Clinical application of the free superficial palmar branch of radial artery flap for soft-tissue reconstruction of distal digital injury.

PURPOSE: The purpose of this study is to retrospect and summarize clinical efficiency and experience of the free superficial palmar branch of radial artery (SPBRA) flap for soft-tissue reconstruction in distal digital injury. METHOD: 13 patients with soft-tissue defect of finger, reconstructed by the free superficial palmar branch of radial artery (SPBRA) flap in our department from January 2020 to January 2022, were reviewed. After 6-12 months of follow-up, evaluated the treatment effect of the fingers reconstructed by SPBRA flap. RESULTS: All the flaps in our series application were survival uneventful, and all the donor sites were closed primarily without complications or obvious scarring. The flaps were soft in texture and satisfactory in appearance and function. The flaps with the median nerve palmar cutaneous branch had a good sensation recovery. Measurement of two-point discrimination (TPD) ranged from 6 to 10 mm. All patients were satisfied with the aesthetic appearance. According to the Evaluation Trial Standards of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, the results were graded as excellent in 11 cases and good in 2 cases. CONCLUSION: The SPBRA perforator flap has the advantages of simple operation, soft texture, good appearance and function, and is credible and useful for reconstructing various finger injuries.

Diagnostic accuracy of artificial intelligence-assisted caries detection: a clinical evaluation.

OBJECTIVE: This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images. METHODS: In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard. RESULTS: The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%). CONCLUSION: The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice.

Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage "eat me" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.

Fe-O4 Motif Activated Graphitic Carbon via Oxo-Bridge for Highly Selective H2O2 Electrosynthesis.

Carbon-based materials have been utilized as effective catalysts for hydrogen peroxide electrosynthesis via two-electron oxygen reduction reaction (2e ORR), however the insufficient selectivity and productivity still hindered the further industrial applications. In this work, we report the Fe-O4 motif activated graphitic carbon material which enabled highly selective H2O2 electrosynthesis operating at high current density with excellent anti-poisoning property. In the bulk production test, the concentration of H2O2 cumulated to 8.6 % in 24 h and the corresponding production rate of 33.5 mol gcat -1 h-1 outperformed all previously reported materials. Theoretical model backed by in situ characterization verified α-C surrounding the Fe-O4 motif as the actual reaction site in terms of thermodynamics and kinetics aspects. The strategy of activating carbon reaction site by metal center via oxo-bridge provides inspiring insights for the rational design of carbon materials for heterogeneous catalysis.

Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI). Unfortunately, a majority of these patients develop therapeutic resistance with progression free survival lasting 9-18 months. The mechanisms that underlie the tumorigenic effects of EGFR and the ability of NSCLC to develop resistance to TKI therapies, however, are poorly understood. Here we demonstrate that CHI3L1 is produced by EGFR activation of normal epithelial cells, transformed epithelial cells with wild type EGFR and cells with cancer-associated, activating EGFR mutations. We also demonstrate that CHI3L1 auto-induces itself and feeds back to stimulate EGFR and its ligands via a STAT3-dependent mechanism(s). Highly specific antibodies against CHI3L1 (anti-CHI3L1/FRG) and TKI, individually and in combination, abrogated the effects of EGFR activation on CHI3L1 and the ability of CHI3L1 to stimulate the EGFR axis. Anti-CHI3L1 also interacted with osimertinib to reverse TKI therapeutic resistance and induce tumor cell death and inhibit pulmonary metastasis while stimulating tumor suppressor genes including KEAP1. CHI3L1 is a downstream target of EGFR that feeds back to stimulate and activate the EGFR axis. Anti-CHI3L1 is an exciting potential therapeutic for EGFR mutant NSCLC, alone and in combination with osimertinib or other TKIs.

Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel.

Purpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.

Maize Dek51 encodes a DEAD-box RNA helicase essential for pre-rRNA processing and seed development.

Pre-rRNA processing is essential to ribosome biosynthesis. However, the processing mechanism is not fully understood in plants. Here, we report a DEAD-box RNA helicase DEK51 that mediates the 3' end processing of 18S and 5.8S pre-rRNA in maize (Zea mays L.). DEK51 is localized in the nucleolus, and loss of DEK51 arrests maize seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA. DEK51 interacts with putative key factors in nuclear RNA exosome-mediated pre-rRNA processing, including ZmMTR4, ZmSMO4, ZmRRP44A, and ZmRRP6L2. This suggests that DEK51 facilitates pre-rRNA processing by interacting with the exosome. Loss of ZmMTR4 function arrests seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA, similar to dek51. DEK51 also interacts with endonucleases ZmUTP24 and ZmRCL1, suggesting that it may also be involved in the cleavage at site A2. These results show the critical role of DEK51 in promoting 3' end processing of pre-rRNA.

Response of soil moisture to rainfall following deep soil drying in China's hilly loess lands.

Deep soil drying is a physical soil phenomenon that has become increasingly characteristic to artificial afforestation on China's Loess Plateau. Current research is largely short of conclusive reports on soil moisture recovery following deep soil drying in afforested lands. In this study, a 10-m deep underground column was constructed at Pengyang Experimental Station in Ningxia. The CS650-CR1000 automatic soil moisture monitoring system and BLJW-4 small meteorological observation stations were used to respectively monitor soil moisture and meteorological conditions in the study area for the period 2014-2019. The local rainfall was classified and the characteristics of soil infiltration analyzed at both monthly and annual scales. The results showed that: i) Deep soil moisture recovery in the semi-arid Loess Plateau region depended mainly on 25-49.9 mm and >50 mm types of rainfall; together accounting for 35.44 % of the precipitation. ii) Deep soil moisture replenishment occurred mainly for the period from April to October. While this accounted for 30.13 % of the precipitation, evaporation loss accounted for 69.87 % of it. With increasing monthly rainfall (Pm), the variation in monthly infiltration depth (Zm) was quadratic in shape - where Zm = -0.0094 Pm2 + 3.7702 Pm (R2 = 0.9577). iii) At the annual scale, deep soil moisture replenishment was mainly driven by year-on-year infiltration water accumulation. This is because a single year precipitation infiltration was not enough to replenish deep soil moisture. The cumulative infiltration depth for 2014-2019 was 180, 260, 400, 700, 1000 > 1000 cm. It suggested that soil water infiltration and deep dry soil recovery occurred at different times under rainfed conditions in the semi-arid loess hills in China. This is key for in-depth studies of the hydrological process in dry soil regions.

Seasonal variations in soil microbial community co-occurrence network complexity respond differently to field-simulated warming experiments in a northern subtropical forest.

Global warming may reshape seasonal changes in microbial community diversity and co-occurrence network patterns, with significant implications for terrestrial ecosystem function. We conducted a 2-year in situ field simulation of the effects of warming on the seasonal dynamics of soil microbial communities in a northern subtropical Quercus acutissima forest. Our study revealed that warming had no significant effect on the richness or diversity of soil bacteria or fungi in the growing season, whereas different warming gradients had different effects on their diversity in the nongrowing season. Warming also changed the microbial community structure, increasing the abundance of some thermophilic microbial species and decreasing the abundance of some symbiotrophic microorganisms. The co-occurrence network analysis of the microbial community showed that warming decreased the complexity of the intradomain network in the soil bacterial community in the growing and nongrowing seasons but increased it in the fungal community. Moreover, increasing warming temperatures increased the complexity of the interdomain network between bacteria and fungi in the growing season but decreased it in the nongrowing season, and the keystone species in the interdomain network changed with warming. Warming also reduced the proportion of positive microbial community interactions, indicating that warming reduced the mutualism, commensalism, and neutralism of microorganisms as they adapted to soil environmental stress. The factors affecting the fungal community varied considerably across warming gradients, with the bacterial community being significantly affected by soil temperature, MBC, NO3--N and NH4+-N, moreover, SOC and TN significantly affected fungal communities in the 4 °C warming treatment. These results suggest that warming increases seasonal differences in the diversity and complexity of soil microbial communities in the northern subtropical region, significantly influencing soil dynamic processes regulating forest ecosystems under global warming.

Risks associated with cognitive function and management strategies in the clinical use of ADT: a systematic review from clinical and preclinical studies.

Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT.

Ultrafine Asymmetric Soft/Stiff Nanohybrids with Tunable Patchiness via a Dynamic Surface-Mediated Assembly.

Asymmetric soft-stiff patch nanohybrids with small size, spatially separated organics and inorganics, controllable configuration, and appealing functionality are important in applications, while the synthesis remains a great challenge. Herein, based on polymeric single micelles (the smallest assembly subunit of mesoporous materials), we report a dynamic surface-mediated anisotropic assembly approach to fabricate a new type of small asymmetric organic/inorganic patch nanohybrid for the first time. The size of this asymmetric organic/inorganic nanohybrid is ∼20 nm, which contains dual distinct subunits of a soft organic PS-PVP-PEO single micelle nanosphere (12 nm in size and 632 MPa in Young' modulus) and stiff inorganic SiO2 nanobulge (∼8 nm, 2275 MPa). Moreover, the number of SiO2 nanobulges anchored on each micelle can be quantitatively controlled (from 1 to 6) by dynamically tuning the density (fluffy or dense state) of the surface cap organic groups. This small asymmetric patch nanohybrid also exhibits a dramatically enhanced uptake level of which the total amount of intracellular endocytosis is about three times higher than that of the conventional nanohybrids.

Impact of Lime Saturation Factor on Alite-Ye'Elimite Cement Synthesis and Hydration.

Alite(C3S)-Ye'elimite(C4A3$) cement is a high cementitious material that incorporates a precise proportion of ye'elimite into the ordinary Portland cement. The synthesis and hydration behavior of Alite-Ye'elimite clinker with different lime saturation factors were investigated. The clinkers were synthesized using a secondary thermal treatment process, and their compositions were characterized. The hydrated pastes were analyzed for their hydration products, pore structure, mechanical strength, and microstructure. The clinkers and hydration products were characterized using XRD, TG-DSC, SEM, and MIP analysis. The results showed that the Alite-Ye'elimite cement clinker with a lime saturation factor (KH) of 0.93, prepared through secondary heat treatment, contained 64.88% C3S and 2.06% C4A3$. At this composition, the Alite-Ye'elimite cement clinker demonstrated the highest 28-day strength. The addition of SO3 to the clinkers decreased the content of tricalcium aluminate (C3A) and the ratio of Alite/Belite (C3S/C2S), resulting in a preference for belite formation. The pore structure of the hydrated pastes was also investigated, revealing a distribution of pore sizes ranging from 0.01 to 10 µm, with two peaks on each differential distribution curve corresponding to micron and sub-micron pores. The pore volume decreased from 0.22 ± 0.03 to 0.15 ± 0.18 cm3 g-1, and the main peak of pore distribution shifted towards smaller sizes with increasing hydration time.

Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study.

OBJECTIVES: To estimate the burden, trends, and inequalities of type 1 diabetes mellitus (T1DM) among older adults at global, regional, and national level from 1990 to 2019. DESIGN: Population based study. POPULATION: Adults aged ≥65 years from 21 regions and 204 countries and territories (Global Burden of Disease and Risk Factors Study 2019)from 1990 to 2019. MAIN OUTCOME MEASURES: Primary outcomes were T1DM related age standardised prevalence, mortality, disability adjusted life years (DALYs), and average annual percentage change. RESULTS: The global age standardised prevalence of T1DM among adults aged ≥65 years increased from 400 (95% uncertainty interval (UI) 332 to 476) per 100 000 population in 1990 to 514 (417 to 624) per 100 000 population in 2019, with an average annual trend of 0.86% (95% confidence interval (CI) 0.79% to 0.93%); while mortality decreased from 4.74 (95% UI 3.44 to 5.9) per 100 000 population to 3.54 (2.91 to 4.59) per 100 000 population, with an average annual trend of -1.00% (95% CI -1.09% to -0.91%), and age standardised DALYs decreased from 113 (95% UI 89 to 137) per 100 000 population to 103 (85 to 127) per 100 000 population, with an average annual trend of -0.33% (95% CI -0.41% to -0.25%). The most significant decrease in DALYs was observed among those aged <79 years: 65-69 (-0.44% per year (95% CI -0.53% to -0.34%)), 70-74 (-0.34% per year (-0.41% to -0.27%)), and 75-79 years (-0.42% per year (-0.58% to -0.26%)). Mortality fell 13 times faster in countries with a high sociodemographic index versus countries with a low-middle sociodemographic index (-2.17% per year (95% CI -2.31% to -2.02%) v -0.16% per year (-0.45% to 0.12%)). While the highest prevalence remained in high income North America, Australasia, and western Europe, the highest DALY rates were found in southern sub-Saharan Africa, Oceania, and the Caribbean. A high fasting plasma glucose level remained the highest risk factor for DALYs among older adults during 1990-2019. CONCLUSIONS: The life expectancy of older people with T1DM has increased since the 1990s along with a considerable decrease in associated mortality and DALYs. T1DM related mortality and DALYs were lower in women aged ≥65 years, those living in regions with a high sociodemographic index, and those aged <79 years. Management of high fasting plasma glucose remains a major challenge for older people with T1DM, and targeted clinical guidelines are needed.

The Influence of Retreated Lithium Slag with a High Content of Alkali, Sulfate and Fluoride on the Composition and the Microstructure of Autoclaved Aerated Concrete.

In this paper, the possibility of retreated lithium slag (RTLS) with a high content of alkali, sulfate and fluoride as a partial replacement for fly ash (FA) to produce autoclaved aerated concrete (AAC) was investigated. The influence of the RTLS dosage on the AAC performance were examined. The composition and microstructure of hydrates as well as the microstructure of the RTLS-FA-based AAC compositions were determined by XRD, FTIR, TG-DSC and SEM. The results illustrated that the incorporation of RTLS changed the crystal structure and the microstructure of the tobermorite. With increased RTLS contents, the morphology of tobermorite was changed, and the grass-like tobermorite gradually transformed into network-like tobermorite. The newly formed tobermorite improved the mechanical performance of the AAC. Compared with the RTLS10, the content of tobermorite in the RTLS30 increased by 8.6%.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

Enhancing clinical utility: deep learning-based embryo scoring model for non-invasive aneuploidy prediction.

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.