Ciprofloxacin is a novel anti-ferroptotic antibiotic.

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.

Advances in relieving exercise fatigue for curcumin: Molecular targets, bioavailability, and potential mechanism.

Intense and prolonged physical activity can lead to a decrease in muscle capacity, making it difficult to maintain the desired exercise intensity and resulting in exercise fatigue. The long-term effects of exercise fatigue can be very damaging to the body, so it is an urgent problem to be addressed. The intervention of foodborne active substances will be an effective measure. There is growing evidence that the molecular structure and function of curcumin have a positive effect on relieving fatigue. In this review, we summarize curcumin's molecular structure, which enables it to bind to a wealth of molecular targets, regulate signaling pathways, and thus alleviate exercise fatigue through a variety of mechanisms, including reducing oxidative stress, inhibiting inflammation, reducing metabolite accumulation, and regulating energy metabolism. The effects of curcumin on fatigue-related markers were analyzed from the perspective of animal models and human models and based on the bidirectional interaction between curcumin and intestinal microbiota: Intestinal microbiota can transform curcumin, and curcumin regulates gut microbiota through metabolic pathways, providing a new perspective for alleviating fatigue. This review contributes to a more comprehensive understanding of the possible molecular mechanisms of curcumin in anti-fatigue and provides a new possibility for the development of functional foods in the future.

Controlling nanoparticle placement in Au/TiO2 inverse opal photocatalysts.

Gold nanoparticle-loaded titania (Au/TiO2) inverse opals are highly ordered three-dimensional photonic structures with enhanced photocatalytic properties. However, fine control over the placement of the Au nanoparticles in the inverse opal structures remains challenging with traditional preparative methods. Here, we present a multi-component co-assembly strategy to prepare high-quality Au/TiO2 inverse opal films in which Au nanoparticles are either located on, or inside the TiO2 matrix, as verified using electron tomography. We report that Au nanoparticles embedded in the TiO2 support exhibit enhanced thermal and mechanical stability compared to non-embedded nanoparticles that are more prone to both leaching and sintering.

Macropinocytosis inhibits alkaliptosis in pancreatic cancer cells through fatty acid uptake.

Alkaliptosis, a form of regulated cell death, is characterized by lysosomal dysfunction and intracellular pH alkalinization. The pharmacological induction of alkaliptosis using the small molecule compound JTC801 has emerged as a promising anticancer strategy in various types of cancers, particularly pancreatic ductal adenocarcinoma (PDAC). In this study, we investigate a novel mechanism by which macropinocytosis, an endocytic process involving the uptake of extracellular material, promotes resistance to alkaliptosis in human PDAC cells. Through lipid metabolomics analysis and functional studies, we demonstrate that the inhibition of alkaliptosis by fatty acids, such as oleic acid, is not dependent on endogenous synthetic pathways but rather on exogenous uptake facilitated by macropinocytosis. Consequently, targeting macropinocytosis through pharmacological approaches (e.g., using EIPA or EHoP-016) or genetic interventions (e.g., RAC1 knockdown) effectively enhances JTC801-induced alkaliptosis in human PDAC cells. These findings provide compelling evidence that the modulation of macropinocytosis can increase the sensitivity of cancer cells to alkaliptosis inducers.

Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus.

LGALS9, also known as Galectin-9 and a member of the ß-galactosidase family, plays a crucial role in immune regulation. However, its expression and function in CD8 T cells, as well as its association with cytotoxic T lymphocytes (CTL), remain unclear. This study aims to investigate LGALS9 expression patterns in human circulating CD8 T lymphocytes and elucidate its clinical significance in Systemic Lupus Erythematosus (SLE). Blood samples from 56 healthy controls and 50 new-onset SLE patients were collected. Flow cytometry was utilized to analyze LGALS9 expression in circulating CD8 T lymphocytes via intracellular staining. Compared to LGALS9 + CD8 + T cells, LGALS9-CD8 + T cells showed increased secretion of Granzyme B (GZMB) and Perforin, along with elevated expression levels of GPR56, CX3CR1, KLRD1, KLRF1, PD1, and CD29. A higher proportion of Tn (naive T cells) and TCM (central memory T cells) showed LGALS9 positivity, compared to TEM (effector memory T cells) and TEMRA (terminally differentiated effector memory T cells re-expressing CD45RA). Clinically, the downregulation of LGALS9 expression was significant in SLE patients. LGALS9 + CD8 + T cells exhibited an Area Under the Curve (AUC) of 0.6916, while CX3CR1 + in LGALS9 + CD8 + T cells had an AUC of 0.6478, and KLRF1 + had an AUC of 0.6419, for distinguishing SLE from healthy individuals. In conclusion, CD8 + LGALS9 + T cells display characteristics of low cytotoxicity, and their reduction is evident in SLE patients, potentially implicating them in SLE pathogenesis and providing diagnostic assistance.

Deconvoluting the Individual Effects of Nanoparticle Proximity and Size in Thermocatalysis.

Nanoparticle (NP) size and proximity are two physical descriptors applicable to practically all NP-supported catalysts. However, with conventional catalyst design, independent variation of these descriptors to investigate their individual effects on thermocatalysis remains challenging. Using a raspberry-colloid-templating approach, we synthesized a well-defined catalyst series comprising Pd12Au88 alloy NPs of three distinct sizes and at two different interparticle distances. We show that NP size and interparticle distance independently control activity and selectivity, respectively, in the hydrogenation of benzaldehyde to benzyl alcohol and toluene. Surface-sensitive spectroscopic analysis indicates that the surfaces of smaller NPs expose a greater fraction of reactive Pd dimers, compared to inactive Pd single atoms, thereby increasing intrinsic catalytic activity. Computational simulations reveal how a larger interparticle distance improves catalytic selectivity by diminishing the local benzyl alcohol concentration profile between NPs, thus suppressing its readsorption and consequently, undesired formation of toluene. Accordingly, benzyl alcohol yield is maximized using catalysts with smaller NPs separated by larger interparticle distances, overcoming activity-selectivity trade-offs. This work exemplifies the high suitability of the modular raspberry-colloid-templating method as a model catalyst platform to isolate individual descriptors and establish clear structure-property relationships, thereby bridging the materials gap between surface science and technical catalysts.

Ferroptosis: principles and significance in health and disease.

Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across a wide range of diseases. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Additionally, we examine the involvement of ferroptosis in various pathological conditions, including cancer, neurodegenerative diseases, sepsis, ischemia-reperfusion injury, autoimmune disorders, and metabolic disorders. Specifically, we explore the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Furthermore, we discuss pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Lastly, we elucidate the interplay between ferroptosis and other forms of regulated cell death. Such insights hold promise for advancing our understanding of ferroptosis in the context of human health and disease.

An integrated method for the leakage fault mode diagnosis and life prediction of the reactor coolant pump.

The reactor coolant pump is a key equipment in a nuclear power plant. If the leakage exceeds a certain threshold, it may cause reactor overheating and shutdown. The reactor coolant pump leakage fault usually has two problems: corrosion and scaling. Accurately and efficiently diagnosing the leakage fault mode as early as possible and predicting its remaining useful life (RUL) are important for taking timely maintenance measures. In this paper, an integrated method is proposed. First, the cross-sectional area of the first seal is extracted as a fault indicator. The motivation is that corrosion may enlarge the cross-sectional area, and scaling may reduce the cross-sectional area. Based on the fluid mechanics theory, an integrated model with several uncertain parameters is established among the cross-sectional area, temperature, and leakage at the inlet and outlet of the first seal. In the diagnosing process, a modified change-detection method is proposed to detect the starting point of degradation. Then, the unknown parameters in the previous relation are estimated, and the degrading data before the starting point of degradation are used to diagnose the leakage fault mode. Second, a time-series model of the autoregressive integrated moving average (ARIMA) is established to predict the remaining useful life based on the degrading data after the starting point of degradation. Finally, the leakage degrading data from six reactor coolant pumps of a nuclear power plant is used to perform the leakage fault mode diagnosis and life prediction with degradation point detection error rates not exceeding 4%, fault mode diagnosis correction rates 100% and practical RUL predicting results, which proves that the proposed integrated method is accurate and efficient. The proposed integrated method combines the advantages of both the physical model diagnosis and the data-driven model diagnosis and innovatively make use of the quantity of flow from the output side of the primary pump as the monitoring indicator and the cross-sectional area as the characteristic index together to diagnose the leakage fault mode happened to the seal and predict its RUL, which can meet the needs of actual operation and maintenance to ensure a healthy and stable operation of the pump and prevent unexpected shutdowns of nuclear power plants and serious accidents.

Targeting GPX4 in ferroptosis and cancer: chemical strategies and challenges.

Selenoprotein glutathione peroxidase 4 (GPX4) serves as a crucial suppressor of oxidative stress-induced ferroptosis, making it an attractive target for disease therapy. Here, we discuss recent strategies and challenges associated with targeting GPX4 through covalent inhibitors, proteolysis targeting chimera (PROTAC) degraders, and cell-type-specific degraders in the context of cancer.

Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.

Sepsis, a life-threatening condition resulting from a dysregulated response to pathogen infection, poses a significant challenge in clinical management. Here, we report a novel role for the autophagy receptor NCOA4 in the pathogenesis of sepsis. Activated macrophages and monocytes secrete NCOA4, which acts as a mediator of septic death in mice. Mechanistically, lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, induces NCOA4 secretion through autophagy-dependent lysosomal exocytosis mediated by ATG5 and MCOLN1. Moreover, bacterial infection with E. coli or S. enterica leads to passive release of NCOA4 during GSDMD-mediated pyroptosis. Upon release, extracellular NCOA4 triggers the activation of the proinflammatory transcription factor NFKB/NF-κB by promoting the degradation of NFKBIA/IκB molecules. This process is dependent on the pattern recognition receptor AGER, rather than TLR4. In vivo studies employing endotoxemia and polymicrobial sepsis mouse models reveal that a monoclonal neutralizing antibody targeting NCOA4 or AGER delays animal death, protects against organ damage, and attenuates systemic inflammation. Furthermore, elevated plasma NCOA4 levels in septic patients, particularly in non-survivors, correlate positively with the sequential organ failure assessment score and concentrations of lactate and proinflammatory mediators, such as TNF, IL1B, IL6, and HMGB1. These findings demonstrate a previously unrecognized role of extracellular NCOA4 in inflammation, suggesting it as a potential therapeutic target for severe infectious diseases. Abbreviation: BMDMs: bone marrow-derived macrophages; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; ELISA: enzyme-linked immunosorbent assay; LPS: lipopolysaccharide; NO: nitric oxide; SOFA: sequential organ failure assessment.

Gold nanocluster-based ratiometric fluorescence immunoassay for broad-spectrum screening of five eugenols.

BACKGROUND: Eugenol compounds (EUGs), which share chemical similarities with eugenol, belong to a group of phenolic compounds primarily found in clove oil. They are highly valued by fish dealers due to their exceptional anesthetic properties, playing a crucial role in reducing disease incidence and mortality during the transportation of live fish. Despite their widespread use, the safety of EUGs remains a contentious topic, raising concerns about the safety of aquatic products. This underscores the need for efficient and sensitive analytical methods for detecting EUGs. RESULTS: Nanomaterial-based ratiometric fluorescence immunoassay has gained increasing attention due to its integration of the immunoassay's excellent specificity and compatibility for high-throughput analysis, coupled with the exceptional sensitivity and anti-interference capabilities of ratiometric fluorescence assays. In this study, we developed a sensitive ratiometric fluorescence immunoassay for screening five EUGs. This method employs a broad-specificity monoclonal antibody (mAb) as a recognition reagent, selective for five EUGs. It leverages the horseradish peroxidase (HRP)-triggered formation of fluorescent 2,3-diaminophenazine (DAP) and the quenching of fluorescent gold clusters (Au NCs) for detection. The assay's detection limits for eugenol, isoeugenol, eugenol methyl eugenol, methyl isoeugenol, and acetyl isoeugenol in tilapia fish and shrimp were found to be 9.8/19.5 µg/kg, 0.11/0.22 µg/kg, 19/36 Tilapia ng/kg, 8/16 ng/kg, and 3.0/6.1 µg/kg, respectively. Furthermore, when testing spiked Tilapia fish and shrimp samples, recoveries ranging from 84.1 to 111.9 %, with the coefficients of variation staying below 7.1 % was achieved. SIGNIFICANCE: This work introduces an easy-to-use, broad-specificity, and highly sensitive method for the screening of five EUGs at a pg/mL level, which not only provides a high-throughput strategy for screening eugenol-type fish anesthetics in aquatic products, but also can serve as a benchmark for developing immunoassays for other small molecular pollutants, rendering potent technological support for guarding food safety and human health.

Ferroptotic therapy in cancer: benefits, side effects, and risks.

Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various cancer types. However, it can lead to side effects, including immune cell death, bone marrow impairment, liver and kidney damage, cachexia (severe weight loss and muscle wasting), and secondary tumorigenesis. In this review, we discuss the advantages and offer an overview of the diverse range of documented side effects. Furthermore, we examine the underlying mechanisms and explore potential strategies for side effect mitigation.

Alkaliptosis induction counteracts paclitaxel-resistant ovarian cancer cells via ATP6V0D1-mediated ABCB1 inhibition.

Paclitaxel serves as the cornerstone chemotherapy for ovarian cancer, yet its prolonged administration frequently culminates in drug resistance, presenting a substantial challenge. Here we reported that inducing alkaliptosis, rather than apoptosis or ferroptosis, effectively overcomes paclitaxel resistance. Mechanistically, ATPase H+ transporting V0 subunit D1 (ATP6V0D1), a key regulator of alkaliptosis, plays a pivotal role by mediating the downregulation of ATP-binding cassette subfamily B member 1 (ABCB1), a multidrug resistance protein. Both ATP6V0D1 overexpression through gene transfection and pharmacological enhancement of ATP6V0D1 protein stability using JTC801 effectively inhibit ABCB1 upregulation, resulting in growth inhibition in drug-resistant cells. Additionally, increasing intracellular pH to alkaline (pH 8.5) via sodium hydroxide application suppresses ABCB1 expression, whereas reducing the pH to acidic conditions (pH 6.5) with hydrochloric acid amplifies ABCB1 expression in drug-resistant cells. Collectively, these results indicate a potentially effective therapeutic strategy for targeting paclitaxel-resistant ovarian cancer by inducing ATP6V0D1-dependent alkaliptosis.

A preliminary study of roxadustat in the treatment of aplastic anemia patients with inadequate erythroid responses.

Some aplastic anemia(AA) patients only have partial hematological responses after immunosuppressive therapy. Failure to achieve complete normalization of blood counts, particularly hemoglobin, will reduce their quality of life. This open-label pilot study was conducted to evaluate the efficacy and safety of roxadustat in this setting. A total of 14 patients with AA who had inadequate erythroid response after immunosuppressive therapy were included in the study. The primary efficacy endpoint was hemoglobin response at week 8 after roxadustat treatment. The median duration of roxadustat therapy was 14 (4-30) weeks, with 12 patients receiving roxadustat for ≥ 8 weeks. At week 8, nine patients (9/14, 64.3%) had their hemoglobin rising for at least 15 g/L, with two patients (2/14, 14.3%) achieving normal hemoglobin levels. By the last follow-up, hemoglobin responses were observed in 10 patients (10/14, 71.4%), with 4 patients(4/14, 28.6%) having normal hemoglobin levels. Roxadustat was tapered or discontinued in four responded patients; one relapsed after 12 weeks of tapering, and three maintained their response. Four patients (4/14, 28.6%) experienced mild adverse effects during therapy. Roxadustat is safe and well tolerated by patients with AA. Treatment with the hypoxia-inducible factor prolyl hydroxylase inhibitor improves hemoglobin levels in AA patients with inadequate erythroid responses.

Toward Real Scenery: A Lightweight Tomato Growth Inspection Algorithm for Leaf Disease Detection and Fruit Counting.

The deployment of intelligent surveillance systems to monitor tomato plant growth poses substantial challenges due to the dynamic nature of disease patterns and the complexity of environmental conditions such as background and lighting. In this study, an integrated cascade framework that synergizes detectors and trackers was introduced for the simultaneous identification of tomato leaf diseases and fruit counting. We applied an autonomous robot with smartphone camera to collect images for leaf disease and fruits in greenhouses. Further, we improved the deep learning network YOLO-TGI by incorporating Ghost and CBAM modules, which was trained and tested in conjunction with premier lightweight detection models like YOLOX and NanoDet in evaluating leaf health conditions. For the cascading with various base detectors, we integrated state-of-the-art trackers such as Byte-Track, Motpy, and FairMot to enable fruit counting in video streams. Experimental results indicated that the combination of YOLO-TGI and Byte-Track achieved the most robust performance. Particularly, YOLO-TGI-N emerged as the model with the least computational demands, registering the lowest FLOPs at 2.05 G and checkpoint weights at 3.7 M, while still maintaining a mAP of 0.72 for leaf disease detection. Regarding the fruit counting, the combination of YOLO-TGI-S and Byte-Track achieved the best R2 of 0.93 and the lowest RMSE of 9.17, boasting an inference speed that doubles that of the YOLOX series, and is 2.5 times faster than the NanoDet series. The developed network framework is a potential solution for researchers facilitating the deployment of similar surveillance models for a broad spectrum of fruit and vegetable crops.

Investigating the impact of ultrasound-assisted cellulase pretreatment on the nutrients, phytic acid, and phenolics bioaccessibility in sprouted brown rice.

This study aimed to elucidate the impact of ultrasound-assisted cellulase (UC) pretreatment on nutrients, phytic acid, and the bioavailability of phenolics during brown rice sprouting. It sought to unveil the underlying mechanisms by quantifying the activity of key enzymes implicated in these processes. The sprouted brown rice (SBR) surface structure was harmed by the UC pretreatment, which also increased the amount of γ-oryzanol and antioxidant activity in the SBR. Concurrently, the UC pretreatment boosted the activity of phytase, glutamate decarboxylase, succinate semialdehyde dehydrogenase, Gamma-aminobutyric acid (GABA) transaminase, chalcone isomerase, and phenylalanine ammonia lyase, thereby decreasing the phytic acid content and increasing the GABA, flavonoid, and phenolic content in SBR. In addition, UC-pretreated SBR showed increased phenolic release and bioaccessibility during in vitro digestion when compared to the treated group. These findings might offer theoretical direction for using SBR to maximize value.

Lipopolysaccharide delivery systems in innate immunity.

Lipopolysaccharide (LPS), a key component of the outer membrane in Gram-negative bacteria (GNB), is widely recognized for its crucial role in mammalian innate immunity and its link to mortality in intensive care units. While its recognition via the Toll-like receptor (TLR)-4 receptor on cell membranes is well established, the activation of the cytosolic receptor caspase-11 by LPS is now known to lead to inflammasome activation and subsequent induction of pyroptosis. Nevertheless, a fundamental question persists regarding the mechanism by which LPS enters host cells. Recent investigations have identified at least four primary pathways that can facilitate this process: bacterial outer membrane vesicles (OMVs); the spike (S) protein of SARS-CoV-2; host-secreted proteins; and host extracellular vesicles (EVs). These delivery systems provide new avenues for therapeutic interventions against sepsis and infectious diseases.

Development of broad-spectrum immunoassay with monoclonal antibody to detect five eugenols and study of their molecular recognition mechanism.

In this study, three eugenol fragment-containing haptens were synthesized, and a monoclonal antibody (mAb) selective for five commonly-found eugenol compounds (EUGs, i.e., eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, and acetyl isoeugenol) was obtained. Based on this mAb, a broad-spectrum indirect competitive ELISA for high-throughput detection of five EUGs was developed. The detection limits for eugenol, isoeugenol, methyl eugenol, methyl isoeugenol and acetyl isoeugenol in both tilapia and shrimp samples were 25.3/ 50.6 µg/kg, 0.075/0.15 µg/kg, 0.48/0.96 µg/kg, 0.16/0.32 µg/kg, and 18.16/36.32 µg/kg, respectively. The recoveries for five EUGs ranged from 80.4 to 114.0 % with a coefficient of variation less than 11.5 %. Moreover, homology modelling and molecular docking were conducted to elucidate the interactions mechanism of mAb-EUGs. The work provides a promising tool for high-throughput screening of EUGs in aquatic products, which can serve as a benchmark for designing haptens and developing immunoassays for other small molecules.

Diverse functions of cytochrome c in cell death and disease.

The redox-active protein cytochrome c is a highly positively charged hemoglobin that regulates cell fate decisions of life and death. Under normal physiological conditions, cytochrome c is localized in the mitochondrial intermembrane space, and its distribution can extend to the cytosol, nucleus, and extracellular space under specific pathological or stress-induced conditions. In the mitochondria, cytochrome c acts as an electron carrier in the electron transport chain, facilitating adenosine triphosphate synthesis, regulating cardiolipin peroxidation, and influencing reactive oxygen species dynamics. Upon cellular stress, it can be released into the cytosol, where it interacts with apoptotic peptidase activator 1 (APAF1) to form the apoptosome, initiating caspase-dependent apoptotic cell death. Additionally, following exposure to pro-apoptotic compounds, cytochrome c contributes to the survival of drug-tolerant persister cells. When translocated to the nucleus, it can induce chromatin condensation and disrupt nucleosome assembly. Upon its release into the extracellular space, cytochrome c may act as an immune mediator during cell death processes, highlighting its multifaceted role in cellular biology. In this review, we explore the diverse structural and functional aspects of cytochrome c in physiological and pathological responses. We summarize how posttranslational modifications of cytochrome c (e.g., phosphorylation, acetylation, tyrosine nitration, and oxidation), binding proteins (e.g., HIGD1A, CHCHD2, ITPR1, and nucleophosmin), and mutations (e.g., G41S, Y48H, and A51V) affect its function. Furthermore, we provide an overview of the latest advanced technologies utilized for detecting cytochrome c, along with potential therapeutic approaches related to this protein. These strategies hold tremendous promise in personalized health care, presenting opportunities for targeted interventions in a wide range of conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer.

Targeting cuproplasia and cuproptosis in cancer.

Copper, an essential trace element that exists in oxidized and reduced forms, has pivotal roles in a variety of biological processes, including redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy and immune modulation; maintaining copper homeostasis is crucial as both its deficiency and its excess are deleterious. Dysregulated copper metabolism has a dual role in tumorigenesis and cancer therapy. Specifically, cuproplasia describes copper-dependent cell growth and proliferation, including hyperplasia, metaplasia and neoplasia, whereas cuproptosis refers to a mitochondrial pathway of cell death triggered by excessive copper exposure and subsequent proteotoxic stress (although complex interactions between cuproptosis and other cell death mechanisms, such as ferroptosis, are likely and remain enigmatic). In this Review, we summarize advances in our understanding of copper metabolism, the molecular machineries underlying cuproplasia and cuproptosis, and their potential targeting for cancer therapy. These new findings advance the rapidly expanding field of translational cancer research focused on metal compounds.