Evaluation of riboflavin concentrations and light intensities on bacteria reduction in platelets using visible light.

Bacterial contamination in platelets has been a major concern over the years. In this study, we showed that treatment with 420 nm visible light with various concentrations of riboflavin in platelets reduced E. coli and S. aureus by 0-1.56 and 0.3-2.02 logs (50 mW/cm2), 2.24-4.77 and 0.73-3.26 logs (75 mW/cm2), and ≥ 5.14 and ≥ 5.27 logs (100 mW/cm2). Treatment with high-intensity light (100 mW/cm2) and high concentrations of riboflavin (400 µM and 500 µM) effectively reduced both bacteria in platelets by over 4 logs. The study also found a positive correlation between bacterial reduction and light intensity, as well as riboflavin concentration in a dose-dependent manner. These results demonstrate the potential of using riboflavin and visible light to reduce the risk of bacterial contamination in platelets, and support the need for further exploration of pathogen reduction using 420 nm visible light and riboflavin.

Psychological resilience mediates sense of professional mission and career success in Chinese intensive care unit nurses: a cross-sectional study.

BACKGROUND: The nursing industry's stability and progress are adversely affected by the high attrition rate and shortage of nurses; therefore, it is critical to investigate the variables that influence the professional stability of nurses. The sense of professional mission and career success have positive significance for reducing nurses' job burnout. The purpose of this study is to explore the potential mediating role of psychological resilience in this relationship. METHODS: Self-reported questionnaires were utilized by 335 intensive care unit (ICU) nurses to assess their sense of professional mission, psychological resilience, and career success in this cross-sectional study. A structural equation model was developed to validate the relationship between the variables. RESULTS: There is a correlation among sense of professional mission, psychological resilience and career success. Significant mediating effect of psychological resilience exists between sense of professional mission and career success. CONCLUSIONS: In this study, psychological resilience plays an intermediary role between sense of professional mission and career success, which provides support for further understanding the mechanism between sense of professional mission and career success and bolstering the case for devising comprehensive intervention strategies for psychological resilience. Nursing managers should focus on nurses' sense of professional mission and psychological resilience, and implement strategies to enhance nurses' psychological resilience in order to boost their career success.

Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Ultrasound-Based Deep Learning Radiomics Nomogram for Tumor and Axillary Lymph Node Status Prediction After Neoadjuvant Chemotherapy.

RATIONALE AND OBJECTIVES: This study aims to explore the feasibility of the deep learning radiomics nomogram (DLRN) for predicting tumor status and axillary lymph node metastasis (ALNM) after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Additionally, we employ a Cox regression model for survival analysis to validate the effectiveness of the fusion algorithm. MATERIALS AND METHODS: A total of 243 patients who underwent NAC were retrospectively included between October 2014 and July 2022. The DLRN integrated clinical characteristics as well as radiomics and deep transfer learning features extracted from ultrasound (US) images. The diagnostic performance of DLRN was evaluated by constructing ROC curves, and the clinical usefulness of models was assessed using decision curve analysis (DCA). A survival model was developed to validate the effectiveness of the fusion algorithm. RESULTS: In the training cohort, the DLRN yielded area under the receiver operating characteristic curve values of 0.984 and 0.985 for the tumor and LNM, while 0.892 and 0.870, respectively, in the test cohort. The consistency indices (C-index) of the nomogram were 0.761 and 0.731, respectively, in the training and test cohorts. The Kaplan-Meier survival curves showed that patients in the high-risk group had significantly poorer overall survival than patients in the low-risk group (P < 0.05). CONCLUSION: The US-based DLRN model could hold promise as clinical guidance for predicting the status of tumors and LNM after NAC in patients with breast cancer. This fusion model can also predict the prognosis of patients, which could help clinicians make better clinical decisions.

Vitamin B-6 Prevents Heart Failure with Preserved Ejection Fraction Through Downstream of Kinase 3 in a Mouse Model.

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation. OBJECTIVES: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF. METHODS: HFpEF model was elicited by a combination of high-fat diet and Nω-nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules. RESULTS: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor. CONCLUSIONS: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

Comprehensive Production Index Prediction Using Dual-Scale Deep Learning in Mineral Processing.

In mineral processing, the dynamic nature of industrial data poses challenges for decision-makers in accurately assessing current production statuses. To enhance the decision-making process, it is crucial to predict comprehensive production indices (CPIs), which are influenced by both human operators and industrial processes, and demonstrate a strong dual-scale property. To improve the accuracy of CPIs' prediction, we introduce the high-frequency (HF) unit and low-frequency (LF) unit within our proposed dual-scale deep learning (DL) network. This architecture enables the exploration of nonlinear dynamic mapping in dual-scale industrial data. By integrating the Cloud-Edge collaboration mechanism with DL, our training strategy mitigates the dominance of HF data and guides networks to prioritize different frequency information. Through self-tuning training via Cloud-Edge collaboration, the optimal model structure and parameters on the cloud server are adjusted, with the edge model self-updating accordingly. Validated through online industrial experiments, our method significantly enhances CPIs' prediction accuracy compared to the baseline approaches.

[Analysis of imaging features of rare tumors in nasal cavity and paranasal sinus].

Objective:To explore the imaging features of rare tumors of nasal cavity and sinuses, and to improve the understanding of these diseases, thereby aiding clinical diagnosis and treatment. Methods:The CT and MRI findings of 79 cases of rare neoplasm of nasal cavity and sinuses confirmed by pathology were retrospectively analyzed, and the imaging features were summarized. Results:Among the 79 cases, there were 16 cases of neuroendocrine carcinoma, most showing expansive and infiltrative bone destruction without hyperosteogeny and sclerosis. The sphenoid sinus exhibited a "pigeon" shape. In 28 cases of malignant melanoma, MRI signals were diverse, typical signals were rare, but mixed signals were more common. In 12 cases of rhabdomyosarcoma, MRI enhancement mostly showed "grape-like" enhancement and partial ring enhancement; There were 10 cases of olfactory neuroblastoma, the lesions were consistent with the distribution area of olfactory mucosa, most of them were lobulated, marginal nodules, and "flower ring" enhancement, and 2 cases grew across intracranial and external, with multiple cystic lesions and surrounding flaky edema bands. In 5 cases of solitary fibrous tumor, Benign tumors had regular shape and uniform density, while malignant tumors had irregular shape and uneven density, The enhancement was obviously uneven and showed a "pattern" change. There were 2 cases of sarcomatoid carcinoma, both with lobed appearance, uneven density, lamellar low-density shadow, and osteolytic bone destruction. In 4 cases of schwannoma, the enhancement showed obvious inhomogeneous enhancement. One case showed cystic necrosis, one case showed calcification, and the surrounding structure was compressed without damage. There was 1 case of neurofibroma, with many cystic components, low signal separation and compartmentalized enhancement. One case of paraganglioma showed moderate enhancement in the arterial phase and progressive enhancement in the venous phase, accompanied by significant swelling bone destruction. Conclusion:Rare tumors of nasal cavity and paranasal sinuses have distinctive imaging features. CT and MRI can effectively show the extent of the lesions and the degree of infiltration into adjacent tissues and organs, which is helpful for early clinical diagnosis and staging. However, definitive diagnosis still depends on pathology and immunohistochemistry.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

Widespread phthalate esters and monoesters in the aquatic environment: Distribution, bioconcentration, and ecological risks.

Field research on phthalate monoesters (MPEs) and their relationships with phthalate esters (PAEs) is limited, especially in wild fishes. Here, PAEs and MPEs were measured in surface water, sediment, and wild fish collected from a representative river basin with high economic development. Several metabolites of emerging plasticizers, such as mono(3,5,5-trimethyl-1-hexyl) phthalate and mono(6-oxo-2-propylheptyl) phthalate, have already existed in fish with high detection frequencies (95 % and 100 %). Monobutyl phthalate and mono(2-ethylhexyl) phthalate were the predominant MPEs in fish and natural environment (surface water and sediment), while bis(2-ethylhexyl) phthalate was the most abundant PAEs in all matrices. The total concentrations (median) of 9 PAEs and 16 MPEs were 5980 and 266 ng/L in water, 231 and 10.6 ng/g (dw) in sediment, and 209 and 32.5 ng/g (ww) in fish, respectively. The occurrence of MPEs was highly related to their parent PAEs, with similar spatial distribution characteristics in the aquatic environments. Moreover, municipal wastewater discharge was recognized as the main source of MPEs in the research area. Fish species can accumulate targeted chemicals, and it seems more MPEs were from the PAE degradation in fish other than the direct uptake of MPEs in water. Parent PAEs showed higher ecological risk than their corresponding metabolites.

A new canthinone glycoside isolated from the root barks of Ailanthus altissima with NO inhibitory activity.

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

Natural Protein Photon Upconversion Supramolecular Assemblies for Background-Free Biosensing.

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.

Multifunctional type lll recombinant human collagen incorporated sodium alginate hydrogel with sustained release of extra cellular vehicles for wound healing multimodal therapy in diabetic mice.

The effective promotion of wound healing poses a substantial challenge for clinical treatment. Despite evidence supporting the role of extracellular vesicles (EVs) in this process, their therapeutic potential is currently restrict by challenges in targeting and maintaining them. The manufacturing process for rhCol III, or recombinant human collagen III, is stable, and the rejection rate is low. We used a cross-linking method to prepare a rhCol III incorporated sodium alginate (SA) hydrogel, which enabled to accomplish an EV sustained release that was site-specific. Cell viability through MTT assay, proliferation and ROS generation were performed with MC3T3-E1cell lines. In addition, diabetic wounds are characterised by an environment of hyper-inflammation and elevated oxidative stress. The rhCol III/SA-EVs hydrogel, which is a delivery vehicle with anti-inflammatory and antioxidant characteristics, promotes wound healing in this setting. The In vivo effectiveness of the created wound dressing on a diabetic wound model was examined in this study. After 21 days of treatment, the wound dressing significantly (p < 0.05) expedited wound healing compared to the control group, and wound closure was approximately 95% without any negative systemic reactions.

Candidatus Liberibacter asiaticus influences the emergence of the Asian citrus psyllid Diaphorina citri by regulating key cuticular proteins.

The Asian citrus psyllid, Diaphorina citri, is the primary vector of the HLB pathogen, Candidatus Liberibacter asiaticus (CLas). The acquisition of CLas shortens the developmental period of nymphs, accelerating the emergence into adulthood and thereby facilitating the spread of CLas. Cuticular proteins (CPs) are involved in insect emergence. In this study, we investigated the molecular mechanisms underlying CLas-promoted emergence in D. citri via CP mediation. Here, a total of 159 CP genes were first identified in the D. citri genome. Chromosomal location analysis revealed an uneven distribution of these CP genes across the 13 D. citri chromosomes. Proteomic analysis identified 54 differentially expressed CPs during D. citri emergence, with 14 CPs exhibiting significant differential expression after CLas acquisition. Five key genes, Dc18aa-1, Dc18aa-2, DcCPR-24, DcCPR-38 and DcCPR-58, were screened from the proteome and CLas acquisition. The silencing of these 5 genes through a modified feeding method significantly reduced the emergence rate and caused various abnormal phenotypes, indicating the crucial role that these genes play in D. citri emergence. This study provides a comprehensive overview of the role of CPs in D. citri and reveals that CLas can influence the emergence process of D. citri by regulating the expression of CPs. These key CPs may serve as potential targets for future research on controlling huanglongbing (HLB) transmission.

Dual Nickel/Photoredox-Catalyzed Arylsulfonylation of Allenes.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway.

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.

The intramolecular self-assembly of bidesmosidic kalopanaxsaponins.

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR (1H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.

Industrial Metaverse-Based Intelligent PID Optimal Tuning System for Complex Industrial Processes.

In this article, the method of dynamic performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes is proposed. This method combines the digital twin model of the PID control process based on system identification and adaptive deep learning and the PID tuning intelligent algorithm based on reinforcement learning with virtual reality and immersive interaction of industrial metaverse. An industrial metaverse-based intelligent PID tuning system is proposed by combining the above method with the end-edge-cloud collaboration technology of Industrial Internet. The challenging problem that the actual operating PID control system in complex industrial processes cannot be optimized online is solved. Using the energy-intensive equipment, the fused magnesium furnace, as an industrial object, we conducted comparative simulation experiments between the proposed control method and several advanced control methods, as well as industrial experiments for the proposed intelligent system. Simulation experiments demonstrate the effectiveness of the proposed control method. The industrial experimental results indicate that the performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes can be realized, which achieves excellent control effects.

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

circ_WASF2 regulates ferroptosis by miR-634/ GPX4 signaling in pancreatic cancer.

PURPOSE: Pancreatic cancer (PC) is one of the most lethal malignant gastrointestinal tumors (GI) characterized by a poor prognosis. Ferroptosis is an emerging programmed cell death that plays an essential role in the progression of various cancers. Ferroptosis is driven by iron-dependent phospholipid peroxidation and is regulated by mitochondrial activity, lipid peroxidation, and reactive oxygen species (ROS). The function and mechanism of ferroptosis in PC need more research. METHODS: The levels of circRNAs, miRNAs, and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used for protein detection. CCK8 assays were used to detect cell proliferation. Cell death, lipid peroxidation, ROS, and Fe2+ were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interaction between circRNAs, miRNAs, and mRNAs. RESULTS: In this research, we found that circular RNA hsa_circ_0000003(circ_WASF2) was upregulated in pancreatic cancer cells. The silence of circ_WASF2 inhibited cancer proliferation and increased cell death by increasing ferroptosis accompanied by up-regulation of lipid peroxidation, ROS, and Fe2+. Further studies showed that circ_WASF2 could attenuate ferroptosis by targeting miR-634 and the downstream glutathione peroxidase 4 (GPX4). GPX4 has been well-reported as a central factor in ferroptosis. Our research revealed a new pathway for regulating ferroptosis in PC. CONCLUSION: In summary, we have determined that circ_WASF2/miR-634/GPX4 contributed to ferroptosis-induced cell death, and provided a possible therapeutic target in PC.