens for understanding the redox biology of proteoforms.

Reactive oxygen species (ROS) play a pivotal role in maintaining tissue homeostasis, yet their overabundance can impair normal cellular functions, induce cell death, and potentially lead to neurodegenerative disorders. This study identifies Drosophila Glycoprotein 93 (Gp93) as a crucial factor that safeguards tissue homeostasis and preserves normal neuronal functions by preventing ROS-induced, JNK-dependent apoptotic cell death. Firstly, loss of Gp93 induces JNK-dependent apoptosis primarily through the induction of ROS. Secondary, neuro-specific depletion of Gp93 results in ROS-JNK-mediated neurodegeneration. Thirdly, overexpression of Gp93 effectively curtails oxidative stress and neurodegeneration caused by paraquat exposure or the aging process. Furthermore, these functions of Gp93 can be substituted by its human ortholog, HSP90B1. Lastly, depletion of HSP90B1 in cultured human cells triggers ROS production, JNK activation, and apoptosis. Thus, this study not only unveils a novel physiological function of Gp93, but also provides valuable insights for understanding the physiological and pathological functions of human HSP90B1.

Oxidative stress (OS) is an emerging research area in clinical and biological sciences due to its association with various diseases and physiological processes. OS occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize or repair the damage caused. Chronic oxidative stress is linked to diseases like diabetes, cardiovascular diseases, cancer, and neurodegenerative disorders. Accurate monitoring of OS is crucial for diagnosing diseases, evaluating disease progression, and predicting clinical results. Despite challenges in measuring free radicals due to their short half-life and low concentrations, it can be indirectly assessed through biomarkers like lipid peroxidation, DNA damage, and protein oxidation. The most effective analytical techniques for assessing OS biomarkers in various biological fluids were developed. Furthermore, an in-depth exploration of these various analytical methodologies, underscoring their sensitivity, specificity, and reliability in detecting low concentrations of biomarkers across complex matrices is necessary. A comprehensive literature search was conducted using databases such as Google Scholar, PubMed and Reaxys to identify relevant studies on OS biomarkers. This review explores the evolution of these techniques, highlighting advancements in sample preparation procedures and the specifications of each technique, offering a thorough evaluation of biomarker analysis.

This review addresses oxidative stress and redox signaling in the pancreas under healthy physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione (GSH) in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, with PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the transsulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial reactive oxygen species (ROS), which trigger acinar-to-ductal metaplasia and progression to pancreatic intraepithelial neoplasia (PanIN). ROS are maintained at a sufficient level to promote cell proliferation, while avoiding cell death or senescence through formation of NADPH and GSH and activation of NRF2, HIF-1/2α, and CREB. Redox signaling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, posing significant challenges to healthcare systems. Despite advances in medical interventions, the molecular mechanisms underlying CVDs are not yet fully understood. For decades, protein-coding genes have been the focus of CVD research. However, recent advances in genomics have highlighted the importance of long non-coding RNAs (lncRNAs) in cardiovascular health and disease. Changes in lncRNA expression specific to tissues may result from various internal or external factors, leading to tissue damage, organ dysfunction, and disease. In this review, we provide a comprehensive discussion of the regulatory mechanisms underlying lncRNAs and their roles in the pathogenesis and progression of CVDs, such as coronary heart disease, atherosclerosis, heart failure, arrhythmias, cardiomyopathies, and diabetic cardiomyopathy, to explore their potential as therapeutic targets and diagnostic biomarkers.

The allocation of resources in animals is shaped by adaptive trade-offs aimed at maximizing fitness. At the heart of these trade-offs, lies metabolism and the conversion of food resources into energy, a process mostly occurring in mitochondria. Yet, the conversion of nutrients to utilizable energy molecules (adenosine triphosphate) inevitably leads to the by-production of reactive oxygen species (ROS) that may cause damage to important biomolecules such as proteins or lipids. The 'ROS theory of ageing' has thus proposed that the relationship between lifespan and metabolic rate may be mediated by ROS production. However, the relationship is not as straightforward as it may seem: not only are mitochondrial ROS crucial for various cellular functions, but mitochondria are also actually equipped with antioxidant systems, and many extra-mitochondrial sources also produce ROS. In this review, we discuss how viewing the mitochondrion as a regulator of cellular oxidative homeostasis, not merely a ROS producer, may provide new insights into the role of oxidative stress in the reproduction-survival trade-off. We suggest several avenues to test how mitochondrial oxidative buffering capacity might complement current bioenergetic and evolutionary studies.

Macrophage polarization is a dynamic process driven by a complex interplay of cytokine signaling, metabolism, and epigenetic modifications mediated by pathogens. Upon encountering specific environmental cues, monocytes differentiate into macrophages, adopting either a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype, depending on the cytokines present. M1 macrophages are induced by interferon-gamma (IFN-γ) and are characterized by their reliance on glycolysis and their role in host defense. In contrast, M2 macrophages, stimulated by interleukin-4 (IL-4) and interleukin-13 (IL-13), favor oxidative phosphorylation and participate in tissue repair and anti-inflammatory responses. Metabolism is tightly linked to epigenetic regulation, because key metabolic intermediates such as acetyl-coenzyme A (CoA), α-ketoglutarate (α-KG), S-adenosylmethionine (SAM), and nicotinamide adenine dinucleotide (NAD+) serve as cofactors for chromatin-modifying enzymes, which in turn, directly influences histone acetylation, methylation, RNA/DNA methylation, and protein arginine methylation. These epigenetic modifications control gene expression by regulating chromatin accessibility, thereby modulating macrophage function and polarization. Histone acetylation generally promotes a more open chromatin structure conducive to gene activation, while histone methylation can either activate or repress gene expression depending on the specific residue and its methylation state. Crosstalk between histone modifications, such as acetylation and methylation, further fine-tunes macrophage phenotypes by regulating transcriptional networks in response to metabolic cues. While arginine methylation primarily functions in epigenetics by regulating gene expression through protein modifications, the degradation of methylated proteins releases arginine derivatives like asymmetric dimethylarginine (ADMA), which contribute directly to arginine metabolism-a key factor in macrophage polarization. This review explores the intricate relationships between metabolism and epigenetic regulation during macrophage polarization. A better understanding of this crosstalk will likely generate novel therapeutic insights for manipulating macrophage phenotypes during infections like tuberculosis and inflammatory diseases such as diabetes.

Understanding cellular interaction with nanomaterials represents a subject of great interest for the validation of new diagnostic and therapeutic tools. A full characterization of a designed product includes the evaluation of its impact on specific biological systems, including the study of cell behavior as a response to that particular interaction. Copper and copper-based nanoparticles (CuO NPs) have emerged as valuable building blocks for various biomedical applications such as antibacterial and disinfecting agents for infectious diseases, and the evaluation of the metabolism of food, including the iron required for proteins and enzymes or as drug delivery systems in cancer therapy. In this study, the biological impact of manganese-doped crystalline copper oxide (CuO:Mn) nano-platelets on human normal BJ fibroblasts and human A375 skin melanoma was assessed. The particles were synthesized at room temperature via the hydrothermal method. A complete physicochemical characterization of the materials was performed by employing various techniques including X-ray diffraction, electron microscopy, X-Ray photoelectron spectroscopy, and dynamic light scattering. Morphological investigations revealed a flat structure with nearly straight edges, with sizes spanning in the nanometer range. XRD analysis confirmed the formation of the CuO phase with good crystallinity, while XPS provided insights into the Mn doping. The findings indicate that nano-platelets interact with cells actively by mediating essential molecular processes. The exogenous manganese triggers increased MnSOD production in mitochondria, compensating ROS produced by external stress factors (Cu2+ ions), and mimics the endogenous SODs production, which compensates internal ROS production as it normally results from cell biochemistry. The effect is differentiated in normal cells compared to malignant cells and deserves investigation.

This study investigated the anti-inflammatory and antioxidative effects of ginsenoside Rb3 on experimental periodontitis.

Experimental periodontitis was established by ligating the maxillary first molars. After 21 days of Rb3 treatment, rats were sacrificed for micro-CT and H&E staining analysis and serum assay. qPCR detected the expression of inflammatory genes. IF detected MAPKs pathway activation in periodontal tissues. The effects were determined using LPS-induced RAW264.7 cells. Gene expression levels were determined by qPCR. Intracellular ROS generation was detected by DCFH-DA staining and flow cytometry. WB detected the activation of signaling pathways.

Rb3 inhibited oxidative stress in experimental periodontitis, showing reduced gingivitis and alveolar bone resorption on H&E staining and micro-CT, and reduced iNOS mRNA in rats. Colorimetric results showed that Rb3 increased serum SOD and GSH-Px activities and decreased MDA levels in rats. IF analysis showed that Rb3 inhibited P38, ERK, and JNK activation. Rb3 pretreatment significantly decreased iNOS and IL-6 mRNA expression and ROS in Raw264.7 cells. WB analysis demonstrated that Rb3 blocked the activation of P38 and ERK.

Rb3 inhibits the level of oxidative stress and attenuates gingivitis and alveolar bone resorption in rats via the MAPKs signaling pathway.

Infertility affects 10-15% of reproductive-age couples, with causes ranging from genetic factors to unidentified reasons. Environmental conditions, particularly pollutants, play a significant role in male fertility. Yet, public health policies often overlook reproductive health, despite mounting evidence of pollutants' detrimental repercussion. Understanding this impact is crucial to prevent the effects of dangerous exposure, especially given the high levels of environmental pollutants in today's world. Most of the previous research about the adverse effects from contaminants has been conducted in rodents, with limited human epidemiological research. This article reviews the evidence about the impact of various contaminants (air pollutants, water contaminants, pesticides, herbicides, radiation, heavy metals, and plastics) on male reproductive health, particularly sperm quality and fertility. The literature suggests that exposure to contaminants during fetal development and childhood has irreversible effects, while those of adult exposure are often reversible. These findings highlight the need to alert society about reproductive health threats from certain contaminants. Public authorities should consider this situation when designing health plans, and individuals envisaging fatherhood should be aware of these risks.

Cataracts, the leading cause of blindness globally, are caused by oxidative stress and inflammation, which disrupt lens transparency due to increased accumulation of reactive oxygen species (ROS) as well as protein and DNA damage during aging. Using in vitro, ex vivo, and in vivo models, we determined the protective efficacy of N-acetylcysteine amide (NACA) against oxidative stress-induced and aging-induced cataractogenesis. We found that lens epithelial cells exposed to the oxidative stress inducers hydrogen peroxide (H2O2) or tert-butyl hydroperoxide showed significant ROS accumulation and reduced cellular viability. These effects were inhibited by NACA via the suppression of ROS and thioredoxin-interacting protein (Txnip) expression, a regulator of oxidative stress-related cellular damage and inflammation. In ex vivo lens experiments, NACA significantly reduced H2O2-induced lens opacity and preserved lens integrity. Similarly to NACA-treated lenses ex vivo, the integrity and opacity of aged mouse lenses, when topically instilled with NACA, were preserved and reduced, respectively, and are directly related to reduced Txnip and increased thioredoxin (Trx) expression levels. Overall, our findings demonstrated the protective ability of NACA to abate aberrant redox-active pathways, particularly the ROS/TRX/TXNIP axis, thereby preventing cataractogenesis and preserving eye lens integrity and ultimately impeding aging-related cataracts.

Fluorescent light-up aptamer (FLAP) systems are promising (bio)sensing platforms that are genetically encodable. However, FLAP-mediated detection of each distinct target necessitates either in vitro selection or engineering of nucleic acid sequences. Furthermore, an aptamer that binds an inorganic target or a chemical species with a short lifetime is challenging to realize. Here, we describe a small-molecule approach that makes it possible for a single FLAP system to detect chemically unique, non-fluorogenic, and reactive inorganics. We developed functionalized pre-ligands of RNA aptamers that bind benzylidene imidazolinones (Baby Spinach, Broccolli, Squash). Reactive inorganics, hydrogen sulfide (H2S/HS-) and hydrogen peroxide (H2O2), can specifically convert these pre-ligands into native ligands that fluoresce with FLAPs. Adaptation of this platform to live cells opened an opportunity for constructing whole-cell sensors: Escherichia coli transformed with a Baby Spinach-encoding plasmid and incubated with pre-ligands generated fluorescence in response to exogenous H2S/HS- or H2O2. Leveraging the functional group reactivity of small molecules eliminates the requirement of in vitro selection of a new aptamer sequence or oligonucleotide scaffold engineering for distinct molecular targets. Our method allows for detecting inorganic, short-lived species, thereby advancing FLAP systems beyond their current capabilities.

Benzo[a]pyrene (BaP) is a highly carcinogenic persistent organic pollutant, and biostimulation is an effective strategy to enhance its degradation. This study utilized Bacillus subtilis MSC4 as a BaP-degrading bacterium to investigate the effects of two different fermentation waste liquids as stimulants on BaP degradation. The mechanisms were analyzed and compared at both the cellular and molecular levels. The results showed that the stimulation percentages of yeast Yarrowia lipolytica extracellular metabolites (YEMs) and Lactobacillus plantarum fermentation waste solution (LPS) on the biodegradation of BaP reached 52.8% and 63.4%, respectively, compared to B treatment without biostimulant. Physiological analyses showed that both stimulants repaired cell morphology, more than doubled bacterial biomass, increased EPS secretion, enhanced bacterial activity, and significantly reduced oxidative stress by lowering ROS levels to 75-78% of those in the BaP-stressed group, allowing for repair of oxidative damage. Transcriptomic analysis indicated that both stimulants upregulated pathways related to central carbon metabolism, enhancing cell proliferation and energy supply. Additionally, YEMs promoted electron transport and BaP transmembrane transport and upregulated the synthesis of various monooxygenases, while LPS induced the upregulation of genes encoding quercetin dioxygenase and played a more active role in biofilm formation and enhancing BaP bioavailability. This study reveals the shared and distinct mechanisms by which YEMs and LPS enhance BaP biodegradation, providing theoretical guidance for the application of YEMs and LPS in the bioremediation of BaP-contaminated environments.

Reactive oxygen species (ROS) serve as important signaling molecule, involved in numerous biological processes, particularly in the physiological changes associated with fruit ripening and postharvest handing. This review explores ROS key role in plant fruit ripening and postharvest quality. The mechanism of ROS production and degradation in maintaining ROS homeostasis are analyzed in detail. Fruit ripening is a complex and highly coordinated process involving physiological and biochemical changes. Studies have observed that the content of ROS, mainly hydrogen peroxide (H2O2), dynamically changes in various types of fruits during ripening. Furthermore, ROS have significant effects on fruit softening, color change, and other ripening processes. In addition, in the postharvest stage, the abnormal accumulation of ROS isclosely related to the decline in fruit quality and the occurrence of decay browning, which seriously affects the market value and shelf life of fruit. Overall, this review demonstrates the crucial role of ROS in regulating the ripening process and postharvest quality of fruit.

Small heat shock proteins (sHSPs) are common molecular chaperone proteins that function in various biological processes, and serve indispensable roles in maintaining cellular protein homeostasis and regulating the hydrolysis of unfolded proteins. HSP22 is a member of the sHSP family that is primarily expressed in the heart and skeletal muscle, as well as in various types of cancer. There have been important findings concerning the role of HSP22 in cardiovascular diseases. The aim of the present study was to provide insights into the various molecular mechanisms by which HSP22 functions in the heart, including oxidative stress, autophagy, apoptosis, the subcellular distribution of proteins and the promoting effect of proteasomes. In addition, drugs and cytokines, including geranylgeranylacetone, can exert protective effects on the heart by regulating the expression of HSP22. Based on increasingly abundant research, HSP22 may be considered a potential therapeutic target in cardiovascular diseases.

Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis.

Tanshinone IIA (Tan IIA) inhibits BC progression, however, the underlying mechanism remains largely undefined.

The cytotoxicity of Tan IIA was assessed by CCK-8 and LDH assays. Ferroptosis was monitored by the level of MDA, Fe2+, lipid ROS and GSH. IHC and western blot were employed to detect the localization and expression of SLC7A11, PIAS4, KDM1A and other key molecules. The SUMOylation of SLC7A11 was detected by Ni-beads pull-down assay and Co-IP. Luciferase and ChIP assays were employed to detect the direct association between KDM1A and PIAS4 promoter. The proliferative and metastatic properties of BC cells were assessed by colony formation, CCK-8 and Transwell assays, respectively. The in vitro findings were verified in xenograft and lung metastasis models.

Tan IIA promoted ferroptosis by suppressing SLC7A11 in BC cells. Silencing of PIAS4 or KDM1A inhibited cell growth and metastasis in BC. Mechanistically, PIAS4 facilitated the SUMOylation of SLC7A11 via direct binding to SLC7A11, and KDM1A acted as a transcriptional activator of PIAS4. Functional studies further revealed that Tan IIA decreased KDM1A expression, thus suppressing PIAS4 expression transcriptionally. The inhibition of PIAS4-dependent SUMOylation of SLC7A11 further induced ferroptosis, thereby inhibiting proliferation and metastasis in BC.

Tan IIA promoted ferroptosis and inhibited tumor growth and metastasis via suppressing KDM1A/PIAS4/SLC7A11 axis.

Mounting evidence over the past decades has demonstrated the therapeutic potential of targeting endoplasmic reticulum (ER) stress signaling in cancer. Naphthalimdes exert their anti-cancer activities in a variety of ways. However, the effects of naphthalimides on ER stress are rarely reported. In this study, based on RNA-sequencing analysis, we observed that 9C, a naphthalimide derivative, could trigger ER stress to activate death receptor signaling and autophagy. Pretreatment of ER stress inhibitor, such as salubrinal, and autophagy inhibitor, such as 3-methyladenine (3-MA), partially reversed 9C-induced inhibition of cell growth. Furthermore, our results unveiled a reactive oxygen species (ROS)-dependent inhibitory effect of 9C. In addition, 9C inhibited colorectal cancer (CRC) cells migration and invasion. Removal of ROS using N-acetyl-L-cysteine (NAC) attenuated the expression of ATF4, CHOP, death receptors, E-cadherin, and the apoptosis and autophagy related proteins. Taken together, our results suggested that ROS-mediated ER stress, migration, and invasion is responsible for the therapeutic potential of naphthalimides including 9C in CRC.

Fluctuations of intracellular H2O2 level are intricately linked to diverse biological processes, e.g., cellular proliferation, biosynthesis, and metabolic activities. The dynamics of intracellular H2O2 levels holds immense significance as it represents a pivotal metabolite within the realm of free radicals. This study describes a novel internal standard assisted surface enhanced Raman scattering (SERS) nanoprobe based on H2O2 boronic acid oxide group for precise detection of H2O2 levels in vitro and within living cells. The nanoprobe consists of a core molecule shell Au nanostar (Au@MPBN@Au NPs) embedded with internal marker (4-mercaptobenzonitrile, 4-MPBN) as a high plasma active SERS substrate and a 4-mercaptophenylboronic acid (4-MPBA) molecule fixed on its surface as H2O2 recognition unit. The presence of H2O2 leads to a decrease of the band intensity for B-O group at 998 cm-1, while the absorption for the internal standard molecule 4-MPBN at 2223 cm-1 remains unaffected by the variation of external environment. H2O2 quantification may be achieved by analyzing the ratio of band intensities at I2223 cm-1/I998 cm-1, with a linear relationship between I2223cm-1/I998cm-1 and H2O2 concentration within the range of 5-100 μM, along with a limit of detection (LOD) of 1.97 μM. Meanwhile, due to the presence of internal marker molecules, measurement errors caused by environmental or instrumental fluctuations can be calibrated in real-time. The AuNPs/4-MPBN/4-MPBA nanoprobe provides an accurate tool for dynamic monitoring and quantitative characterization of intracellular H2O2 content during cell apoptosis or other cell growth processes.

Cold stress has a huge impact on the growth and development of cotton, presenting a significant challenge to its productivity. Comprehending the complex molecular mechanisms that control the reaction to CS is necessary for developing tactics to improve cold tolerance in cotton. This review paper explores how cotton responds to cold stress by regulating gene expression, focusing on both activating and repressing specific genes. We investigate the essential roles that transcription factors and regulatory elements have in responding to cold stress and controlling gene expression to counteract the negative impacts of low temperatures. Through a comprehensive examination of new publications, we clarify the intricacies of transcriptional reprogramming induced by cold stress, emphasizing the connections between different regulatory elements and signaling pathways. Additionally, we investigate the consecutive effects of cold stress on cotton yield, highlighting the physiological and developmental disturbances resulting from extended periods of low temperatures. The knowledge obtained from this assessment allows for a more profound comprehension of the molecular mechanisms that regulate cold stress responses, suggesting potential paths for future research to enhance cold tolerance in cotton by utilizing targeted genetic modifications and biotechnological interventions.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes necessitating early intervention to impede progression, despite current clinical treatments focusing on advanced stages. Essential oils from Fructus Alpiniae zerumbet (EOFAZ) have demonstrated efficacy in protecting against high glucose (HG)-induced Müller cell activation and DR development. This study introduced a reactive oxidative species (ROS)-responsive drug delivery system (NPSPHE@EOFAZ) targeting early DR stages and oxidative stress. Our engineered nanoparticles effectively deliver EOFAZ into HG-exposed Müller cells by detecting and responding to elevated oxidative stress levels. The NPSPHE@EOFAZ significantly inhibited abnormal cell growth, reduced oxidative stress, and alleviated inflammation in vitro. In vivo experiments on diabetic mice with DR revealed that NPSPHE@EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation while also alleviating organ damage in the heart, liver, spleen, lung, and kidney. These findings underscore the potential of NPSPHE@EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.

Oral diseases rank among the most prevalent clinical conditions globally, typically involving detrimental factors such as infection, inflammation, and injury in their occurrence, development, and outcomes. The concentration of reactive oxygen species (ROS) within cells has been demonstrated as a pivotal player in modulating these intricate pathological processes, exerting significant roles in restoring oral functionality and maintaining tissue structural integrity. Due to their enzyme-like catalytic properties, unique composition, and intelligent design, ROS-based nanomaterials have garnered considerable attention in oral nanomedicine. Such nanomaterials have the capacity to influence the spatiotemporal dynamics of ROS within biological systems, guiding the evolution of intra-ROS to facilitate therapeutic interventions. This paper reviews the latest advancements in the design, functional customization, and oral medical applications of ROS-based nanomaterials. Through the analysis of the components and designs of various novel nanozymes and ROS-based nanoplatforms responsive to different stimuli dimensions, it elaborates on their impacts on the dynamic behavior of intra-ROS and their potential regulatory mechanisms within the body. Furthermore, it discusses the prospects and strategies of nanotherapies based on ROS scavenging and generation in oral diseases, offering alternative insights for the design and development of nanomaterials for treating ROS-related conditions.