Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.

Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.

Past, present, and future of cell replacement therapy for parkinson's disease: a novel emphasis on host immune responses.

Parkinson's disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic (fVM) cells. Despite the initial favorable results, fVM cell therapy has intrinsic and logistical limitations that hinder its transition to a standard treatment for PD. Recent efforts in the field of cell therapy have shifted its focus towards the utilization of human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, to surmount existing challenges. However, regardless of the transplantable cell sources (e.g., xenogeneic, allogeneic, or autologous), the poor and variable survival of implanted dopamine cells remains a major obstacle. Emerging evidence highlights the pivotal role of host immune responses following transplantation in influencing the survival of implanted mDANs, underscoring an important area for further research. In this comprehensive review, building upon insights derived from previous fVM transplantation studies, we delve into the functional ramifications of host immune responses on the survival and efficacy of grafted dopamine cells. Furthermore, we explore potential strategic approaches to modulate the host immune response, ultimately aiming for optimal outcomes in future clinical applications of CRT for PD.

The complete mitochondrial genome of Hyperhalosydna striata (Kinberg, 1856) (Annelida: Polynoidae) collected from Jejudo Island, Korea.

The mitogenome sequence of Hyperhalosydna striata was determined for the first time in the present study. The genome is 15,226 bp long and contains 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), and 22 transfer RNA genes (tRNA). The overall base composition was 28.0% A, 21.9% C, 13.0% G, and 37.1% T. A phylogenetic tree was constructed to infer the phylogenetic position of H. striata among polynoid species whose mitochondrial genome sequences are available in GenBank. Hyperhalosydna striata was closely related to the species of subfamily Lepidonotinae.

Using wavelet transform and hybrid CNN - LSTM models on VOC & ultrasound IoT sensor data for non-visual maize disease detection.

Early detection of plant diseases is crucial for safeguarding crop yield, especially in regions vulnerable to food insecurity, such as Sub-Saharan Africa. One of the significant contributors to maize crop yield loss is the Northern Leaf Blight (NLB), which traditionally takes 14-21 days to visually manifest on maize. This study introduces a novel approach for detecting NLB as early as 4-5 days using Internet of Things (IoT) sensors, which can identify the disease before any visual symptoms appear. Utilizing Convolutional Neural Networks (CNN) and Long Short Term Memory (LSTM) models, nonvisual measurements of Total Volatile Organic Compounds (VOCs) and ultrasound emissions from maize plants were captured and analyzed. A controlled experiment was conducted on four maize varieties, and the data obtained were used to develop and validate a hybrid CNN-LSTM model for VOC classification and an LSTM model for ultrasound anomaly detection. The hybrid CNN-LSTM model, enhanced with wavelet data preprocessing, achieved an F1 score of 0.96 and an Area under the ROC Curve (AUC) of 1.00. In contrast, the LSTM model exhibited an impressive 99.98% accuracy in identifying anomalies in ultrasound emissions. Our findings underscore the potential of IoT sensors in early disease detection, paving the way for innovative disease prevention strategies in agriculture. Future work will focus on optimizing the models for IoT device deployment, incorporating chatbot technology, and more sensor data will be incorporated for improved accuracy and evaluation of the models in a field environment.

Paclitaxel and Carboplatin in Combination with Low-intensity Pulsed Ultrasound for Glioblastoma.

PURPOSE: We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control with paclitaxel at the maximal/target dose in our phase I trial (NCT04528680). To address this, we investigated the combination of paclitaxel with carboplatin in preclinical glioma models. EXPERIMENTAL DESIGN: We performed MRI-based analysis to evaluate disease control in patients from our trial. We studied the cytotoxicity of paclitaxel and carboplatin against 11 human glioma lines as monotherapy and in combination at concentrations derived from human intraoperative studies. Synergy was assessed with the Loewe model and the survival benefit evaluated in two xenografts. We examined the effects on cell cycle progression, DNA damage, and apoptosis. RESULTS: Patients treated with paclitaxel and LIPU/MB exhibited variable local tumor control, which correlated with overall survival. We observed limited cross-resistance to paclitaxel and carboplatin in glioma lines, with almost a third of them being exclusively susceptible to one drug. This combination led to susceptibility of 81% of lines and synergy in 55% of them. The combination proved more efficacious in two intracranial xenografts when administered with LIPU/MB, leading to complementary effects on cell cycle arrest. CONCLUSIONS: Combining paclitaxel and carboplatin in gliomas may be more efficacious than monotherapy, as in other cancers, due to synergy and independent susceptibility to each drug. These results form the basis for an ongoing phase II trial (NCT04528680) where we investigate this combination with LIPU/MB.

ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis.

PURPOSE: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts. EXPERIMENTAL DESIGN: In a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and OS. Patients received intravenous nivolumab, followed by maximal safe resection and an intracerebral injection of either ipilimumab alone or combined with nivolumab. Biweekly adjuvant nivolumab was then administered up to five times (NCT03233152). Using REporting recommendations for tumor MARKER prognostic studies (REMARK) criteria, we conducted independent analyses for p-ERK quantification and statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models and meta-analysis were employed to assess p-ERK as a predictive biomarker after immunotherapy. RESULTS: Lower median p-ERK+ cell density was observed compared with prior studies, likely due to variable tissue processing across cohorts. Nonetheless, high p-ERK was associated with prolonged OS, particularly in isocitrate dehydrogenase wild-type glioblastomas (P = 0.036). Median OS for high and low p-ERK patients were 55.6 and 30 weeks, respectively. Multivariable analysis reinforced p-ERK's significance in survival prediction (P = 0.011). Upon p-ERK normalization across cohorts (n = 65), meta-analysis supported the survival benefit of elevated tumor p-ERK levels (P = 0.0424). CONCLUSIONS: This study strengthens the role of p-ERK as a predictive biomarker for OS in patients with glioblastoma on immune checkpoint blockade. Future research should focus on further validation in prospective trials and the standardization of preanalytical variables influencing p-ERK quantification.

An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.

The nuclear receptor, Nurr1, is critical for both the development and maintenance of midbrain dopamine neurons, representing a promising molecular target for Parkinson's disease (PD). We previously identified three Nurr1 agonists (amodiaquine, chloroquine and glafenine) that share an identical chemical scaffold, 4-amino-7-chloroquinoline (4A7C), suggesting a structure-activity relationship. Herein we report a systematic medicinal chemistry search in which over 570 4A7C-derivatives were generated and characterized. Multiple compounds enhance Nurr1's transcriptional activity, leading to identification of an optimized, brain-penetrant agonist, 4A7C-301, that exhibits robust neuroprotective effects in vitro. In addition, 4A7C-301 protects midbrain dopamine neurons in the MPTP-induced male mouse model of PD and improves both motor and non-motor olfactory deficits without dyskinesia-like behaviors. Furthermore, 4A7C-301 significantly ameliorates neuropathological abnormalities and improves motor and olfactory dysfunctions in AAV2-mediated α-synuclein-overexpressing male mouse models. These disease-modifying properties of 4A7C-301 may warrant clinical evaluation of this or analogous compounds for the treatment of patients with PD.

Zinc-aluminum layered double hydroxide and double oxide for room-temperature oxidation of sulfur dioxide gas.

Sulfur dioxide (SO2) gas at trace levels challenges the consumption of fuel gases and cleaning of flue gases originating from diverse anthropogenic sources. We have demonstrated Zn-Al layered double hydroxide (LDH) and layered double oxide (LDO) as low-cost and effective adsorbents in removing lowly concentrated SO2 gas at room temperature. Water in the adsorbent bed significantly improved the performance, where the maximum adsorption capacity of 38.0 mg g-1 was achieved for LDO. Based on the spectroscopic findings, the adsorbed gas molecules were oxidized to surface-bound sulfate/bisulfate species, showing complete mineralization of SO2 molecules. By employing an inexpensive NaOH-H2O2 solution-based regeneration strategy, we successfully regenerated the spent LDO, significantly restoring its gas uptake capacity. The regenerated oxide exhibited an increased gas uptake capacity ranging from 38.0 to 98.5 mg g-1, highlighting the practicality and economic feasibility of our approach. LDH/LDO materials are promising regenerable adsorbents for removing low concentrations of SO2 gas in ambient conditions.

Co-transplantation of autologous Treg cells in a cell therapy for Parkinson's disease.

The specific loss of midbrain dopamine neurons (mDANs) causes major motor dysfunction in Parkinson's disease, which makes cell replacement a promising therapeutic approach1-4. However, poor survival of grafted mDANs remains an obstacle to successful clinical outcomes5-8. Here we show that the surgical procedure itself (referred to here as 'needle trauma') triggers a profound host response that is characterized by acute neuroinflammation, robust infiltration of peripheral immune cells and brain cell death. When midbrain dopamine (mDA) cells derived from human induced pluripotent stem (iPS) cells were transplanted into the rodent striatum, less than 10% of implanted tyrosine hydroxylase (TH)+ mDANs survived at two weeks after transplantation. By contrast, TH- grafted cells mostly survived. Notably, transplantation of autologous regulatory T (Treg) cells greatly modified the response to needle trauma, suppressing acute neuroinflammation and immune cell infiltration. Furthermore, intra-striatal co-transplantation of Treg cells and human-iPS-cell-derived mDA cells significantly protected grafted mDANs from needle-trauma-associated death and improved therapeutic outcomes in rodent models of Parkinson's disease with 6-hydroxydopamine lesions. Co-transplantation with Treg cells also suppressed the undesirable proliferation of TH- grafted cells, resulting in more compact grafts with a higher proportion and higher absolute numbers of TH+ neurons. Together, these data emphasize the importance of the initial inflammatory response to surgical injury in the differential survival of cellular components of the graft, and suggest that co-transplanting autologous Treg cells effectively reduces the needle-trauma-induced death of mDANs, providing a potential strategy to achieve better clinical outcomes for cell therapy in Parkinson's disease.

Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade.

Whereas the contribution of tumor microenvironment to the profound immune suppression of glioblastoma (GBM) is clear, tumor-cell intrinsic mechanisms that regulate resistance to CD8 T cell mediated killing are less understood. Kinases are potentially druggable targets that drive tumor progression and might influence immune response. Here, we perform an in vivo CRISPR screen to identify glioma intrinsic kinases that contribute to evasion of tumor cells from CD8 T cell recognition. The screen reveals checkpoint kinase 2 (Chek2) to be the most important kinase contributing to escape from CD8 T-cell recognition. Genetic depletion or pharmacological inhibition of Chek2 with blood-brain-barrier permeable drugs that are currently being evaluated in clinical trials, in combination with PD-1 or PD-L1 blockade, lead to survival benefit in multiple preclinical glioma models. Mechanistically, loss of Chek2 enhances antigen presentation, STING pathway activation and PD-L1 expression in mouse gliomas. Analysis of human GBMs demonstrates that Chek2 expression is inversely associated with antigen presentation and T-cell activation. Collectively, these results support Chek2 as a promising target for enhancement of response to immune checkpoint blockade therapy in GBM.

Peroxiredoxin 5 regulates osteogenic differentiation through interaction with hnRNPK during bone regeneration.

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.

Novel application of sodium manganese oxide in removing acidic gases in ambient conditions.

In this study, we have demonstrated the application of sodium manganese oxide for the chemisorption of toxic acidic gases at room temperature. The fabricated alkali ceramic has Na0.4MnO2, Na2Mn3O7, and NaxMnO2 phases with a surface area of 2.6 m2 g-1. Na-Mn oxide was studied for oxidation of H2S, SO2, and NO2 gases in the concentration range of 100-500 ppm. The material exhibited a high uptake capacity of 7.13, 0.75, and 0.53 mmol g-1 for H2S, SO2, and NO2 in wet conditions, respectively. The material was reusable when regenerated simply by soaking the spent oxide in a NaOH-H2O2 solution. While the H2S chemisorption process was accompanied by sulfide, sulfur, and sulfate formation, the SO2 chemisorption process yielded only sulfate ions. The NO2 chemisorption process was accomplished by its conversion to nitrite and nitrate ions. Thus, the present work is one of the first reports on alkali ceramic utilization for room-temperature mineralization of acidic gases.

Current Status and Future Perspectives on Stem Cell-Based Therapies for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1%-2% of the population over the age of 65. As the population ages, it is anticipated that the burden on society will significantly escalate. Although symptom reduction by currently available pharmacological and/or surgical treatments improves the quality of life of many PD patients, there are no treatments that can slow down, halt, or reverse disease progression. Because the loss of a specific cell type, midbrain dopamine neurons in the substantia nigra, is the main cause of motor dysfunction in PD, it is considered a promising target for cell replacement therapy. Indeed, numerous preclinical and clinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells remains fraught with controversy due to fundamental ethical, practical, and clinical limitations. Groundbreaking work on human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, coupled with extensive basic research in the stem cell field offers promising potential for hPSC-based cell replacement to become a realistic treatment regimen for PD once several major issues can be successfully addressed. In this review, we will discuss the prospects and challenges of hPSC-based cell therapy for PD.

A Novel Metal-Containing Mesoporous Silica Composite for the Decolorization of Rhodamine B: Effect of Metal Content on Structure and Performance.

A series of novel MnxFey@SiO2 (x,y = 1-20%) nanocomposites were synthesized for the first time via the sol-gel/combustion method with different content of precursors (Mn and Fe acetate salts). The effect of precursor content and ratio on physicochemical properties were observed by various characterization methods. Moreover, Rhodamine B (RhB) was chosen as the target pollutant to test the performance of these nanocomposites under a photocatalytic Fenton-like reaction. The results showed that the nanocomposite morphology improved by increasing Fe and Mn content. In this study, interesting behavior was observed in BET results which were different from the fact that increasing metal content can decrease the surface area. This study revealed that one metal could be more critical in controlling the properties than another. Moreover, the precursor ratio appears to have a more tangible effect on the surface area than the effect of precursor content. Among all synthesized nanocomposites, Mn1Fe5@SiO2 showed the highest surface area of 654.95 m2/g. At optimum batch conditions (temp = 25 °C, catalyst dosage = 1 g L-1, H2O2 = 75 mmolL-1, and initial RhB concentration = 50 mg L-1), complete removal (simultaneous adsorption/degradation) occurred using Mn1Fe5@SiO2 at neutral pH. This study showed that the designed nanomaterial could be used as a dual functional adsorbent/photocatalyst in different environmental applications.

Sustainable Removal of BTEX Gas Using Regenerated Metal Containing SiO2.

In the last decades, the removal of benzene, toluene, ethylbenzene, and xylene (BTEX) has been considered a major environmental crisis. In this study, two novel nanocomposite materials (Fe2O3/SiO2 and Fe2O3-Mn2O3/SiO2) that have regeneration ability by UV irradiation have been fabricated to remove BTEX at ambient temperature. This research revealed that both nanocomposites could remove more than 85% of the BTEX in the first cycle. The adsorption capacities followed the order of ethylbenzene > m-xylene > toluene > benzene as in the molecular weight order. The reusability test using UV irradiation showed that the performance of Fe2O3/SiO2 decreased drastically after the fifth cycle for benzene. On the other hand, when Mn is located in the nanocomposite structure, Fe2O3-Mn2O3/SiO2 could maintain its adsorption performance with more than 80% removal efficiency for all the BTEX for ten consecutive cycles. The difference in the reusability of the two nanocomposites is that the electron energy (from the valence band to the conduction band) for BTEX decomposition is changed due to the presence of manganese. This study provides a promising approach for designing an economical reusable nanomaterial, which can be used for VOC-contaminated indoor air.

Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer effects through miRNA delivery.

T cell-derived small extracellular vesicles (sEVs) exhibit anti-cancer effects. However, their anti-cancer potential should be reinforced to enhance clinical applicability. Herein, we generated interleukin-2-tethered sEVs (IL2-sEVs) from engineered Jurkat T cells expressing IL2 at the plasma membrane via a flexible linker to induce an autocrine effect. IL2-sEVs increased the anti-cancer ability of CD8+ T cells without affecting regulatory T (Treg ) cells and down-regulated cellular and exosomal PD-L1 expression in melanoma cells, causing their increased sensitivity to CD8+ T cell-mediated cytotoxicity. Its effect on CD8+ T and melanoma cells was mediated by several IL2-sEV-resident microRNAs (miRNAs), whose expressions were upregulated by the autocrine effects of IL2. Among the miRNAs, miR-181a-3p and miR-223-3p notably reduced the PD-L1 protein levels in melanoma cells. Interestingly, miR-181a-3p increased the activity of CD8+ T cells while suppressing Treg cell activity. IL2-sEVs inhibited tumour progression in melanoma-bearing immunocompetent mice, but not in immunodeficient mice. The combination of IL2-sEVs and existing anti-cancer drugs significantly improved anti-cancer efficacy by decreasing PD-L1 expression in vivo. Thus, IL2-sEVs are potential cancer immunotherapeutic agents that regulate both immune and cancer cells by reprogramming miRNA levels.

Fabrication of Na0.4MnO2 Microrods for Room-Temperature Oxidation of Sulfurous Gases.

Phase pure Na0.4MnO2 microrods crystallized in the orthorhombic symmetry were fabricated for the wet oxidation of H2S and SO2 gases at room temperature. The material was found highly effective for the mineralization of low concentrations of acidic gases. The material was fully regenerable after soaking in a basic H2O2 solution.

Ternary metal oxide nanocomposite for room temperature H2S and SO2 gas removal in wet conditions.

A ternary Mn-Zn-Fe oxide nanocomposite was fabricated by a one-step coprecipitation method for the remotion of H2S and SO2 gases at room temperature. The nanocomposite has ZnO, MnO2, and ferrites with a surface area of 21.03 m2 g-1. The adsorbent was effective in mineralizing acidic sulfurous gases better in wet conditions. The material exhibited a maximum H2S and SO2 removal capacity of 1.31 and 0.49 mmol g-1, respectively, in the optimized experimental conditions. The spectroscopic analyses confirmed the formation of sulfide, sulfur, and sulfite as the mineralized products of H2S. Additionally, the nanocomposite could convert SO2 to sulfate as the sole oxidation by-product. The oxidation of these toxic gases was driven by the dissolution and dissociation of gas molecules in surface adsorbed water, followed by the redox behaviour of transition metal ions in the presence of molecular oxygen and water. Thus, the study presented a potential nanocomposite adsorbent for deep desulfurization applications.

Probing the origin and stability of bivalency in copper based porous coordination network and its application for H2S gas capture.

A bivalent Cu(I,II) metal-organic framework (MOF) based on the 4,4',4″-s-Triazine-2,4,6-triyl-tribenzoate linker was synthesized via a solvothermal method. The MOF possessed 43.8% of the Cu sites as Cu+ with a surface area of 1257 m2 g-1. The detailed spectroscopic analysis confirmed dimethylformamide (DMF) solvent as the reductant responsible for Cu+ sites in the synthesized MOF. The Cu+ sites were easily accessible and prone to oxidation in hot water or acidic gas environment. The MOF showed water-induced structural change, which could be partially recovered after soaking in DMF solvent. The synthesized MOF showed a high hydrogen sulfide (H2S) uptake capacity of 4.3 mmol g-1 at 298 K and an extremely low H2S pressure of 0.0005 bar. The adsorption capacity was the highest among Cu-based MOFs with PCN-6-M being regenerable, which made it useful for deep desulfurization applications. The adsorbed H2S was mineralized to sulfide, sulfur, and sulfates, mediated by the Cu+/Cu2+ redox cycle in the presence of adsorbed water and molecular oxygen. Thus, the study confirmed that DMF as a reductant is responsible for the origin of bivalency in PCN-6-M and possibly in other Cu-based MOFs reported in the literature. Also, the developed MOF could be a potential candidate for flue gas desulfurization and gas purification applications.

Enhanced natural killer cell anti-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer.

Ferroptosis provides an opportunity to overcome the cancer cell therapeutic resistance and modulate the immune system. Here an interaction between ferroptosis of cancer cells and natural killer (NK) cells was investigated with a clinical grade iron oxide nanoparticle (ferumoxytol) for potential synergistic anti-cancer effect of ferroptosis and NK cell therapy in prostate cancer. When ferumoxytol mediated ferroptosis of cancer cells was combined with NK cells, the NK cells' cytotoxic function was increased. Observed ferroptosis mediated NK cell activation was also confirmed with IFN-γ secretion and lytic degranulation. Upregulation of ULBPs, which is one of the ligands for NK cell activating receptor NKG2D, was observed in the co-treatment of ferumoxytol mediated ferroptosis and NK cells. Additionally, HMGB1 and PD-L1 expression of cancer cells were observed in the treatment of ferroptosis + NK cells. Finally, in vivo therapeutic efficacy of ferumoxytol mediated ferroptosis and NK cell therapy was observed with significant tumor volume regression in a prostate cancer mice model. These results suggest that the NK cells' function can be enhanced with ferumoxytol mediated ferroptosis.