Multifunctional mesoporous nanoselenium delivery of metformin breaks the vicious cycle of neuroinflammation and ROS, promotes microglia regulation and alleviates Alzheimer's disease.

Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aß protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aß deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.

Environmentally relevant level of PFDA exacerbates intestinal inflammation by activating the cGAS/STING/NF-κB signaling pathway.

As a constituent of the Per- and Polyfluoroalkyl Substances (PFAS) family, perfluorodecanoic acid (PFDA) is ubiquitous in the environment and enters the human body through environmental exposure, the food chain, and other pathways, resulting in various toxic effects. Previous population-based studies have suggested a correlation between PFDA exposure and inflammation. However, the evidence is still limited, and the potential mechanisms underlying this correlation remain to be further elucidated. In our study, we observed that exposure to internal doses of PFDA significantly promoted macrophage inflammation through in vitro assays. Utilizing RNA-seq screening and molecular experiments, we identified that environmentally relevant concentration of PFDA promote inflammation mainly by activating non-canonical cGAS/STING/NF-κB pathways in vitro. Finally, we confirmed in the typical mouse inflammatory bowel disease (IBD) model that PFDA could exacerbate intestinal inflammation in a cGAS dependent manner. In conclusion, our research firstly demonstrated that even at environmentally relevant concentrations, PFDA could promote the progression of intestinal inflammation primarily through the cGAS/STING/NF-κB pathway, revealing the potential risk associated with PFDA exposure and providing theoretical evidence for its management.

Structurally diverse triterpenoids with antibacterial activities from Euphorbia humifusa.

An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A-N (1-7 and 9-15), as well as four known analogues (8 and 16-18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7 â†’ 8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,ß-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12.5, 25, and 25 µg/mL, comparable to the positive controls. Upon exposure to 1 and 2 MIC of 1, B.cereus underwent drastic morphological changes, resulting in complete disruption of the cells. Meanwhile, compound 1 also exhibited remarkable antibiofilm activity against B.cereus at 1 MIC and 2 MIC.

Mitochondria-targeting Cu2-xSe-TPP with dual enzyme activity alleviates Alzheimer's disease by modulating oxidative stress.

Mitochondrial dysfunction in microglia has been implicated as a key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). Abnormal production of reactive oxygen species (ROS) and neuroinflammation caused by mitochondrial oxidative stress are important factors leading to neuronal death in AD. Herein, a "dual brake" strategy to synergistically halt mitochondrial dysfunction and neuroinflammation targeting mitochondria in microglia is proposed. To achieve this goal, (3-carboxypropyl) triphenyl-phosphonium bromide (TPP)-modified Cu2-xSe nanozymes (Cu2-xSe-TPP NPs) with dual enzyme-like activities was designed. Cu2-xSe-TPP NPs with superoxide dismutase-mimetic (SOD) and catalase-mimetic (CAT) activities can effectively scavenge ROS in the mitochondria of microglia and relieve mitochondrial oxidative stress. In vivo studies demonstrated that Cu2-xSe-TPP NPs can alleviate oxidative stress and promote neuroprotection in the hippocampus of AD model mice. In addition, Cu2-xSe-TPP NPs can regulate the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, promote Aß phagocytosis and reshape the AD inflammatory microenvironment, thus effectively attenuating AD neuropathology and rescuing cognitive deficits in AD model mice. Taken together, this strategy preventing mitochondrial damage and remodeling the inflammatory microenvironment will provide a new perspective for AD therapy.

Environmentally relevant concentrations of perfluorobutane sulfonate impair locomotion behaviors and healthspan by downregulating mitophagy in C. elegans.

Perfluorobutane sulfonate (PFBS), a chemical compound within the group of per- and polyfluoroalkyl substances (PFAS), has been utilized as an alternative to perfluorooctane sulfonate (PFOS) recently. Previous research has indicated that PFBS might be linked to a range of health concerns. However, the potential impacts of environmentally relevant concentrations of PFBS (25 nM) on aging as well as the underlying mechanisms remained largely unexplored. In this study, we investigated the impact of PFBS exposure on aging and the associated mechanisms in Caenorhabditis elegans. Our findings indicated that exposure to PFBS impaired healthspan of C. elegans. Through bioinformatic screening analyses, we identified that the dysfunctions of pink-1 mediated mitophagy might play a critical role in PFBS induced aging. The results furtherly revealed that PFBS exposure led to elevated levels of reactive oxygen species (ROS) and mitophagy impairment through downregulating pink-1/pdr-1 pathway. Furthermore, the mitophagy agonist Urolithin A (UA) effectively reversed PFBS-induced mitophagy dysfunction and enhanced healthspan in C. elegans. Taken together, our study suggested that exposure to environmentally relevant concentrations of PFBS could accelerate aging by downregulating the pink-1 mediated mitophagy. Promoting mitophagy within cells could be a promising therapeutic strategy for delaying PFBS-induced aging.

CRISPR/Cas9-Mediated Resistance to Wheat Dwarf Virus in Hexaploid Wheat (Triticum aestivum L.).

Wheat dwarf virus (WDV, genus Mastrevirus, family Geminiviridae) is one of the causal agents of wheat viral disease, which severely impacts wheat production in most wheat-growing regions in the world. Currently, there is little information about natural resistance against WDV in common wheat germplasms. CRISPR/Cas9 technology is being utilized to manufacture transgenic plants resistant to different diseases. In the present study, we used the CRISPR/Cas9 system targeting overlapping regions of coat protein (CP) and movement protein (MP) (referred to as CP/MP) or large intergenic region (LIR) in the wheat variety 'Fielder' to develop resistance against WDV. WDV-inoculated T1 progenies expressing Cas9 and sgRNA for CP/MP and LIR showed complete resistance against WDV and no accumulation of viral DNA compared with control plants. Mutation analysis revealed that the CP/MP and LIR targeting sites have small indels in the corresponding Cas9-positive plants. Additionally, virus inhibition and indel mutations occurred in T2 homozygous lines. Together, our work gives efficient results of the engineering of CRISPR/Cas9-mediated WDV resistance in common wheat plants, and the specific sgRNAs identified in this study can be extended to utilize the CRISPR/Cas9 system to confer resistance to WDV in other cereal crops such as barley, oats, and rye.

Green fabrication of modified lignin/zeolite/chitosan-based composite membranes for preservation of perishable foods.

Chitosan, as a kind of naturally occurring green and degradable material for the preservation of perishable foods, was investigated in this study with the objective of enhancing its preservation performances. Herein, lignin was modified using the solvent fractionation method (modified lignin, ML, including ML1-ML3), while natural clinoptilolite zeolite was modified using the alkali modification method (modified clinoptilolite zeolite, MCZ, including MCZ1-MCZ5). After optimizing the conditions, it was discovered that incorporating both ML3 and MCZ3 into pure chitosan-based membranes might be conducive to fabricate chitosan-based composite membranes for the preservation of perishable foods. As-prepared composite membranes possessed better visible light transmittance, antioxidant activity, and carbon dioxide/oxygen selectivity, resulting in improved preservation effects on the model perishable foods such as bananas, cherry tomatoes, and cheeses. These findings might indicate promising applications for chitosan-based composite membranes with modified lignin and zeolite in the field of eco-friendly degradable materials for the preservation of perishable foods.

Environmentally relevant concentration PFNA promotes degradation of SMAD7 to drive progression of ovarian cancer via TGF-ß/SMADs signaling pathway.

Perfluorononanoic acid (PFNA), an acknowledged environmental endocrine disruptor, is increasingly utilized as a substitute for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Despite its growing use, limited research has been conducted to investigate its potential impact on tumorigenesis and progression, and the potential molecular mechanisms. Earlier studies linked perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to breast and gynecological cancer progression in humans, lacking a clear understanding of the underlying mechanisms, notably in ovarian cancer. Our investigation into PFNA's effects at environmental concentrations (0.25-2 mM) showed no significant impact on cell proliferation but a notable increase in invasion and migration of ovarian cancer cells. This led to alterations in epithelial-mesenchymal transition (EMT) markers, including Claudin1, Vimentin, and Snail. Notably, PFNA exposure activated the TGF-ß/SMADs signaling pathway. Crucially, SMAD7 degradation through the ubiquitin-proteasome system emerged as PFNA's pivotal molecular target for inducing EMT, corroborated in mouse models. In summary, this study presented evidence that environmentally relevant concentrations of PFNA could induce SMAD7 degradation via the proteasome pathway, subsequently activating the TGF-ß/SMADs signaling pathway, and promoting EMT in ovarian cancer. These results illuminated the association between PFNA exposure and metastasis of ovarian cancer.

Atomic-Layer-Controlled Magnetic Orders in MnBi2Te4-Bi2Te3 Topological Heterostructures.

The natural van der Waals superlattice MnBi2Te4-(Bi2Te3)m provides an optimal platform to combine topology and magnetism in one system with minimal structural disorder. Here, we show that this system can harbor both ferromagnetic (FM) and antiferromagnetic (AFM) orders and that these magnetic orders can be controlled in two different ways by either varying the Mn-Mn distance while keeping the Bi2Te3/MnBi2Te4 ratio constant or vice versa. We achieve this by creating atomically engineered sandwich structures composed of Bi2Te3 and MnBi2Te4 layers. We show that the AFM order is exclusively determined by the Mn-Mn distance, whereas the FM order depends only on the overall Bi2Te3/MnBi2Te4 ratio regardless of the distance between the MnBi2Te4 layers. Our results shed light on the origins of the AFM and FM orders and provide insights into how to manipulate magnetic orders not only for the MnBi2Te4-Bi2Te3 system but also for other magneto-topological materials.

PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/ß-catenin signaling.

Perfluoroundecanoic acid (PFDA) is extensively utilized in the textile and food processing industries and may have a tumor-promoting effect by modulating the tumor microenvironment. Macrophages play crucial roles in tumor microenvironment as key regulators of tumor immunity. However, further investigation is needed to elucidate how PFDA interacts with macrophages and contributes to tumor progression. In this study, we treated the macrophage cell line RAW264.7 with various concentrations of PFDA and found that RAW264.7 transitioned into an M2 tumor-promoting phenotype. Through bioinformatic analysis and subsequent verification of molecular assays, we uncovered that PFDA could activate ß-catenin and enhance its nuclear translocation. Additionally, it was also observed that inhibiting ß-catenin nuclear translocation partly attenuated RAW264.7 M2 polarization induced by PFDA. The conditioned medium derived from PFDA-pretreated RAW264.7 cells significantly promoted the migration and invasion abilities of human ovarian cancer cells. Furthermore, in vivo studies corroborated that PFDA-pretreated RAW264.7 could promote tumor metastasis, which could be mitigated by pretreatment with the ß-catenin inhibitor ICG001. In conclusion, our study demonstrated that PFDA could promote cancer metastasis through regulating macrophage M2 polarization in a Wnt/ß-catenin-dependent manner.

Resilient Growth of a Highly Crystalline Topological Insulator-Superconductor Heterostructure Enabled by an Ex Situ Nitride Film.

Highly crystalline and easily feasible topological insulator-superconductor (TI-SC) heterostructures are crucial for the development of practical topological qubit devices. The optimal superconducting layer for TI-SC heterostructures should be highly resilient against external contamination and structurally compatible with TIs. In this study, we provide a solution to this challenge by showcasing the growth of a highly crystalline TI-SC heterostructure using refractory TiN (111) as the superconducting layer. This approach can eliminate the need for in situ cleavage or growth. More importantly, the TiN surface shows high resilience against contaminations during air exposure, as demonstrated by the successful recyclable growth of Bi2Se3. Our findings indicate that TI-SC heterostructures based on nitride films are compatible with device fabrication techniques, paving the way to the realization of practical topological qubit devices in the future.

Perioperative fluid balance and early acute kidney injury after lung transplantation.

BACKGROUND: Postoperative acute kidney injury (AKI) after lung transplantation (LTx) is an important factor affecting the short-term outcomes. The focus item of transplantation centers is how to improve the incidence of AKI through optimal management during the perioperative period. OBJECTIVE: The purpose of the study is to investigate the influence of perioperative volume in the development of early AKI following LTx. METHOD: The study involved patients who had undergone LTx between October 2018 to December 2021 at China-Japan Friendship Hospital in Beijing. The patients were monitored for AKI occurring within 72 hours after LTx, as well as the renal outcomes within 30 days. The perioperative volumes were compared and analyzed to determine the impact on various clinical outcomes. RESULTS: 248 patients were enrolled in the study ultimately, with almost half of them (49.6 %) experiencing AKI. 48.8 % of AKI patients received continuous renal replacement therapy (CRRT), with 57.7 % recovered by the end of the 30-day follow-up period. A J-shaped relationship was demonstrated between perioperative volume and AKI incidence. Moreover, maintaining a positive fluid balance would increase the 30-day mortality and lead to poor renal outcomes. CONCLUSION: Perioperative volume is an independent risk factor of early AKI after LTx. Positive fluid balance increases the risk of AKI, 30-day mortality, and adverse renal prognosis. The LTx recipients may benefit from a relatively restrict fluid strategy during and after the lung transplantation.

Predictive value of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) for the short-term mortality of older patients with isolated traumatic brain injury: a retrospective cohort study.

OBJECTIVES: This study aimed to evaluate the effectiveness of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) in predicting 24-hour in-hospital mortality among patients aged 65 years and older with isolated traumatic brain injury (TBI). DESIGN: A retrospective, single-centre cohort study. SETTING: This study was conducted at a government-run tertiary comprehensive hospital. PARTICIPANTS: This study included 982 patients aged 65 years or older with isolated TBI, who were admitted to the emergency department between 1 January 2020 and 31 December 2021. INTERVENTIONS: None. PRIMARY OUTCOME: 24-hour in-hospital mortality was the primary outcome. RESULTS: Among the 982 patients, 8.75% died within 24 hours of admission. The non-survivors typically had higher TRIAGES and lower GCS scores. Logistic regression showed significant associations of both TRIAGES and GCS with mortality; the adjusted ORs were 1.98 (95% CI 1.74 to 2.25) for TRIAGES and 0.72 (95% CI 0.68 to 0.77) for GCS. Receiver operating characteristic (ROC) analysis indicated an area under the ROC curve of 0.86 for GCS and 0.88 for TRIAGES, with a significant difference (p=0.012). However, precision-recall curve (PRC) analysis revealed an area under the PRC of 0.38 for GCS and 0.47 for TRIAGES, without a significant difference (p=0.107). CONCLUSIONS: The TRIAGES system is a promising tool for predicting 24-hour in-hospital mortality in older patients with TBI, demonstrating comparable or slightly superior efficacy to the GCS. Further multicentre studies are recommended for validation.

Genomic and biological characteristics of a novel leafhopper-transmitted marafivirus infecting Triticum aestivum.

Here, we report a novel wheat-infecting marafivirus, tentatively named "Triticum aestivum marafivirus" (TaMRV). The full-length genome sequence of TaMRV comprises 6,437 nucleotides, excluding the poly(A) tail. Pairwise sequence comparisons and phylogenetic analysis revealed that TaMRV may represent a novel species within the genus Marafivirus in the family Tymoviridae. We also observed a mass of isometric particles with a diameter of about 30 nm in ultrathin sections of infected wheat leaf tissue. In addition, the leafhopper Psammotettix alienus was identified as a vector for this virus. This is the first report of the occurrence of a wheat-infecting marafivirus.

Recent advances in hypoxia-activated compounds for cancer diagnosis and treatment.

Hypoxia, as a prevalent feature of solid tumors, is correlated with tumorigenesis, proliferation, and invasion, playing an important role in mediating the drug resistance and affecting the cancer treatment outcomes. Due to the distinct oxygen levels between tumor and normal tissues, hypoxia-targeted therapy has attracted significant attention. The hypoxia-activated compounds mainly depend on reducible organic groups including azo, nitro, N-oxides, quinones and azide as well as some redox-active metal complex that are selectively converted into active species by the increased reduction potential under tumor hypoxia. In this review, we briefly summarized our current understanding on hypoxia-activated compounds with a particular highlight on the recently developed prodrugs and fluorescent probes for tumor treatment and diagnosis. We have also discussed the challenges and perspectives of small molecule-based hypoxia-activatable prodrug for future development.

Dual-functionalized two-dimensional metal-organic framework composite with highly hydrophilicity for effective enrichment of glycopeptides.

Protein glycosylation research is currently focused on the development of various functionalized materials that can effectively enrich the levels of glycopeptides in samples. However, most of these materials possess limited glycopeptide-specific recognition sites because of large steric hindrance, unsuitable mass transfer kinetics, and relatively low surface areas. Herein, a highly hydrophilic two-dimensional (2-D) metal-organic framework (MOF) nanosheet modified with glutathione (GSH) and l-cysteine (l-Cys) (denoted as Zr-Fc MOF@Au@GC) has been synthesized for efficient glycopeptide enrichment. Using this composite material, 39 and 44 glycopeptides from horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG) digests were detected, respectively, which represents a higher efficiency for glycopeptide enrichment from model glycoprotein digests than has been previously reported. The material Zr-Fc MOF@Au@GC exhibited ultra-high sensitivity (0.1 fmol/µL), excellent selectivity (weight ratio of HRP tryptic digest to bovine serum albumin (BSA) tryptic digest = 1:2000), good binding capacity (200 mg/g), satisfactory reusability, and long-term storage capacity. In addition, 655 glycopeptides corresponding to 366 glycoproteins were identified from human serum samples. To the best of our knowledge, this is the largest number of glycoproteins detected in human serum samples to date. These results indicated that Zr-Fc MOF@Au@GC has the potential to be used for the enrichment of glycopeptides in biological samples and the analysis of protein glycosylation.

PINK1-PTEN axis promotes metastasis and chemoresistance in ovarian cancer via non-canonical pathway.

BACKGROUND: Ovarian cancer is commonly associated with a poor prognosis due to metastasis and chemoresistance. PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that plays a crucial part in regulating various physiological and pathophysiological processes in cancer cells. METHODS: The ATdb database and "CuratedOvarianData" were used to evaluate the effect of kinases on ovarian cancer survival. The gene expression in ovarian cancer cells was detected by Western blot and quantitative real-time PCR. The effects of gene knockdown or overexpression in vitro were evaluated by wound healing assay, cell transwell assay, immunofluorescence staining, immunohistochemistry, and flow cytometry analysis. Mass spectrometry analysis, protein structure analysis, co-immunoprecipitation assay, nuclear-cytoplasmic separation, and in vitro kinase assay were applied to demonstrate the PINK1-PTEN (phosphatase and tensin homolog) interaction and the effect of this interaction. The metastasis experiments for ovarian cancer xenografts were performed in female BALB/c nude mice. RESULTS: PINK1 was strongly associated with a poor prognosis in ovarian cancer patients and promoted metastasis and chemoresistance in ovarian cancer cells. Although the canonical PINK1/PRKN (parkin RBR E3 ubiquitin protein ligase) pathway showed weak effects in ovarian cancer, PINK1 was identified to interact with PTEN and phosphorylate it at Serine179. Remarkably, the phosphorylation of PTEN resulted in the inactivation of the phosphatase activity, leading to an increase in AKT (AKT serine/threonine kinase) activity. Moreover, PINK1-mediated phosphorylation of PTEN impaired the nuclear import of PTEN, thereby enhancing the cancer cells' ability to resist chemotherapy and metastasize. CONCLUSIONS: PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. PINK1 promotes ovarian cancer metastasis and chemotherapy resistance through the regulation of PTEN. These findings offer new potential therapeutic targets for ovarian cancer management.

Hypobaric hypoxia induces iron mobilization from liver and spleen and increases serum iron via activation of ghrelin/GHSR1a/MAPK signalling pathway in mice.

Hypobaric hypoxia (HH) exposure affects appetite and serum iron levels in both humans and animals. Thus, whether appetite-regulating ghrelin is involved in iron regulation under HH needs to be elucidated. In vivo, C57BL/6J mice were placed in a hypobaric chamber to establish a 6000-m-high altitude exposure animal model. In vitro, mouse primary hepatocytes and peritoneal macrophages were exposed to hypoxia (1% O2) to examine the effects of ghrelin on iron-regulating proteins. HH obviously reduced the body weight of mice and significantly increased the levels of erythrocytes, and also significantly enhanced the levels of serum iron and plasma ghrelin. However, iron content in the liver and spleen was decreased, while ferroportin (Fpn) expression was increased. Moreover, ghrelin significantly induced Fpn and pERK expression in both hepatocytes and macrophages under hypoxia, which were reversed by pretreatment with growth hormone secretagogue receptor 1a (GHSR1a) antagonist or pERK inhibitor. Our findings indicated that HH leads to decreased appetite and insufficient dietary intake, which may negatively regulate the levels of ghrelin. Furthermore, GHSR1a/ERK signalling pathway is further activated to upregulate the expression of Fpn, and then promoting iron mobilization both in the liver/hepatocytes and spleen/macrophages in mice. Thus, these results revealed that ghrelin may be a potential iron regulatory hormone, and raised the possibility of ghrelin as a promising therapeutic target against iron disorders under HH.

Low dose PFDA induces DNA damage and DNA repair inhibition by promoting nuclear cGAS accumulation in ovarian epithelial cells.

Per- and polyfluoroalkyl substances (PFAS), the versatile anthropogenic chemicals, are popular with the markets and manufactured in large quantities yearly. Accumulation of PFAS has various adverse health effects on human. Albeit certain members of PFAS were found to have genotoxicity in previous studies, the mechanisms underlying their effects on DNA damage repair remain unclear. Here, we investigated the effects of Perfluorodecanoic acid (PFDA) on DNA damage and DNA damage repair in ovarian epithelial cells through a series of in vivo and in vitro experiments. At environmentally relevant concentration, we firstly found that PFDA can cause DNA damage in primary mouse ovarian epithelial cells and IOSE-80 cells. Moreover, nuclear cGAS increased in PFDA-treated cells, which leaded to the efficiency of DNA homologous recombination (HR) decreased and DNA double-strand breaks perpetuated. In vivo experiments also verified that PFDA can induce more DNA double-strand breaks lesions and nuclear cGAS in ovarian tissue. Taken together, our results unveiled that low dose PFDA can cause deleterious effects on DNA and DNA damage repair (DDR) in ovarian epithelial cells and induce genomic instability.