Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering.

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Photopolymerizable and Antibacterial Hydrogels Loaded with Metabolites from Lacticaseibacillus rhamnosus GG for Infected Wound Healing.

In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.

Robot-assisted Percutaneous Radiofrequency Ablation for the Treatment of Osteoid Osteomas.

OBJECTIVE: Percutaneous CT-guided radiofrequency ablation (CT-RFA) is a widely accepted procedure for treatment of osteoid osteomas. However, the application of CT-RFA was restricted as a result of some drawbacks, such as radiation exposure, and inconvenience in general anesthesia. The primary aim of this study is to evaluate the safety and efficacy of intra-operative TiRobot-assisted percutaneous RFA of osteoid osteomas. METHODS: We retrospectively reviewed 21 medical files of patients who were treated with percutaneous RFA of osteoid osteomas guided by the TiRobot system in our institution between March 2021 and April 2022. The three-dimensional images obtained by a 3D C-arm intra-operatively were sent to the TiRobot system. The puncture point and trajectory were designed. Then the guide pin was positioned to the lesion with the assistance of TiRobot and the biopsy sheath was inserted into the lesion through the guide pin. The tumor was biopsied for pathological examination. Then the RFA needle was inserted into the nidus through the biopsy sheath for thermal ablation. Data were extracted on the associated complications, the reduction in pain at 1 month and 1 year postoperatively assessed by the visual analogue scale (VAS). A paired t-test was used to compare the pre-operative and post-operative VAS scores. RESULTS: The patients included 17 males and four females with a mean age of 19.5 ± 10.4 years (range 3-45 years). Lesions were located on the femur in nine cases, on the tibia in nine cases, on the humerus in one case, on the calcaneus in one case, and on the acetabulum in one case. TiRobot-assisted percutaneous RFA was successfully performed on all 21 patients. There was no intra-operative or post-operative complications observed. Pathological diagnosis of osteoid osteoma was obtained in 11 patients, but the other 10 cases were not pathologically diagnosed. The mean follow-up time was 18.8 months (range: 12-26 months).Post-operative VAS scores were reduced significantly in all cases. The mean VAS score decreased from 6.5 pre-operatively to 0.5 at 1 month post-operatively and to 0.1 at 1 year post-operatively. CONCLUSION: As a reliable technique for localizing and resection of nidus, TiRobot-assisted percutaneous RFA is a safe and effective option for the treatment of osteoid osteomas.

cGAS-STING, an important signaling pathway in diseases and their therapy.

Since cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS-STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS-STING plays a key role in human diseases, particularly DNA-triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation-related diseases. Here, we aim to summarize the ancient origin of the cGAS-STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS-STING. We will also focus on the important roles of cGAS-STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS-STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS-STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS-STING, provide a theoretical basis for further exploration of the roles of cGAS-STING in diseases, and open up new strategies for targeting cGAS-STING as a promising therapeutic intervention in multiple diseases.

Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study.

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.

Oxygen-supplying ROS-responsive prodrug for synergistic chemotherapy and photodynamic therapy of colon cancer.

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

A controlled light-induced gas-foaming porous hydrogel with adhesion property for infected wound healing.

Porous hydrogels as scaffolds have great potential in tissue engineering. However, there are still challenges in preparing porous hydrogels with tunable pore size and controlled porosity. Here, we successfully established a photoinduced gas-foaming method of porous hydrogels with controlled macro-micro-nano multiscale. A diazirine (DZ)-modified gelatin (GelDZ) biomaterial was prepared by introducing photocrosslinked DZ group into gelatin. Upon exposure to 365 nm UV light, DZ could be converted to the active group carbene, which could randomly insert into OH, NH, or CH bonds to form covalent crosslinks. GelDZ generated N2 by photodegradation and formed gas-induced porous hydrogels by intermolecular crosslinking without initiator. The loose porous structure of the hydrogel can promote the infiltration of host cells and blood vessels, which was conducive to tissue repair. The interfacial crosslinking of photoactivated GelDZ with tissue proteins imparted adhesion properties to the hydrogel. GelDZ also possessed photoreduction ability, which can reduce silver ions from metal precursors to silver nanoparticles (Ag NPs) in situ, and showed great antibacterial activity due to the sustained release of Ag NPs. GelDZ-Ag NPs prepared by in situ photoreaction can effectively inhibit wound infection and promote skin wound healing, providing a new strategy for designing porous hydrogel in tissue engineering.

Quality Evaluation of Metabolic-Associated Fatty Liver Disease Guidelines and Expert Consensus.

The purpose of this study is to evaluate and analyze the quality of guidelines and expert consensus on clinical practice regarding metabolically associated fatty liver disease (MAFLD) over the past five years. Data from the websites were retrieved using computers. We evaluated guidelines and expert consensus on MAFLD that were officially published between January 1, 2018 and March 24, 2023. Two evaluators independently examined the literature and extracted data. The included literature on guidelines and expert consensus was then subjected to quality review and analysis using assessment tools from Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) (2016). The intraclass correlation coefficient (ICC) values of all items on the AGREE II scale for the two evaluators were greater than 0.75, indicating a high degree of agreement between their assessments. Scope and purpose (48.90%), participants (49.21%), rigor in the formulation process (56.97%), clarity of expression (90.08%), applicability (66.08%), and independence of file compiling (60.12%) were the AGREE II scoring items with the standardized average scores. Apart from the participants, the average scores of all the scoring items in the guidelines from other countries other than China were higher than those from China (|Z|+>+2.272, p+<+0.05). MAFLD guidelines must be revised to enhance their methodological quality. When creating guidelines, it is recommended that the formulators strictly adhere to the formulation and drafting standards of AGREE II and elevate the quality of the guidelines.

Accelerated Diffusion of a Copper(I)-Functionalized COF Packed Bed Reactor for Efficient Continuous Flow Catalysis.

Flow chemistry provides a neo-orientation for the research and development of chemical technology, in which heterogeneous continuous catalysis based on packed beds can realize rapid separation and recycling. However, options for heterogeneous catalysts are still limited. In this work, we gradually grow covalent organic frameworks (COFs, TpBpy) on the surface of a silica gel (SiO2)-supported substrate to obtain a stable copper(I)-chelated high-loading heterogeneous catalyst (SiO2@CuI-TpBpy). SiO2@CuI-TpBpy shows high catalytic activity in three-component Huisgen 1,3-dipolar cycloaddition, giving the corresponding triazoles with excellent yields and reposeful recyclability under batch conditions. The structures of the catalysts remain steady, and the copper contents are basically unchanged after five cycles. Then, the catalysts are successfully applied for three-component heterogeneous catalysis in a one-pot continuous flow to prepare rufinamide in 89% yield for 24 h stably and efficiently with mere traces of copper ions remaining. More importantly, the catalytic system reveals a minuscule effect of catalyst particle size on internal diffusion. This COF encapsulation strategy presents a new possibility for the design of industrial heterogeneous catalysts with high metal loading and low internal diffusion resistance.

Green preparation of antibacterial shape memory foam based on bamboo cellulose nanofibril and waterborne polyurethane for adaptive relief of plantar pressure.

This study developed an aqueous solution blending and freeze-drying method to prepare an antibacterial shape memory foam (WPPU/CNF) based on waterborne PHMG-polyurethane and cellulose nanofibers derived from bamboo in response to the increasing demand for environmentally friendly, energy conserving, and multifunctional foams. The obtained WPPU/CNF composite foam has a highly porous network structure with well-dispersed CNFs forming hydrogen bonds with the WPPU matrix, which results in a stable and rigid cell skeleton with enhanced mechanical properties (80 KPa) and anti-abrasion ability. The presence of guanidine in the polyurethane chain endowed the WPPU/CNF composite foam with an instinctive and sustained antibacterial ability against Escherichia coli and Staphylococcus aureus. The WPPU/CNF composite foam exhibited a water-sensitive shape memory function in a cyclic shape memory program because of the chemomechanical adaptability of the hydrogen-bonded network of CNFs in the elastomer matrix. The shape-fixation ratio for local compression reached 95 %, and the shape-recovery rate reached 100 %. This allows the WPPU/CNF pad prototype to reversibly adjust the undulation height to adapt to plantar ulcers, which can reduce the local plantar pressure by 60 %. This study provides an environmentally friendly strategy for cellulose-based composite fabrication and enriches the design and application of intelligent foam devices.

General requirements for the production of extracellular vesicles derived from human stem cells.

'General requirements for the production of extracellular vesicles derived from human stem cells' is the first guideline for stem cells derived extracellular vesicles in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the general requirements, process requirements, packaging and labelling requirements and storage requirements for preparing extracellular vesicles derived from human stem cells, which is applicable to the research and production of extracellular vesicles derived from stem cells. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardisation of extracellular vesicles derived from human stem cells.

Technical specifications for ethics review of human stem cell research.

The rapid advancement of human stem cell research and its expansion into emerging areas has resulted in an escalation of ethical challenges associated with these studies. As a result, there has been a corresponding increase in both the volume and complexity of institutional ethics reviews, coupled with higher expectations for the quality of the review process. In response to these challenges, this standard provides a comprehensive outline of the fundamental principles, content, types, and procedures of ethics review, specifically focusing on non-clinical human stem cell research. Its purpose is to provide clear operational and procedural guidelines, as well as recommendations, for the ethics review of such studies. The document was originally published by the Chinese Society for Cell Biology on August 30, 2022. It is our hope that the publication of these guidelines will facilitate the integration of ethical considerations and evaluations in a structured manner throughout the entire process of stem cell research, ultimately fostering a healthy and orderly development of the field.

Quality appraisal of clinical practice guidelines for the management of Dysphagia after acute stroke.

Objectives: Dysphagia is a common complication in stroke patients, widely affecting recovery and quality of life after stroke. The objective of this systematic review is to identify the gaps that between evidence and practice by critically assessing the quality of clinical practice guidelines (CPGs) for management of dysphagia in stroke. Methods: We systematically searched academic databases and guideline repositories between January 1, 2014, and August 1, 2023. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used by two authors to independently assess CPG quality. Results: In a total of 14 CPGs included, we identified that three CPGs obtained a final evaluation of "high quality," nine CPGs achieved "moderate quality" and two CPGs received "low quality." The domain of "scope and purpose" achieved the highest mean score (91.1%) and the highest median (IQR) of 91.7% (86.1, 94.4%), while the domain of "applicability" received the lowest mean score (55.8%) and the lowest median (IQR) of 55.4% (43.2, 75.5%). Conclusion: The CPG development group should pay more attention to improving the methodological quality according to the AGREE II instrument, especially in the domain of "applicability" and "stakeholder involvement;" and each item should be refined as much as possible.

Virtual Reality in Clinical Nursing Practice Over the Past 10 Years: Umbrella Review of Meta-Analyses.

Background: Virtual reality (VR) has shown promising levels of effectiveness in nursing education, pain management, and rehabilitation. However, meta-analyses have discussed the effects of VR usage in nursing unilaterally and inconsistently, and the evidence base is diffuse and varied. Objective: We aimed to synthesize the combined evidence from meta-analyses that assessed the effects of nurses using VR technology on nursing education or patient health outcomes. Methods: We conducted an umbrella review by searching for meta-analyses about VR intervention in clinical nursing practice on Web of Science, Embase, Cochrane, and PubMed, and in reference lists. Eligible studies were published in English between December 1, 2012, and September 20, 2023. Meta-analyses of ≤2 intervention studies and meta-analyses without 95% CI or heterogeneity data were excluded. Characteristic indicators, population information, VR intervention information, and 95% CIs were extracted. A descriptive analysis of research results was conducted to discern relationships between VR interventions and outcomes. I2 and P values were used to evaluate publication bias. AMSTAR (A Measurement Tool to Assess Systematic Reviews) 2 and the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) checklist were used to appraise literature quality. Results: In total, 768 records were identified; 74 meta-analyses were included for review. The most reported VR study conditions were neuronursing (25/74, 34%), pediatric nursing (13/74, 18%), surgical and wound care (11/74, 15%), oncological nursing (11/74, 15%), and older adult nursing (10/74, 14%). Further, 30% (22/74) of meta-analyses reported publication bias, and 15% (11/74) and 8% (6/74) were rated as "high" based on AMSTAR 2 and the GRADE checklist, respectively. The main outcome indicators among all included meta-analyses were pain (37/214, 17.3%), anxiety (36/214, 16.8%), cognitive function (17/214, 7.9%), balance (16/214, 7.5%), depression (16/214, 7.5%), motor function (12/214, 5.6%), and participation in life (12/214, 5.6%). VR treatment for cognition, pain, anxiety, and depression was effective (all P values were <.05), while the utility of VR for improving motor function, balance, memory, and attention was controversial. Adverse effects included nausea, vomiting, and dizziness (incidence: range 4.76%-50%). The most common VR platforms were Pico VR glasses, head-mounted displays, the Nintendo Wii, and the Xbox Kinect. VR intervention duration ranged from 2 weeks to 12 months (typically ≥4 wk). VR session length and frequency ranged from 5 to 100 minutes and from 1 to 10 times per week, respectively. Conclusions: VR in nursing has positive effects-relieving patients' pain, anxiety, and depression and improving cognitive function-despite the included studies' limited quality. However, applying VR in nursing to improve patients' motor function, balance, memory, and attention remains controversial. Nursing researchers need to further explore the effects and standard operation protocols of VR in clinical practice, and more high-quality research on VR in nursing is needed.

Does postoperative pulmonary infection correlate with intestinal flora following gastric cancer surgery? - a nested case-control study.

Introduction: The primary objective of this study was to investigate the potential correlation between gut microbes and postoperative pulmonary infection in gastric cancer patients. Additionally, we aimed to deduce the mechanism of differential functional genes in disease progression to gain a better understanding of the underlying pathophysiology. Methods: A nested case-control study design was utilized to enroll patients with gastric cancer scheduled for surgery at West China Hospital of Sichuan University. Patients were categorized into two groups, namely, the pulmonary infection group and the control group, based on the development of postoperative pulmonary infection. Both groups were subjected to identical perioperative management protocols. Fecal samples were collected 24 h postoperatively and upon pulmonary infection diagnosis, along with matched controls. The collected samples were subjected to 16S rDNA and metagenomic analyses, and clinical data and blood samples were obtained for further analysis. Results: A total of 180 fecal specimens were collected from 30 patients in both the pulmonary infection and control groups for 16S rDNA analysis, and 3 fecal samples from each group were selected for metagenomic analysis. The study revealed significant alterations in the functional genes of the intestinal microbiome in patients with postoperative pulmonary infection in gastric cancer, primarily involving Klebsiella, Enterobacter, Ruminococcus, and Collinsella. During postoperative pulmonary infection, gut flora and inflammatory factors were found to be associated with the lipopolysaccharide synthesis pathway and short-chain fatty acid (SCFA) synthesis pathway. Discussion: The study identified enriched populations of Klebsiella, Escherella, and intestinal bacteria during pulmonary infection following gastric cancer surgery. These bacteria were found to regulate the lipopolysaccharide synthesis pathway, contributing to the initiation and progression of pulmonary infections. Inflammation modulation in patients with postoperative pulmonary infection may be mediated by short-chain fatty acids. The study also revealed that SCFA synthesis pathways were disrupted, affecting inflammation-related immunosuppression pathways. By controlling and maintaining intestinal barrier function, SCFAs may potentially reduce the occurrence of pulmonary infections after gastric cancer surgery. These findings suggest that targeting the gut microbiome and SCFA synthesis pathways may be a promising approach for preventing postoperative pulmonary infections in gastric cancer patients.

Emerging trends and focus of research on the relationship between traumatic brain injury and gut microbiota: a visualized study.

Background: Traumatic brain injury (TBI) is one of the most serious types of trauma and imposes a heavy social and economic burden on healthcare systems worldwide. The development of emerging biotechnologies is uncovering the relationship between TBI and gut flora, and gut flora as a potential intervention target is of increasing interest to researchers. Nevertheless, there is a paucity of research employing bibliometric methodologies to scrutinize the interrelation between these two. Therefore, this study visualized the relationship between TBI and gut flora based on bibliometric methods to reveal research trends and hotspots in the field. The ultimate objective is to catalyze progress in the preclinical and clinical evolution of strategies for treating and managing TBI. Methods: Terms related to TBI and gut microbiota were combined to search the Scopus database for relevant documents from inception to February 2023. Visual analysis was performed using CiteSpace and VOSviewer. Results: From September 1972 to February 2023, 2,957 documents published from 98 countries or regions were analyzed. The number of published studies on the relationship between TBI and gut flora has risen exponentially, with the United States, China, and the United Kingdom being representative of countries publishing in related fields. Research has formed strong collaborations around highly productive authors, but there is a relative lack of international cooperation. Research in this area is mainly published in high-impact journals in the field of neurology. The "intestinal microbiota and its metabolites," "interventions," "mechanism of action" and "other diseases associated with traumatic brain injury" are the most promising and valuable research sites. Targeting the gut flora to elucidate the mechanisms for the development of the course of TBI and to develop precisely targeted interventions and clinical management of TBI comorbidities are of great significant research direction and of interest to researchers. Conclusion: The findings suggest that close attention should be paid to the relationship between gut microbiota and TBI, especially the interaction, potential mechanisms, development of emerging interventions, and treatment of TBI comorbidities. Further investigation is needed to understand the causal relationship between gut flora and TBI and its specific mechanisms, especially the "brain-gut microbial axis."

Eicosapentaenoic acid enhances the sensitivity of osteosarcoma to cisplatin by inducing ferroptosis through the DNA-PKcs/AKT/NRF2 pathway and reducing PD-L1 expression to attenuate immune evasion.

Acquired drug resistance poses a significant challenge in osteosarcoma therapy. Therefore, it is necessary for us to discover and develop an alternative anti-cancer strategy. Previous studies have shown that eicosapentaenoic acid (EPA) significantly increases chemosensitivity in cancer cells. In this study, we discovered that EPA enhances the sensitivity of osteosarcoma to cisplatin (DDP). Interestingly, in addition to inhibiting growth and inducing apoptosis, EPA also enhances DDP-induced ferroptosis. Western blot analysis confirmed that EPA treatment significantly decreases the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), p-AKT, nuclear factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) in cells. Knockdown of DNA-PKcs by siRNA further enhances the level of ferroptosis induced by EPA. Importantly, EPA can reverse the high expression level of programmed death ligand 1 (PD-L1) induced by DDP. ELISA and western blotting analysis revealed that EPA treatment decreases the levels of IL-6 and p-STAT3, which are increased by DDP treatment. Furthermore, a co-immunoprecipitation (co-IP) assay confirmed the interaction between DNA-PKcs and PD-L1, and knockdown of DNA-PKcs further reduces the expression of PD-L1. This data provides the first evidence that EPA suppresses the DNA-PKcs/AKT/NRF2/GPX4 pathway to enhance ferroptosis, and inhibits IL-6/STAT3 and DNA-PKcs to decrease PD-L1 expression, thereby sensitizing osteosarcoma to DDP. The combination of EPA and DDP presents an encouraging and promising anti-tumor strategy.