Reducing Water Absorption and Improving Flexural Strength of Aluminosilicate Ceramics by MnO2 Doping.

As key performance indicators, the water absorption and mechanical strength of ceramics are highly associated with sintering temperature. Lower sintering temperatures, although favorable for energy saving in ceramics production, normally render the densification degree and water absorption of as-prepared ceramics to largely decline and increase, respectively. In the present work, 0.5 wt.% MnO2, serving as an additive, was mixed with aluminosilicate ceramics using mechanical stirring at room temperature, achieving a flexural strength of 58.36 MPa and water absorption of 0.05% and lowering the sintering temperature by 50 °C concurrently. On the basis of the results of TG-DSC, XRD, MIP, and XPS, etc., we speculate that the MnO2 additive promoted the elimination of water vapor in the ceramic bodies, effectively suppressing the generation of pores in the sintering process and facilitating the densification of ceramics at a lower temperature. This is probably because the MnO2 transformed into a liquid phase in the sintering process flows into the gap between grains, which removed the gas inside pores and filled the pores, suppressing the generation of pores and the abnormal growth of grains. This study demonstrated a facile and economical method to reduce the porosity and enhance the densification degree in the practical production of aluminosilicate ceramics.

Neonicotinoid insecticides in plant-derived Foodstuffs: A review of separation and determination methods based on liquid chromatography.

Neonicotinoids (NEOs) are the most widely used insecticides globally. They can contaminate or migrate into foodstuffs and exert severe neonic toxicity on humans. Therefore, lots of feasible analytical methods were developed to assure food safety. Nevertheless, there is a lack of evaluation that the impacts of food attributes on the accurate determination of NEOs. This review aims to provide a comprehensive overview of sample preparation methods regarding 6 categories of plant-derived foodstuffs. Currently, QuEChERS as the common strategy can effectively extract NEOs from plant-derived foodstuffs. Various enrichment technologies were developed for trace levels of NEOs in processed foodstuffs, and multifarious novel sorbents provided more possibility for removing complex matrices to lower matrix effects. Additionally, detection methods based on liquid chromatography were summarized and discussed in this review. Finally, some limitations were summarized and new directions were proposed for better advancement.

Achieving One Part Per Billion Hydrogen Sulfide (H2S) Level Detection through Optimizing Composition and Crystallinity of Gold-Decorated Tungsten Trioxide (Au-WO3) Nanofibers.

As a common environmental pollutant and an important breath biomarker for several diseases, it is essential to develop a hydrogen sulfide gas sensor with a low-ppb level detection limit to prevent harmful gas exposure and allow early diagnoses of diseases in low-resource settings. Gold doped/decorated tungsten trioxide (Au-WO3) nanofibers with various compositions and crystallinities were synthesized to optimize H2S-sensing performance. Systematically experimental results demonstrated the ability to detect 1 ppb H2S with a response value (Rair/Rgas) of 2.01 using a 5 at % Au-WO3 nanofibers with average grain sizes of around 15 nm. Additionally, energy barrier difference of sensing materials in air and nitrogen (ΔEb) and power law exponent (n) were determined to be 0.36 eV and 0.7, respectively, at 450 °C indicating that O- is predominately ionic oxygen species and adsorption of O- significantly altered the Schottky barrier between the grain. Such quantitative analysis provides a comprehensive understanding of H2S detection mechanism.

Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.

Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies. ClinicalTrials.gov registration: ChiCTR2100045739 .

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Association between the first 24 hours PaCO2 and all-cause mortality of patients suffering from sepsis-associated encephalopathy after ICU admission: A retrospective study.

OBJECTIVE: The relationship between the levels of the first 24-h PaCO2 and the prognosis of sepsis-associated encephalopathy (SAE) remains unclear, and the first 24-h optimal target for PaCO2 is currently inconclusive. This study was performed to investigate the correlation between PaCO2 and all-cause mortality for SAE patients, establish a reference range of the initial 24-hour PaCO2 for clinicians in critical care, and explain the possible pathophysiological mechanisms of abnormal PaCO2 levels as a higher mortality risk factor for SAE. METHODS: The baseline information and clinical data of patients were extracted from the fourth edition Medical Information Mart for Intensive Care database (MIMIC-IV 2.0). Multivariate logistic regressions were performed to assess the relationship between PaCO2 and all-cause mortality of SAE. Additionally, restricted cubic splines, Kaplan-Meier Survival analyses, propensity score matching (PSM) analyses, and subgroup analyses were conducted. RESULTS: A total of 5471 patients were included in our cohort. In the original and matched cohort, multivariate logistic regression analysis showed that normocapnia and mild hypercapnia may be associated with a more favorable prognosis of SAE patients, and survival analysis supported the findings. In addition, a U-shaped association emerged when examining the initial 24-hour PaCO2 levels in relation to 30-day, 60-day, and 90-day mortality using restricted cubic splines, with an average cut-off value of 36.3mmHg (P for nonlinearity<0.05). Below the cut-off value, higher PaCO2 was associated with lower all-cause mortality, while above the cut-off value, higher PaCO2 was associated with higher all-cause mortality. Subsequent subgroup analyses revealed similar results for the subcohort of GCS≤8 compared to the original cohort. Additionally, when examining the subcohort of GCS>8, a L-shaped relationship between PaCO2 and the three clinical endpoints emerged, in contrast to the previously observed U-shaped pattern. The findings from the subcohort of GCS>8 suggested that patients experiencing hypocapnia had a more unfavorable prognosis, which aligns with the results obtained from corresponding multivariate logistic regression analyses. CONCLUSION: The retrospective study revealed the association between the first 24-h PaCO2 and all-cause mortality risk (30-day, 60-day, and 90-day) for patients with SAE in ICU. The range (35mmHg-50mmHg) of PaCO2 may be the optimal target for patients with SAE in clinical practice.

Platelet mitochondria, a potent immune mediator in neurological diseases.

Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute neurotraumatic insult, and cerebral ischemic/hemorrhagic diseases. Platelets play a fundamental role in normal hemostasis and thrombosis. Beyond those normal functions, platelets are hyperactivated and contribute crucially to inflammation and immune responses in the central nervous system (CNS). Mitochondria are pivotal organelles in platelets and are responsible for generating most of the ATP that is used for platelet activation and aggregation (clumping). Notably, platelet mitochondria show marked morphological and functional alterations under heightened inflammatory/oxidative stimulation. Mitochondrial dysfunction not only leads to platelet damage and apoptosis but also further aggravates immune responses. Improving mitochondrial function is hopefully an effective strategy for treating neurological diseases. In this review, the authors discuss the immunomodulatory roles of platelet-derived mitochondria (PLT-mitos) in neurological diseases and summarize the neuroprotective effects of platelet mitochondria transplantation.

Platelet morphology, ultrastructure and function changes in acute ischemic stroke patients based on structured illumination microscopy.

Acute ischemic stroke (AIS) is the second leading cause of death worldwide. This study aims at assessing platelet morphology, ultrastructure and function changes of platelets in acute ischemic stroke (AIS) patients by the technique of Structured Illumination Microscopy (SIM). This assay collected platelet-rich plasma (PRP) from 11 AIS patients and 12 healthy controls. Each PRP sample was divided into 7 groups:1) rest group; 2) Thrombin-treated 5 min group; 3) Thrombin plus 2MeSAMP-treated 5 min group; 4) Thrombin plus Aspirin-treated 5 min group; 5) Thrombin-treated 1 h group; 6) Thrombin plus 2MeSAMP-treated 1 h group; 7) Thrombin plus Aspirin-treated 1 h group. SIM was applied to observe dense granules and α-granules morphology changes of platelet in AIS patients. FIJI was used to quantify the image data. We finally observed 1448 images of platelets within the 7 groups. In rest group, 7162 platelets were calculated platelet diameter, CD63 dots, average CD63-positive dots area, CD63-positive area per platelet, CD63-positive area Fov, VWF dots, average VWF-positive dots area, VWF-positive area per platelet and VWF-positive area Fov. ELISA was used to detect release of platelet factor 4 (PF4) of α-granules. The results showed that AIS patients had lower number and smaller area of platelet granules. Platelet α-granules of AIS patients concentrated to parenchymal-like fluorescent blocks in Thrombin-treated 1 h group. Antiplatelet drug treatment could reverse the concentration of platelets α-granules, and 2MeSAMP was more powerful than Aspirin in vitro. This study complemented detail information of platelet ultrastructure of AIS patients, provided a new perspective on the pathogenesis of AIS and the mechanism of antiplatelet drugs based on SIM and provided a reference for future related studies. SIM-based analysis of platelet ultrastructure may be useful for detecting antiplatelet drugs and AIS in the future.

Simultaneous Determination of Neonicotinoid and Carbamate Pesticides in Freeze-Dried Cabbage by Modified QuEChERS and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Dehydrated vegetables are popular in instant foods, but few reports have focused on their pesticide residues. This research developed and validated a modified QuEChERS method combined with ultra-performance liquid chromatography-tandem mass spectrometry to determine 19 kinds of neonicotinoid and carbamate pesticides in freeze-dried cabbage. Herein, acetonitrile/water (v/v = 2:1) was selected in the extraction step. Meanwhile, 4 g anhydrous magnesium sulfate and 1 g sodium chloride were applied to the partitioning step. Dispersive solid-phase extraction sorbents were selected, and liquid chromatography conditions were further optimized for dealing with the matrix effect. The limits of quantification ranged from 1.0 to 10.0 µg/kg. The validation results were acceptable, with average recoveries of 78.7-114.0% and relative standard deviations below 14.2%. The method recoveries were closely related to the volume proportion of water in the extractant. Finally, the developed method was applied to real freeze-dried cabbages and four pesticides (propamocarb, imidacloprid, acetamiprid, and thiacloprid) were detected in six samples.

Chlorantraniliprole in foods: Determination, dissipation and decontamination.

Chlorantraniliprole (CAP) is the first commercially available anthranilic diamide insecticide that targets ryanodine receptors. However, excessive use of CAP can lead to persistent contamination on treated foods and adverse effects on human wellness. The current review focuses on CAP residue analysis in foods by using chromatographic techniques. QuEChERS (quick, easy, cheap, effective, rugged and safe) is the most widely used sample preparation strategy and liquid chromatography tandem mass spectrometry is the predominant analytical method for various food matrices including vegetable, fruit, grain, fish and so on. Moreover, this review summarizes the dissipation pattern of CAP on foods and found it usually dissipates fast on plant in open-field environment. For decontamination, common culinary cleaning methods could effectively remove CAP from vegetables. Finally, some new directions are proposed for better advancement.

Nitrous Oxide Is No Laughing Matter: A Historical Review of Nitrous Oxide Gas-Sensing Capabilities Highlighting the Need for Further Exploration.

Nitrous oxide (N2O), also known as laughing gas, is arguably one of the most detrimental greenhouse gases while concurrently being overlooked by the public. Specifically, N2O is ∼300 times more damaging than its better-known counterpart carbon dioxide (CO2) and has a longer-lived lifetime in the atmosphere than CO2. There exist both natural and anthropogenic sources of N2O, and thus, for a better understanding of sources, capture, and decomposition, it is pivotal to identify N2O within the nitrogen biosphere. This review covers the past and current low-cost N2O gas-sensing technologies, focusing specifically on low-cost metal oxide semiconductors (MOSs), chemiresistive and electrochemical sensors that can provide spatial and temporal monitoring of N2O emissions from various sources. Additionally, compositional modifications to MOsS using metal-organic frameworks (MOFs) are discussed, potentially facilitating new awareness and efforts for increased sensing performance and functionality in N2O detection.

Genetic deconvolution of fetal and maternal cell-free DNA in maternal plasma enables next-generation non-invasive prenatal screening.

Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

Impurity Profiling of Dinotefuran by High Resolution Mass Spectrometry and SIRIUS Tool.

Dinotefuran (DNT) is a neonicotinoid insecticide widely used in pest control. Identification of structurally related impurities is indispensable during material purification and pesticide registration and certified reference material development, and therefore needs to be carefully characterized. In this study, a combined strategy with liquid chromatography high-resolution mass spectrometry and SIRIUS has been developed to elucidate impurities from DNT material. MS and MS/MS spectra were used to score the impurity candidates by isotope score and fragment tree in the computer assisted tool, SIRIUS. DNT, the main component, worked as an anchor for formula identification and impurity structure elucidation. With this strategy, two by-product impurities and one stereoisomer were identified. Their fragmentation pathways were concluded, and the mechanism for impurity formation was also proposed. This result showed a successful application for combined human intelligence and machine learning, in the identification of pesticide impurities.

Impurity identification in thiamethoxam by high resolution mass spectrometry and computer assisted elucidation.

Thiamethoxam (TMX) is a widely used neonicotinoid insecticide in pest control. Identification of structurally related impurities is very important during certified reference material development and pesticide registration, thus it needs to be carefully characterized. In this study, a combined strategy with liquid chromatography-high resolution mass spectrometry and computer assisted elucidation (SIRIUS) has been developed for the impurity elucidation in TMX material. MS and MS/MS spectra were used to score the impurity candidates by isotope score and fragment tree in SIRIUS. TMX, the main component, worked as an anchor for formula identification and structure elucidation of impurity. With this strategy, four impurities were identified, including two byproducts (TMX-OCH3 and TMX-Cl) and two metabolites (clothianidin and TMX-urea). Their fragmentation pathways were concluded, and mechanism of impurity formation was also proposed. This result showed successful application of combining human intelligence with machine learning in impurity identification from chemicals.

Maltose-functional metal-organic framework assisted laser desorption/ionization mass spectrometry for small biomolecule determination.

A series of functional metal-organic frameworks (MOFs) were facilely prepared through an one-pot procedure or post-synthetic modification strategy and used as matrices in laser desorption ionization mass spectrometry (LDI-MS). Compared with traditional organic matrices and other MOFs, maltose-functional MOF MIL-101-maltose demonstrated ultrahigh ionization efficiency, free matrix background, uniform crystallization, and good dispersibility. A simple, general, and efficient LDI-MS platform was developed for rapid detection of various small biomolecules using MIL-101-maltose as matrix, providing several advantages including low sample consumption of 500 nL, short analysis time of few seconds, strong salt tolerance (500 mM NaCl), and satisfactory reproducibility. The MIL-101-maltose matrix was used for serum glucose determination and successfully distinguished the diabetic patients from the healthy controls. This work provides a generic LDI-MS platform for fast determination of small biomolecules with high potential in clinical diagnosis and disease monitoring.

Determination of eight neonicotinoid insecticides in Chinese cabbage using a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry.

A modified QuEChERS method was developed and combined with ultra performance liquid chromatography-tandem mass spectrometry to analyze eight neonicotinoid insecticides in Chinese cabbage. Herein, acetonitrile served as extraction solvent. Anhydrous sodium sulfate replaced the traditional anhydrous magnesium sulfate in the phase partition process to eliminate the influence of salt caking and heat release. Primary secondary amine and graphitized carbon black were selected as dispersive-solid phase extraction sorbents according to the clean-up efficiency evaluated by post-column infusion. The method showed good sensitivity with the limits of quantification below 1.0 µg/kg for eight analytes. The average recoveries ranged from 79.0% to 108.4% for three fortification levels, and the matrix effect could be ignored. For the tested samples, six neonicotinoids were detected, while cycloxaprid and imidaclothiz were not. The developed analytical method provided a powerful tool for monitoring neonicotinoid insecticides residues in Chinese cabbage.

Extracellular vesicle-derived long non-coding RNA as circulating biomarkers for endometriosis.

RESEARCH QUESTION: Could extracellular vesicle-derived long non-coding RNA (lncRNA) serve as promising circulating biomarkers for endometriosis? DESIGN: To obtain novel diagnostic markers, 85 patients with endometriosis were enrolled as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify extracellular vesicle-derived lncRNA that were differentially expressed between women with endometriosis (n = 5) and unaffected participants (n = 6). Messenger RNA and lncRNA sequences of the plasma extracellular vesicles were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. lncRNA expression levels were further validated using quantitative reverse transcriptase polymerase chain reaction. Moreover, receiver operating characteristic curve analysis was performed to determine the diagnostic value of candidate lncRNA. Clinical features were correlated to the expression levels of candidate lncRNA. RESULTS: It was found that 210 lncRNA were significantly dysregulated; among these, expression of LINC01569, RP3-399L15.2, FAM138B and CH507-513H4.6 was significantly decreased, whereas expression of RP11-326N17.2, KLHL7-AS1 and MIR548XHG was increased, in the plasma of patients with endometriosis. Combined expression level of RP3-399L15.2 and CH507-513H4.6 was used to distinguish patients with endometriosis from control participants; the results revealed a sensitivity of 80.00% and specificity of 85.45% at the cut-off point, and an area under the ROC curve of 0.9045. The findings demonstrated the potential of these two lncRNA as diagnostic biomarkers for endometriosis. Moreover, CH507-513H4.6 alone may be useful in detecting early-stage endometriosis lesions. CONCLUSIONS: The combination of RP3-399L15.2 and CH507-513H4.6 may be a potential candidate for endometriosis biomarkers.

Piezo-photocatalytic flexible PAN/TiO2 composite nanofibers for environmental remediation.

Mechanical vibrations and solar energy are ubiquitous in the environment. Hereon, we report the synergic enhancement of the oxidation by simultaneously harvesting solar and mechanical vibrations through flexible piezo and photocatalytic composite nanofiber mats. Surface enriched titanium dioxide nanoparticles incorporated in polyacrylonitrile (PAN/TiO2) nanofibers were synthesized using a single pot electrospinning process with well-defined fiber diameters with widely tunable loading density. By incorporating photocatalytic TiO2 in flexible piezoelectric PAN nanofiber support, piezoelectric fields generated under the mechanical deformation promote the separation of the photogenerated electrons and holes to accelerate oxidation of pollutants. Our results demonstrated that the catalytic activity of PAN/TiO2 nanofibers in photodegradation of Rhodamine B (RhB) can be greatly enhanced by environmental vibration-induced piezoelectricity of PAN nanofibers, with a maximum enhancement factor of ~2.5. The working mechanism for the enhanced photocatalytic activity of PAN/TiO2 nanofibers by the mechanical vibrations were attributed to the piezoelectric effect of PAN nanofibers, which could efficiently promote the separation of the photogenerated electrons and holes in the TiO2 nanoparticles. We believe the approach to enhancing the catalytic activity of mat can make full use of the polymer properties and natural energy, and it also can be extended to other composite polymer/semiconductor systems.

Development of a Simple, Underivatized Method for Rapid Determination of Free Amino Acids in Honey Using Dilute-and-Shoot Strategy and Liquid Chromatography-Tandem Mass Spectrometry.

A simple, fast and reliable analytical method was developed for 20 free amino acids (FAAs) determination in honey samples through a dilute-and-shoot strategy and hydrophilic interaction liquid chromatography tandem mass spectrometry. Compared with previous reports, direct dilution by water has significantly reduced the matrix effect and facilitated full extraction of FAAs. Further, a 5 min determination method was established with an acetonitrile-water mobile phase system with 0.1% formic acid addition. The established method was validated and demonstrated several advantages including short detection time, wide linear range over 3-4 orders of magnitude, high sensitivity down to 0.1 ng/mL and negligible matrix effect. Twenty FAAs were determined in 10 honey samples from different botanical origins by this method, and 19 FAAs were found. This general applicable method was also promising for fast determination of FAAs in other practical samples.

Endometrial stromal cell ferroptosis promotes angiogenesis in endometriosis.

Endometriosis, a chronic disorder characterised by the presence of endometrial-like tissue outside the uterus, is associated with iron overload and oxidative stress in the lesion. Although it is well established that iron overload can trigger ferroptosis, the results of previous studies on ferroptosis resistance and ferroptosis in endometriotic lesions are paradoxical. Here, we found that some stromal cells of the cyst walls that were in contact with the cyst fluid underwent ferroptosis. Surprisingly, endometrial stromal cell ferroptosis triggered the production of angiogenic, inflammatory and growth cytokines. In particular, angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8), promoted human umbilical vein endothelial cell (HUVEC) vascular formation in vitro. Moreover, we found that inhibition of p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6 (p38 MAPK/STAT6) signalling represses VEGFA and IL8 expression when endometrial stromal cells undergo ferroptosis. Notably, VEGFA and IL8 showed localised expression and were significantly upregulated in ectopic lesions compared to control and eutopic endometrium samples from patients with endometriosis. Thus, our study reveals that endometrial stromal cell ferroptosis in the ovarian endometrioma may trigger cytokine secretion and promote angiogenesis of adjacent lesions via paracrine actions to drive the development of endometriosis, providing a rationale for translation into clinical practice and developing drugs for endometriosis.