Discovering transformation products of pharmaceuticals in domestic wastewaters and receiving rivers by using non-target screening and machine learning approaches.

Wastewater treatment plants (WWTPs) are an important source of pharmaceuticals in surface water, but information about their transformation products (TPs) is very limited. Here, we investigated occurrence and transformation of pharmaceuticals and TPs in WWTPs and receiving rivers by using suspect and non-target analysis as well as target analysis. Results showed identification of 113 pharmaceuticals and 399 TPs, including mammalian metabolites (n = 100), environmental microbial degradation products (n = 250), photodegradation products (n = 44) and hydrolysis products (n = 5). The predominant parent pharmaceuticals (n = 37) and transformation products (n = 68) were mainly derived from antimicrobials, accounting for 32.7 % and 17.0 %, respectively. The identified compounds were found in the influent (387-428) and effluent (227-400) of WWTPs, as well as upstream (290-451) and downstream (322-416) of receiving rivers, most predominantly from antimicrobials, followed by analgesic and antipyretic drugs. A total of 399 identified TPs were transformed by 110 pathways, of which the oxidation reaction was predominant (27.0 %), followed by photodegradation reaction (10.7 %). Of the 399 TPs, 49 (with lower PNECs) were predicted to be more toxic than their parents. Compounds with potential high risks (hazard quotient >1 and risk index (RI) > 0.1) were found in the WWTP influent (126), effluent (53) and river (61), and the majority were from the antimicrobial and antihypertensive classes. In particular, the potential risks (RI) of TPs from roxithromycin and irbesartan were found higher than those for their corresponding parents. The findings from this study highlight the need to monitor TPs from pharmaceuticals in the environment.

Progress in SARS-CoV-2, diagnostic and clinical treatment of COVID-19.

Background: Corona Virus Disease 2019(COVID-19)is a global pandemic novel coronavirus infection disease caused by Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although rapid, large-scale testing plays an important role in patient management and slowing the spread of the disease. However, there has been no good and widely used drug treatment for infection and transmission of SARS-CoV-2. Key findings: Therefore, this review updates the body of knowledge on viral structure, infection routes, detection methods, and clinical treatment, with the aim of responding to the large-section caused by SARS-CoV-2. This paper focuses on the structure of SARS-CoV-2 viral protease, RNA polymerase, serine protease and main proteinase-like protease as well as targeted antiviral drugs. Conclusion: In vitro or clinical trials have been carried out to provide deeper thinking for the pathogenesis, clinical diagnosis, vaccine development and treatment of SARS-CoV-2.

Non-target discovery and risk prediction of per- and polyfluoroalkyl substances (PFAS) and transformation products in wastewater treatment systems.

Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1-3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.

An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.

Altered static and dynamic functional network connectivity in individuals with subthreshold depression: a large-scale resting-state fMRI study.

Dynamic functional network connectivity (dFNC) is an expansion of static FNC (sFNC) that reflects connectivity variations among brain networks. This study aimed to investigate changes in sFNC and dFNC strength and temporal properties in individuals with subthreshold depression (StD). Forty-two individuals with subthreshold depression and 38 healthy controls (HCs) were included in this study. Group independent component analysis (GICA) was used to determine target resting-state networks, namely, executive control network (ECN), default mode network (DMN), sensorimotor network (SMN) and dorsal attentional network (DAN). Sliding window and k-means clustering analyses were used to identify dFNC patterns and temporal properties in each subject. We compared sFNC and dFNC differences between the StD and HCs groups. Relationships between changes in FNC strength, temporal properties, and neurophysiological score were evaluated by Spearman's correlation analysis. The sFNC analysis revealed decreased FNC strength in StD individuals, including the DMN-CEN, DMN-SMN, SMN-CEN, and SMN-DAN. In the dFNC analysis, 4 reoccurring FNC patterns were identified. Compared to HCs, individuals with StD had increased mean dwell time and fraction time in a weakly connected state (state 4), which is associated with self-focused thinking status. In addition, the StD group demonstrated decreased dFNC strength between the DMN-DAN in state 2. sFNC strength (DMN-ECN) and temporal properties were correlated with HAMD-17 score in StD individuals (all p < 0.01). Our study provides new evidence on aberrant time-varying brain activity and large-scale network interaction disruptions in StD individuals, which may provide novel insight to better understand the underlying neuropathological mechanisms.

Boosting electrocatalytic ammonia synthesis from nitrate by asymmetric chemical potential activated interfacial electric fields.

The electrocatalytic nitrate reduction reaction (NO3- RR) has immense potential to alleviate the problem of groundwater pollution and may also become a key route for the environmentally benign production of ammonia (NH3) products. Here, the unique effects of interfacial electric fields arising from asymmetric chemical potentials and local defects were integrated into the binary Bi2S3-Bi2O3 sublattices for enhancing electrocatalytic nitrate reduction reactions. The obtained binary system showed a superior Faraday efficiency (FE) for ammonia production of 94 % and an NH3 yield rate of 89.83 mg gcat-1h-1 at -0.4 V vs. RHE. Systematic experimental and computational results confirmed that the concerted interplay between interfacial electric fields and local defects not only promoted the accumulation and adsorption of NO3-, but also contributed to the destabilization of *NO and the subsequent deoxygenation hydrogenation reaction. This work will stimulate future designs of heterostructured catalysts for efficient electrocatalytic nitrate reduction reactions.

Preparation of GO/COFs composites by interlayer-confined strategy for the adsorption of nitro aromatic pollutants.

With the continuous development of industrialization, the excessive emission of nitro aromatic with strong toxicity, high carcinogenicity and non-degradability has attracted great attention. How to efficiently remove nitro aromatic pollutants is an important research topic. In this work, graphene oxide/covalent organic frameworks (GO/COFs) composites were successfully synthesized via interlayer confinement strategy selecting GO, 2,5-dimethoxybenzene-1,4-dicarboxaldehyde (DMTP) and 1,3,5-tri(4-aminophenyl)benzene (TPB) as raw materials. Due to high specific surface area, hierarchical porous structure and good thermal stability, GO/COFs were utilized to adsorb and remove nitro aromatic hydrocarbons in the water environment. The adsorption behavior of GO/COFs for o-nitrophenol, 1,3-dinitrobenzene and 2,4,6-trinitrophenol were further investigated. The GO/COFs composites showed the strongest adsorption capacity for 2,4,6-trinitrophenol, and the maximum adsorption capacity for 2,4,6-trinitrophenol, o-nitrophenol, and 1,3-dinitrobenzene were 438, 317, and 173 mg g-1, respectively. The experimental results indicated that the GO/COFs composites provided great adsorption capability for nitro aromatic pollutants and can be reused, rendering it an extremely potential adsorbent for organic pollutants.

Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.

Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

Analysis of PIK3CA mutations in the primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative breast cancer.

OBJECTIVE: Our aim was to compare the PIK3CA mutation status in matched primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) to gain insight into the optimization of patient selection and detection time for PIK3CA-targeted therapy. METHODS: The data were from 3035 patients with BC diagnosed at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2017. Matched primary and recurrent samples were profiled using amplification-refractory mutation system-polymerase chain reaction covering 11 mutational hotspots in PIK3CA. RESULTS: PIK3CA mutations were detected in 54.3% primary tumors and 48.6% corresponding recurrences. PIK3CA mutation was detected in 37.5% cases in the locoregional recurrent group and 40.0% of distant metastasis, without a statistical difference. Besides, PIK3CA mutations were concordant in 88.6% of the matched pairs. For patients treated with neoadjuvant chemotherapy, 100% concordance was observed. However, PIK3CA mutation was neither correlated with clinicopathological features nor associated with clinical outcomes. CONCLUSIONS: Mutations in PIK3CA in HR+/HER2- BC generally progressed to recurrent tumors. The high concordance rate of PIK3CA mutation status between primary tumors and corresponding recurrences suggests that the detection of primary tumors could be a substitute approach when recurrent samples are not easily obtainable.

Identification of clear cell renal cell carcinoma subtypes by integrating radiomics and transcriptomics.

Objective: This study aimed to delineate the clear cell renal cell carcinoma (ccRCC) intrinsic subtypes through unsupervised clustering of radiomics and transcriptomics data and to evaluate their associations with clinicopathological features, prognosis, and molecular characteristics. Methods: Using a retrospective dual-center approach, we gathered transcriptomic and clinical data from ccRCC patients registered in The Cancer Genome Atlas and contrast-enhanced computed tomography images from The Cancer Imaging Archive and local databases. Following the segmentation of images, radiomics feature extraction, and feature preprocessing, we performed unsupervised clustering based on the "CancerSubtypes" package to identify distinct radiotranscriptomic subtypes, which were then correlated with clinical-pathological, prognostic, immune, and molecular characteristics. Results: Clustering identified three subtypes, C1, C2, and C3, each of which displayed unique clinicopathological, prognostic, immune, and molecular distinctions. Notably, subtypes C1 and C3 were associated with poorer survival outcomes than subtype C2. Pathway analysis highlighted immune pathway activation in C1 and metabolic pathway prominence in C2. Gene mutation analysis identified VHL and PBRM1 as the most commonly mutated genes, with more mutated genes observed in the C3 subtype. Despite similar tumor mutation burdens, microsatellite instability, and RNA interference across subtypes, C1 and C3 demonstrated greater tumor immune dysfunction and rejection. In the validation cohort, the various subtypes showed comparable results in terms of clinicopathological features and prognosis to those observed in the training cohort, thus confirming the efficacy of our algorithm. Conclusion: Unsupervised clustering based on radiotranscriptomics can identify the intrinsic subtypes of ccRCC, and radiotranscriptomic subtypes can characterize the prognosis and molecular features of tumors, enabling noninvasive tumor risk stratification.

Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study.

Background: The application of radiofrequency ablation (RFA) is becoming increasingly widespread in the treatment of primary hyperparathyroidism (PHPT). However, the effect of RFA treatment on the skeleton in mild PHPT remains unclear. Therefore, the aim of this study was to investigate the change in bone turnover markers and bone mineral density (BMD) before and 2 years after RFA in patients with mild PHPT. Methods: In this open-label, prospective study, 81 patients with mild PHPT including 36 treated with RFA and 45 observed without intervention (OBS), along with 81 age-matched healthy controls, were enrolled from November 2018 to September 2021 at Gansu Provincial Hospital. The main outcome measures were levels of serum calcium, serum intact parathyroid hormone (iPTH), and bone turnover markers, including bone-specific alkaline phosphatase (ALP), C-terminal cross-linking telopeptides of type I collagen (ß-CTx), and osteocalcin (OC). BMD (femoral neck and lumbar spine) was measured with dual-energy X-ray absorptiometry, and spine radiographs were obtained for vertebral fracture assessment. Paired and unpaired two-tailed t-tests and Spearman rank correlation coefficient were used for statistical analyses. Results: Normalized outcomes for both iPTH and calcium levels were achieved in 32 of 36 (88.9%) patients with mild PHPT treated with RFA. There was a significant treatment effect of RFA on bone turnover biomarkers compared with OBS before the treatment (P=0.04) and at the end of follow-up or (P=0.03). BMD of the lumbar spine increased by 1.8% (P=0.03) and remained stable in the femoral neck (P=0.17) after RFA. However, there was an obvious treatment effect of RFA on BMD compared with OBS (P 0.04). The only compartment with a T-score increase in the RFA group was the lumbar spine in (P<0.001). There was no difference in fracture frequency between groups during the follow-up period. Conclusions: RFA can improve serum bone turnover markers in patients with mild PHPT and can be expected to increase BMD in the L1-L4 vertebrae and preserve BMD in the femoral neck. Whether RFA can reduce fracture risk in the long-term is a clinical concern for patients with mild PHPT.

The mechanism of resveratrol stabilization and degradation by synergistic interactions between constituent proteins of whey protein.

Whey protein isolate (WPI) is mainly composed of ß-lactoglobulin (ß-LG), α-lactalbumin (α-LA) and bovine serum albumin (BSA). The aim of this study was to compare and analyze the influence of WPI and its three main constituent proteins, as well as proportionally reconstituted WPI (R-WPI) on resveratrol. It was found that the storage stability of resveratrol was protected by WPI, not affected by R-WPI, but reduced by individual whey proteins at 45°C for 30 days. The rank of accelerated degradation of resveratrol by individual whey proteins was BSA > α-LA > ß-LG. The antioxidant activity, localization of resveratrol and oxidation of carrier proteins were determined by ABTS, H2O2 assay, synchronous fluorescence, carbonyl and circular dichroism. The non-covalent interactions and disulfide bonds between constituent proteins improved the antioxidant activity of the R-WPI-resveratrol complex, the oxidation stability of the carrier and the solvent shielding effect on resveratrol, which synergistically inhibited the degradation of resveratrol in R-WPI system. The results gave insight into elucidating the interaction mechanism of resveratrol with protein carriers.

Prediction of blood-brain barrier permeability using machine learning approaches based on various molecular representation.

The assessment of compound blood-brain barrier (BBB) permeability poses a significant challenge in the discovery of drugs targeting the central nervous system. Conventional experimental approaches to measure BBB permeability are labor-intensive, cost-ineffective, and time-consuming. In this study, we constructed six machine learning classification models by combining various machine learning algorithms and molecular representations. The model based on ExtraTree algorithm and random partitioning strategy obtains the best prediction result, with AUC value of 0.932±0.004 and balanced accuracy (BA) of 0.837±0.010 for the test set. We employed the SHAP method to identify important features associated with BBB permeability. In addition, matched molecular pair (MMP) analysis and representative substructure derivation method were utilized to uncover the transformation rules and distinctive structural features of BBB permeable compounds. The machine learning models proposed in this work can serve as an effective tool for assessing BBB permeability in the drug discovery for central nervous system disease.

Unveiling major histocompatibility complex-mediated pan-cancer immune features by integrated single-cell and bulk RNA sequencing.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet persistent challenges such as low response rate and significant heterogeneity necessitate attention. The pivotal role of the major histocompatibility complex (MHC) in ICI efficacy, its intricate impacts and potentials as a prognostic marker, warrants comprehensive exploration. This study integrates single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and spatial transcriptomic analyses to unveil pan-cancer immune characteristics governed by the MHC transcriptional feature (MHC.sig). Developed through scRNA-seq analysis of 663,760 cells across diverse cohorts and validated in 30 solid cancer types, the MHC.sig demonstrates a robust correlation between immune-related genes and infiltrating immune cells, highlighting its potential as a universal pan-cancer marker for anti-tumor immunity. Screening the MHC.sig for therapeutic targets using CRISPR data identifies potential genes for immune therapy synergy and validates its predictive efficacy for ICIs responsiveness across diverse datasets and cancer types. Finally, analysis of cellular communication patterns reveals interactions between C1QC+macrophages and malignant cells, providing insights into potential therapeutic agents and their sensitivity characteristics. This comprehensive analysis positions the MHC.sig as a promising marker for predicting immune therapy outcomes and guiding combinatorial therapeutic strategies.

Pt(IV) Prodrug Photoactivation: A Promising Strategy for Cancer Therapy.

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, next the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.

Flexible Multicavity SERS Substrate Based on Ag Nanoparticle-Decorated Aluminum Hydrous Oxide Nanoflake Array for Highly Sensitive In Situ Detection.

Flexible surface-enhanced Raman scattering (SERS) substrates are very promising to meet the needs for real-time and on-field detection in practical applications. However, high-performance flexible SERS substrates often suffer from complexity and high cost in fabrication, limiting their widespread applications. Herein, we developed a facile method to fabricate a flexible multicavity SERS substrate composed of a silver nanoparticle (AgNP)-decorated aluminum hydrous oxide nanoflake array (NFA) grown on a polydimethylsiloxane (PDMS) membrane. Strong plasmon couplings promoted by multiple nanocavities afford high-density hotspots within such a flexible AgNPs@NFA/PDMS film, boosting high SERS sensitivity with an enhancement factor (EF) of ∼1.54 × 109, and a limit of detection (LOD) of ∼7.4 × 10-13 M for rhodamine 6G (R6G) molecules. Furthermore, benefiting from the high sensitivity, high mechanical stability, and transparency of this substrate, in situ SERS detections of trace thiram and crystal violet (CV) molecules on the surface of cherry tomatoes and fish have been realized, with LODs much lower than the maximum allowable limit in food, demonstrating the great potential of such a flexible substrate in food safety monitoring. More importantly, the preparation processes are very simple and environmentally friendly, and the techniques involved are completely compatible with well-established silicon device technologies. Therefore, large-area fabrication with low cost can be readily realized, enabling the extensive applications of SERS sensors in daily life.

Enhanced adsorption of phosphate by rice straw-based biochar prepared via metal impregnation and bio-template technology.

Phosphate removal from water through green, highly efficient technologies has received much attention. Biochar is an effective adsorbent for phosphate removal. However, adsorption capacity of phosphate on pristine rice straw-based biochar was not optimistic due to low anion exchange capacity. In this study, Fe-modified, Mg-modified and MgFe-modified rice straw-based biochar (Fe-BC, Mg-BC and MgFe-BC) were prepared by combining metal impregnation and biological template methods to improve the adsorption capacity of phosphate. The surface characteristics of biochar and the adsorption behavior of phosphate on biochar were investigated. The modified biochar had the specific surface area of 17.910-39.336 m2/g, and their surfaces were rich in a large number of functional groups and metal oxides. Phosphate release was observed on pristine rice straw-based biochar without metal impregnation. The maximum adsorption capacities of phosphate on MgFe-BC, Mg-BC and Fe-BC at 298 K were 6.93, 5.75 and 0.23 mg/g, respectively. Adsorption was a spontaneous endothermic process, while chemical adsorption dominated and electrostatic attraction and pores filling existed simultaneously. Based on the site energy distribution theory study, the standard deviation of MgFe-BC decreased from 6.96 to 4.64 kJ/mol with temperature increasing, which proved that the higher the temperature would cause the lower heterogeneity. Moreover, the effects of pH, humic acid, co-existing ions and ionic strength on phosphate adsorption of MgFe-BC were also discussed. MgFe-BC with fine pores and efficient adsorption sites is an ideal adsorbent for phosphate removal from water.

Pharmacological elevation of glutathione inhibits status epilepticus-induced neuroinflammation and oxidative injury.

Glutathione (GSH) is a major endogenous antioxidant, and its depletion has been observed in several brain diseases including epilepsy. Previous studies in our laboratory have shown that dimercaprol (DMP) can elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme and inhibit neuroinflammation in vitro. Here we determined 1) the role of cysteamine as a new mechanism by which DMP increases GSH biosynthesis and 2) its ability to inhibit neuroinflammation and neuronal injury in the rat kainate model of epilepsy. DMP depleted cysteamine in a time- and concentration-dependent manner in a cell free system. To guide the in vivo administration of DMP, its pharmacokinetic profile was determined in the plasma, liver, and brain. The results confirmed DMP's ability to cross the blood-brain-barrier. Treatment of rats with DMP (30 mg/kg) depleted cysteamine in the liver and hippocampus that was associated with increased GCL activity in these tissues. GSH levels were significantly increased (20 %) in the hippocampus 1 h after 30 mg/kg DMP administration. Following DMP (30 mg/kg) administration once daily, a marked attenuation of GSH depletion was seen in the SE model. SE-induced inflammatory markers including cytokine release, microglial activation, and neuronal death were significantly attenuated in the hippocampus with DMP treatment. Taken together, these results highlight the importance of restoring redox status with rescue of GSH depletion by DMP in post epileptogenic insults.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.