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Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbiosis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione (GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating inflammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

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PURPOSE OF REVIEW: B-cell depletion therapy, including anti-CD20 and anti-CD19 therapies, is increasingly used for a variety of autoimmune and conditions, including those affecting the central nervous system. However, B-cell depletion therapy use can be complicated by adverse effects associated with administration and immunosuppression. This review aims to summarize the application of anti-CD20 and anti-CD19 therapies for the pediatric neurologist and neuroimmunologist. RECENT FINDINGS: Most existing literature come from clinical trials with adult patients, although more recent studies are now capturing the effects of these therapies in children. The most common side effects include infusion related reactions and increased infection risk from immunosuppression. Several strategies can mitigate infusion related reactions. Increased infections due to persistent hypogammaglobulinemia can benefit from replacement immunoglobulin. B-cell depletion therapies can be safe and effective in pediatric patients. Anticipation and mitigation of common adverse effects through primary prevention strategies, close monitoring, and appropriate symptomatic management can improve safety and tolerability.

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Polymer microgels are swollen macromolecular networks with a typical size of hundred of nanometers to several microns that show an extraordinary open and responsive architecture to different external stimuli, being therefore important candidates for nanobiotechnology and nanomedical applications such as biocatalysis, sensing and drug delivery. It is therefore crucial to understand the delicate balance of physical-chemical interactions between the polymer backbone and solvent molecules that to a high extent determine their responsivity. In particular, the co-nonsolvency effect of poly(N-isopropylacrylamide) in aqueous alcohols is highly discussed, and there is a disagreement between molecular dynamics (MD) simulations (from literature) of the preferential adsorption of alcohol on the polymer chains and the values obtained by several empirical methods that mostly probe the bulk solvent properties. It is our contention that the most efficacious method for addressing this problem requires a nanoscopic method that can be combined with spectroscopy and record fluorescence spectra and super-resolved fluorescence lifetime images of microgels labeled covalently with the solvatochromic dye Nile Red. By employing this approach, we could simultaneously resolve the structure of sub-micron size objects in the swollen and in the collapsed state and estimate the solvent composition inside of them in - mixtures for two very different polymer architectures. We found an outstanding agreement between the MD simulations and our results that estimate a co-solvent molar fraction excess of approximately 3 with a very flat profile in the lateral direction of the microgel.

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Intratumoral regulatory T cells (Tregs) express high levels of CD25 and TIGIT, which are also recognized as markers of effector T cell (Teff) activation. Targeting these molecules each alone with monoclonal antibodies (mAbs) poses a risk of concurrently depleting both Teffs and peripheral Tregs, thereby compromising the effectiveness and selectivity of intratumoral Treg depletion. Here, leveraging the increased abundance of CD25+ TIGIT+ double positive Tregs in the solid tumor microenvironment (but not in peripheral tissues), we explored the feasibility of using a CD25×TIGIT bispecific antibody (bsAb) to selectively deplete intratumoral Tregs. We initially constructed a bsAb co-targeting mouse CD25 and TIGIT, NSWm7210, and found that NSWm7210 conferred enhanced intratumoral Treg depletion, Teff activation, and tumor suppression as compared to the parental monotherapies in mouse models. We subsequently constructed a bsAb co-targeting human CD25 and TIGIT (NSWh7216), which preferentially eliminated CD25+ TIGIT+ double positive cells over single positive cells in vitro. NSWh7216 exhibited enhanced anti-tumor activity without toxicity of peripheral Tregs in CD25 humanized mice compared to the parental monotherapies. Our study illustrates the use of CD25×TIGIT bsAbs as effective agents against solid tumors based on selective depletion of intratumoral Tregs.

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The lack of soil moisture-based irrigation intervals, poor distribution of irrigation water among users, and the time-based and spatial variability of water supply have been challenges for the productivity of irrigation schemes in the Lower Kulfo catchment, Southern Ethiopia. This study was conducted to develop soil moisture-based irrigation intervals and to evaluate irrigation water delivery and field level irrigation efficiencies. Soil water content, and flow along the canal and in the field were measured directly, and irrigation duty was estimated by using CropWat 8 model. To minimize water stress or excess problems, irrigation needs to be applied when soil water content drops to 35.7 % for onion and pepper, 34.4 %% for watermelon, and 32.5 % for wheat and maize from field capacity. However, irrigation was applied at 36.2 % for onion, 35.4 % for watermelon, 36.4 % for pepper, 36.2 % for maize, and 35 % for wheat in the existing irrigation scheme that increased irrigation amount in the field. The average percentage of soil moisture depletion (p) at time of irrigation was 27.4 %, which was below the recommended value. The average adopted irrigation and design irrigation interval were 4 & 6 days for onion and pepper, 5 & 7 days for watermelon and wheat, and 6 & 7 days for maize, respectively. The mean irrigation adequacy and dependability of the irrigation scheme in the lower Kulfo catchment were 1 & 0 for Arba Minch irrigation scheme, 0.5 & 0.2 for Arba Minch University farmland, 0.4 & 0.25 for private farmland and 0.1 & 0.43 for Kollashara farmland, respectively. The value of irrigation equity was 0.7 in January, 0.6 in February, and 0.8 in March which indicates the highly temporary variation of irrigation adequacy. The mean value of canal conveyance was 82.7 % and the average on-farm irrigation efficiency also was 56.6 %. The average value crop yield in the present study were 0.5ton/ha for wheat, 4.9ton/ha for onion, 6.2ton/ha for pepper, 0.6ton/ha for watermelon, 4.2ton/ha for maize that was very low compared with other control irrigation in the study area. Inadequate soil moisture-based intervals, inequitable water distribution, and variable supply hinder irrigation in the Lower Kulfo catchment; adopting optimized practices and robust management can enhance efficiency, equity, and crop productivity.

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Objective: Oxidative stress develops because of a shift in the prooxidant-antioxidant balance toward the former, because of disturbances in redox signaling and control. Celecoxib (Cb), a selective COX-2 inhibitor, is a drug that effectively decreases pain and inflammation. However, Cb causes oxidative injury to hepatic tissues via enhanced lipid peroxidation, thus resulting in excessive production of reactive oxygen species. Consequently, frequent or long-term Cb use may lead to hepatic, renal, and other noticeable adverse effects. Lycopene (lyco), a potent antioxidant naturally occurring in pigmented fruits and vegetables, actively eradicates singlet oxygen and other free radicals, thereby protecting cells against destruction of the plasma membrane by free radicals. Methods: We hypothesized that lyco might protect rat liver cells against Cb-induced oxidative stress, thus reducing fatty infiltration and glycogen depletion. Rats were randomized into three groups (with ten rats each) receiving control (group A, saline only), Cb (group B, 50 mg/kg, orally), or Cb + lyco (group C, 50 mg/kg, orally) for 30 days. Subsequently, liver tissues were examined, and the average liver weight and histological changes in fat and glycogen content were determined. Results: Lyco mitigated hepatocyte damage in Cb-treated rats, reducing fat accumulation and glycogen loss, probably through its antioxidant properties. Concomitant lyco and Cb intake prevented hepatotoxic adverse effects due to oxidative injury, as well as non-alcoholic fatty liver disease (NAFLD), a key component of metabolic syndrome. Moreover, the binding orientation of lyco in the binding site of COX-2 enzyme revealed that the docked complex had noteworthy binding strength. Conclusion: In conclusion, our study revealed lyco's protective effects against Cb-induced hepatic damage by reducing fat and glycogen depletion.

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The current study investigated the effects of ego-depletion in junior high school students on displaced aggressive behavior and the counteraction of the nature. Study 1 investigated the effects of ego-depletion on displaced aggressive behavior in junior high school students using a within-subject design, comparing the differences in displaced aggressive behavior between the induced ego-depletion condition and the non-induced ego-depletion condition. Results showed that junior high school students exhibited significantly higher levels of displaced aggressive behavior under the induced ego-depletion condition compared to the non-induced ego-depletion condition. Study 2 examined the role of the nature in the process of ego-depletion influencing displaced aggressive behavior. A 2 (ego-depletion: induced ego-depletion vs. non-induced ego-depletion) × 2 (picture type: blank picture vs. natural picture) mixed design was used. A picture-viewing task was inserted between the ego-depletion task and the displaced aggressive behavior task to compare the differences in displaced aggressive behavior between the group that viewed blank pictures and the group that viewed natural pictures. The results showed that under the induced ego-depletion condition, there was no significant difference in displaced aggressive behavior between viewing natural pictures and viewing blank pictures. However, after viewing blank pictures, displaced aggressive behavior under induced ego-depletion condition was significantly higher than under non-induced ego-depletion condition; after viewing natural pictures, there was no significant difference in displaced aggressive behavior between induced ego-depletion condition and non-induced ego-depletion condition. These results suggest that ego-depletion can increase displaced aggressive behavior in junior high school students, but this phenomenon is not observed after exposure to nature. The current study provides empirical evidence for investigating the effects of ego-depletion on displaced aggressive behavior.

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Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G2-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl2-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.

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Cranial radiotherapy can cause lifelong cognitive complications in childhood brain tumor survivors, and reduced hippocampal neurogenesis is hypothesized to contribute to this. Following irradiation (IR), microglia clear dead neural progenitors and give rise to a neuroinflammatory microenvironment, which promotes a switch in surviving progenitors from neuronal to glial differentiation. Recently, depletion and repopulation of microglia were shown to promote neurogenesis and ameliorate cognitive deficits in various brain injury models. In this study, we utilized the Cx3cr1CreERt2-YFP/+Rosa26DTA/+ transgenic mouse model to deplete microglia in the juvenile mouse brain before subjecting them to whole-brain IR and investigated the short- and long-term effects on hippocampal neurogenesis. Within the initial 24 h after IR, the absence of microglia led to an accumulation of dead cells in the subgranular zone, and 50-fold higher levels of the chemokine C-C motif ligand 2 (CCL2) in sham brains and 7-fold higher levels after IR. The absence of microglia, and the subsequent repopulation within 10 days, did neither affect the loss of proliferating or doublecortin-positive cells, nor the reduced growth of the granule cell layer. Our results argue against a role for a pro-inflammatory microenvironment in the dysregulation of hippocampal neurogenesis and suggest that the observed reduction of neurogenesis was solely due to IR.

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ATTO 565, a Rhodamine-type dye, has garnered significant attention due to its remarkable optical properties, such as a high fluorescence quantum yield, and the fact that it is a relatively stable structure and has low biotoxicity. ATTO 565 has found extensive applications in combination with microscopy technology. In this review, the chemical and optical properties of ATTO 565 are introduced, along with the principles behind them. The functionality of ATTO 565 in confocal microscopy, stimulated emission depletion (STED) microscopy, single-molecule tracking (SMT) techniques, two-photon excitation-stimulated emission depletion microscopy (TPE-STED) and fluorescence correlation spectroscopy (FCS) is discussed. These studies demonstrate that ATTO 565 plays a crucial role in areas such as biological imaging and single-molecule localization, thus warranting further in-depth investigations. Finally, we present some prospects and concepts for the future applications of ATTO 565 in the fields of biocompatibility and metal ion detection. This review does not include theoretical calculations for the ATTO 565 molecule.

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Rituximab is recommended as the preferred second-line immunotherapy for autoimmune encephalitis (AE). However, Ofatumumab (OFA), a novel fully human anti-CD20 antibody, has been reported infrequently in patients with AE. Among the various forms of AE, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common and severe. This study presents three cases of severe anti-NMDAR encephalitis treated with OFA following the failure of first-line immunotherapy. The results indicated that the patients experienced no significant adverse reactions after receiving OFA, and their clinical symptoms improved markedly within one week of treatment. One month post-treatment with OFA, scores on the Glasgow Coma Scale (GCS) and the Barthel Index of Activities of Daily Living (Barthel-ADL) increased, while scores on the modified Rankin Scale (mRS), Clinical Assessment Scale in Autoimmune Encephalitis (CASE), and Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) decreased. During the three-month and six-month follow-up periods, patients exhibited further symptomatic improvement, suggesting that OFA is a safe and effective treatment option for anti-NMDAR encephalitis. These findings propose a novel therapeutic strategy for severe refractory anti-NMDAR encephalitis.

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Ego depletion theory proposes that self-regulation depends on a limited energy resource (willpower). The simple initial theory has been refined to emphasize conservation rather than resource exhaustion, extended to encompass decision making, planning, and initiative, and linked to physical bodily energy (glucose). Recent challenges offered alternative explanations (which have largely failed) and questioned replicability (which has now been well established). Methods have improved, particularly with emphasis on longer, stronger manipulations to ensure fatigue. New work extends ego depletion into workplace settings and sports. Interpersonal conflict may be both a major cause and consequence. New questions include the possibility of chronic ego depletion (e.g., in burnout), protective factors and coping strategies, individual differences, and recovery processes.

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Passive sampling techniques have undoubtedly proven effective for determining freely dissolved concentrations (Cfree) in sediment. However, the absence of a rationale-based, hands-on protocol for guiding practitioners in conducting ex situ exposure of passive samplers in sediment underscores the need for research and development in this area. The goal of this study was to address three critical issues for passive sampling in sediment ex situ: sediment dilution, depletion, and nonequilibrium. Polyethylene (PE) and polymethyl methacrylate (PMMA) film samplers were utilized in experiments involving hydrophobic organic compounds (HOCs, including PAHs, PCBs, PBDEs, and pesticides) spiked sediments. The results indicated that the influence of sediment dilution could be safely disregarded for HOCs with a larger Kd value (i.e., > 140) when moisture content of 80 % was selected for the exposure. Given some data deviations stemming from sample analysis, the depletion extent could significantly vary within a wide range (up to 36.4 %) rather than being fixed at a specific level (e.g., 5 %). Most HOCs reached equilibrium in a 10-d exposure for the PE sampler, and compounds with a log Kow value <7.12 did not need correction for nonequilibrium. An equation for estimating the nonequilibrium correction factor and an approach for correcting nonequilibrium exposure were introduced. The passive sampling method with PE was applied to a set of field-contaminated sediments under the depletion extents ranged from 7.1 % to 77 %. Based on the relatively comprehensive understanding of the passive sampling in sediment ex situ, a practical and standardized protocol was provided for Cfree measurement of HOCs.

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Over-exploitation of groundwater for irrigation caused rapid groundwater depletion in north India, leading to food and water security challenges. However, the crucial role of changing cropping patterns on groundwater savings under the observed and projected warming climate remains unexplored. Here, we show that altering the existing rice-dominated cropping systems in India can be a potential solution for groundwater sustainability under the current and future climate. Satellite and model-based estimates show that north India lost ∼336 and 297 km3 of groundwater, respectively during 2002-2022. We developed optimized crop switching scenarios for groundwater savings considering nutritional requirements, farmers' profit, and crop production. Crop switching considering all the three targets (crop switch one: CSI) and allowing rice replacement with alternate crops (crop switch two: CSII) could save 45 and 91 km3 groundwater, respectively in north India during the observed climate (2002-2022) compared with the current cropping pattern. Altering the current cropping pattern can lead to substantial groundwater savings under the projected future climate without comprising nutritional targets and farmers' profit at the state level. Replacing 37% area of rice with other crops (CSII) can recover 61 to 108 km3 groundwater compared with -13 to 43 km3 with current cropping pattern under the 1.5-3 °C global warming levels. Similarly, under the CSI scenario, 36 to 86 km3 groundwater can be recovered in the future warming world. Moreover, the benefits of crop switching in groundwater saving are higher during the prolonged dry periods compared with the baseline under the warming climate. Therefore, crop switching offers substantial benefits for groundwater sustainability under the current and projected future climate in India.

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Cold exposure therapy (CE), as an inexpensive method, has shown great potential in cancer therapy. Exploring the combined anti-tumor mechanism of CE and traditional therapies (such as photodynamic therapy (PDT)) is exciting and promising. Here, a bionic aggregation-induced emission photosensitizer system (named THL) is designed for combined CE to enhance anti-tumor immunotherapy. THL inherits the homologous targeting ability of tumor derived exosomes, promoting the enrichment of THL at the tumor site. Under external illumination, THL generates hydroxyl radicals and superoxide anions through type I PDT. In addition, mice are pretreated with cold exposure, which promotes THL mediated PDT and reactive oxygen species (ROS) generation by reducing the production of ATP and GSH in tumor tissue. This combination therapy increases production of ROS within the tumor, inhibits the growth of distant tumors, recurrent and rechallenged tumors and increases the number of cytotoxic CD8+T cells and memory T cells. Compared to PDT alone, combination therapy shows greater advantages in tumor immunotherapy. The combination therapy strategy provides new ideas for cancer immunotherapy.

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The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-based chemotherapy plus Gossypol with pro-apoptotic effects displays a synergistic effect for killing tumor cells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. In the patient-derived tumor xenograft (PDX) model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

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Bacterial shape and division rely on the dynamics of cell wall assembly, which involves regulated synthesis and cleavage of the peptidoglycan. In ovococci, these processes are coordinated within an annular mid-cell region with nanometric dimensions. More precisely, the cross-wall synthesized by the divisome is split to generate a lateral wall, whose expansion is insured by the insertion of the so-called peripheral peptidoglycan by the elongasome. Septum cleavage and peripheral peptidoglycan synthesis are, thus, crucial remodeling events for ovococcal cell division and elongation. The structural DivIVA protein has long been known as a major regulator of these processes, but its mode of action remains unknown. Here, we integrate click chemistry-based peptidoglycan labeling, direct stochastic optical reconstruction microscopy, and in silico modeling, as well as epifluorescence and stimulated emission depletion microscopy to investigate the role of DivIVA in Streptococcus pneumoniae cell morphogenesis. Our work reveals two distinct phases of peptidoglycan remodeling during the cell cycle that are differentially controlled by DivIVA. In particular, we show that DivIVA ensures homogeneous septum cleavage and peripheral peptidoglycan synthesis around the division site and their maintenance throughout the cell cycle. Our data additionally suggest that DivIVA impacts the contribution of the elongasome and class A penicillin-binding proteins to cell elongation. We also report the position of DivIVA on either side of the septum, consistent with its known affinity for negatively curved membranes. Finally, we take the opportunity provided by these new observations to propose hypotheses for the mechanism of action of this key morphogenetic protein.IMPORTANCEThis study sheds light on fundamental processes governing bacterial growth and division, using integrated click chemistry, advanced microscopy, and computational modeling approaches. It addresses cell wall synthesis mechanisms in the opportunistic human pathogen Streptococcus pneumoniae, responsible for a range of illnesses (otitis, pneumonia, meningitis, septicemia) and for one million deaths every year worldwide. This bacterium belongs to the morphological group of ovococci, which includes many streptococcal and enterococcal pathogens. In this study, we have dissected the function of DivIVA, which is a structural protein involved in cell division, morphogenesis, and chromosome partitioning in Gram-positive bacteria. This work unveils the role of DivIVA in the orchestration of cell division and elongation along the pneumococcal cell cycle. It not only enhances our understanding of how ovoid bacteria proliferate but also offers the opportunity to consider how DivIVA might serve as a scaffold and sensor for particular membrane regions, thereby participating in various cell cycle processes.

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Self-control is the ability to inhibit temptations and persist in one's decisions about what to do. In this article, we review recent evidence that suggests implicit beliefs about the process of self-control influence how the process operates. While earlier work focused on the moderating influence of willpower beliefs on depletion effects, we survey new directions in the field that emphasize how beliefs about the nature of self-control, self-control strategies, and their effectiveness have effects on downstream regulation and judgment. These new directions highlight the need to better understand the role of self-control beliefs in naturalistic decision-making.

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The overexpression of polyamines in tumor cells contributes to the establishment of immunosuppressive microenvironment and facilitates tumor growth. Here, it have ingeniously designed multifunctional copper-piceatannol/HA nanopills (Cu-Pic/HA NPs) that effectively cause total intracellular polyamines depletion by inhibiting polyamines synthesis, depleting intracellular polyamines, and impairing polyamines uptake, resulting in enhanced pyroptosis and cuproptosis, thus activating a powerful immune response to achieve anti-tumor therapy. Mitochondrial dysfunction resulting from overall intracellular polyamines depletion not only leads to the surge of copper ions in mitochondria, thereby causing the aggregation of toxic proteins to induce cuproptosis, but also triggers the accumulation of reactive oxygen species (ROS) within mitochondria, which further upregulates the expression of zDHHC5 and zDHHC9 to promote the palmitoylation of gasdermin D (GSDMD) and GSDMD-N, ultimately inducing enhanced pyroptosis. Then the occurrence of enhanced pyroptosis and cuproptosis is conductive to remodel the immunosuppressive tumor microenvironment, thus activating anti-tumor immune responses and ultimately effectively inhibiting tumor growth and metastasis. This therapeutic strategy of enhanced pyroptosis and cuproptosis through comprehensive polyamines depletion provides a novel template for cancer immunotherapy.