Redox-neutral electrochemical decontamination of hypersaline wastewater with high technology readiness level.

Industrial hypersaline wastewaters contain diverse pollutants that harm the environment. Recovering clean water, alkali and acid from these wastewaters can promote circular economy and environmental protection. However, current electrochemical and advanced oxidation processes, which rely on hydroxyl radicals to degrade organic compounds, are inefficient and energy intensive. Here we report a flow-through redox-neutral electrochemical reactor (FRER) that effectively removes organic contaminants from hypersaline wastewaters via the chlorination-dehalogenation-hydroxylation route involving radical-radical cross-coupling. Bench-scale experiments demonstrate that the FRER achieves over 75% removal of total organic carbon across various compounds, and it maintains decontamination performance for over 360 h and continuously treats real hypersaline wastewaters for two months without corrosion. Integrating the FRER with electrodialysis reduces operating costs by 63.3% and CO2 emissions by 82.6% when compared with traditional multi-effect evaporation-crystallization techniques, placing our system at technology readiness levels of 7-8. The desalinated water, high-purity NaOH (>95%) and acid produced offset industrial production activities and thus support global sustainable development objectives.

A pharmacovigilance study of adverse events associated with polymyxins based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

BACKGROUND: Polymyxins have been regarded as last-line treatment for multidrug-resistant gram-negative bacterial infections. Nonetheless, concerns regarding toxicity persist. This study aimed to explore and compare potential adverse events (AEs) between colistin and polymyxin B (PMB). METHODS: Outpatient antibiotic use associated with acute upper respiratory infections in China: a nationwide cross-sectional study Polymyxins-related AEs were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System between 2004 and 2022. Potential signals were estimated by the reporting odds ratio (ROR), and subgroup analyses were preformed to adjust for potential factors in AEs with significant disproportionality. RESULTS: Analysis of 3,915 records involving 718 patients revealed a higher disproportionality of renal and urinary disorders (ROR 1.62, 95% CI 1.01-2.59) and acute kidney injury (ROR 1.75, 95% CI 1.07-2.87) with colistin treatment. Conversely, colistin exhibited a lower risk for neurotoxicity (ROR 0.47, 95% CI 0.30-0.73). Seven cases of skin hyperpigmentation were reported with PMB, whereas none were reported with colistin. Over 80% of cases involving polymyxin-related AEs occurred during the first two weeks of therapies, with a median onset time of 4.5 days. CONCLUSIONS: Outpatient antibiotic use associated with acute upper respiratory infections in China: a nationwide cross-sectional study Patients received colistin displayed a higher potential risk of nephrotoxicity but a lower risk of neurotoxicity. Clinicians should be vigilant in monitoring the AEs of hyperpigmentation disorders induced by PMB.

Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10†241 Patients in China.

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15 166 patients, of which 10 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.

MoOxNWs with mechanical damage - oriented synergistic photothermal / photodynamic therapy for highly effective treating wound infections.

Reactive oxygen species (ROS)-based therapy has emerged as a promising antibacterial strategy. However, it faces the limitations of uncontrollable space-time release and excessive lipid peroxidation, which may lead to a series of metabolic disorders and decreased immune function. In this study, mechanical damage by molybdenum oxide nanowires (MoOxNWs) is introduced as a synergistic factor to enhance the photothermal and photodynamic effects for controllable and efficient antibacterial therapy. Through their sharp ends, the nanowires can effectively pierce and damage the bacterial cells, thus facilitating the entry of externally generated ROS into the cells. The ROS are generated via photodynamic effect of the nanowires under a mere 5 min of near-infrared light irradiation. This approach enhances the photothermal (by 27.3 %) and photodynamic properties of ROS generation. MoOxNWs (100 µg·mL-1) achieve sterilisation rates of 97.67 % for extended-spectrum ß-lactamase-producing E. coli and 96.34 % for methicillin-resistant Staphylococcus aureus, which are comparable or even exceeding the efficacy of most MoOx-based antibacterial agents. Moreover, they exhibit good biocompatibility and low in vivo toxicity.

Pregnancy-related adverse events associated with statins: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications. RESEARCH DESIGN AND METHODS: Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab). RESULTS: A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22-4.95; IC025 = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65-6.54; IC025 = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56-16.56; IC025 = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab. CONCLUSIONS: Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.

Defect-Engineering-Mediated Long-Lived Charge-Transfer Excited-State in Fe-Gallate Complex Improves Iron Cycle and Enables Sustainable Fenton-Like Reaction.

Fenton reactions are inefficient because the Fe(II) catalyst cannot be recycled in time due to the lack of a rapid electron transport pathway. This results in huge H2 O2 wastage in industrial applications. Here, it is shown that a sustainable heterogeneous Fenton system is attainable by enhancing the ligand-to-metal charge-transfer (LMCT) excited-state lifetime in Fe-gallate complex. By engineering oxygen defects in the complex, the lifetime is improved from 10-90 ps. The lengthened lifetime ensures sufficient concentrations of excited-states for an efficient Fe cycle, realizing previously unattainable H2 O2 activation kinetics and hydroxyl radical (• OH) productivity. Spectroscopic and electrochemical studies show the cyclic reaction mechanism involves in situ Fe(II) regeneration and synchronous supply of oxygen atoms from water to recover dissociated Fe─O bonds. Trace amounts of this catalyst effectively destroy two drug-resistant bacteria even after eight reaction cycles. This work reveals the link among LMCT excited-state lifetime, Fe cycle, and catalytic activity and stability, with implications for de novo design of efficient and sustainable Fenton-like processes.

A Nano-Autophagy Inhibitor Triggering Reciprocal Feedback Control of Cholesterol Depletion for Solid Tumor Therapy.

Solid tumors are characterized by enhanced metabolism of lipid, particularly cholesterol, inspiring the exploration of metabolic therapy through cholesterol oxidase (COD)-mediated cholesterol deprivation. However, the therapeutic efficacy of COD is limited due to the hypoxic tumor microenvironment and the protective autophagy triggered by cholesterol deprivation. Herein, a combination therapy for metabolically treating solid tumors through COD in conjunction with molybdenum oxide nanodots (MONDs), which serve as both potent oxygen generators and autophagy inhibitors, is reported. MONDs convert H2 O2 (arising from COD-mediated cholesterol oxidation) into O2 , which is then recycled by COD to form reciprocal feedback for cholesterol depletion. Concurrently, MONDs can overcome autophagy-induced therapeutic resistance frequently occurring in conventional nutrient deprivation therapy by activating AKT/mTOR pathway phosphorylation. Combination therapy in the xenograft model results in an ≈5-fold increase in therapeutic efficiency as compared with COD treatment alone. This functionally cooperative metabolic coupling strategy holds great promise as a novel polytherapy approach that will benefit patients with solid tumors.

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay.

Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

Highly selective fluorescent probe for detecting mercury ions in water.

Mercury ion (Hg2+) is a well-known toxic heavy metal. It has become one of the most significant environmental pollutants in the world because of its serious physiological toxicity, persistence, easy migration, and high bioconcentration. Thus, the development of methods for monitoring Hg2+ is indispensable. Herein, we have designed and synthesized a new fluorescent probe, TPH, for the detection of Hg2+ in the water environment. The TPH probe could quantitatively detect Hg2+ between 0 and 5 µM (LOD = 16 nM), with a linear range of 0-2.5 µM. In addition, the TPH probe was used to monitor Hg2+ in water samples successfully. Thus, this probe is suitable for monitoring Hg2+ in the actual water environment.

A pipeline for sample tagging of whole genome bisulfite sequencing data using genotypes of whole genome sequencing.

BACKGROUND: In large-scale high-throughput sequencing projects and biobank construction, sample tagging is essential to prevent sample mix-ups. Despite the availability of fingerprint panels for DNA data, little research has been conducted on sample tagging of whole genome bisulfite sequencing (WGBS) data. This study aims to construct a pipeline and identify applicable fingerprint panels to address this problem. RESULTS: Using autosome-wide A/T polymorphic single nucleotide variants (SNVs) obtained from whole genome sequencing (WGS) and WGBS of individuals from the Third China National Stroke Registry, we designed a fingerprint panel and constructed an optimized pipeline for tagging WGBS data. This pipeline used Bis-SNP to call genotypes from the WGBS data, and optimized genotype comparison by eliminating wildtype homozygous and missing genotypes, and retaining variants with identical genomic coordinates and reference/alternative alleles. WGS-based and WGBS-based genotypes called from identical or different samples were extensively compared using hap.py. In the first batch of 94 samples, the genotype consistency rates were between 71.01%-84.23% and 51.43%-60.50% for the matched and mismatched WGS and WGBS data using the autosome-wide A/T polymorphic SNV panel. This capability to tag WGBS data was validated among the second batch of 240 samples, with genotype consistency rates ranging from 70.61%-84.65% to 49.58%-61.42% for the matched and mismatched data, respectively. We also determined that the number of genetic variants required to correctly tag WGBS data was on the order of thousands through testing six fingerprint panels with different orders for the number of variants. Additionally, we affirmed this result with two self-designed panels of 1351 and 1278 SNVs, respectively. Furthermore, this study confirmed that using the number of genetic variants with identical coordinates and ref/alt alleles, or identical genotypes could not correctly tag WGBS data. CONCLUSION: This study proposed an optimized pipeline, applicable fingerprint panels, and a lower boundary for the number of fingerprint genetic variants needed for correct sample tagging of WGBS data, which are valuable for tagging WGBS data and integrating multi-omics data for biobanks.

Insights into the antibacterial mechanism of iron doped carbon dots.

Antibacterial nanomaterials provide promising alternative strategies to combat the bacterial infection due to deteriorating resistance. However, few have been practically applied due to the lack of clear antibacterial mechanisms. In this work, we selected good-biocompatibility iron-doped CDs (Fe-CDs) with antibacterial activity as a comprehensive research model to systematically reveal the intrinsic antibacterial mechanism. Through energy dispersive spectroscopy (EDS) mapping of in situ ultrathin sections of bacteria, we found that a large amount of iron was accumulated inside the bacteria treated with Fe-CDs. Then, combining the data of cell level and transcriptomics, it can be elucidated that Fe-CDs could interact with cell membranes, enter bacterial cells through iron transport and infiltration, increase intracellular iron levels, trigger increased reactive oxygen species (ROS), and lead to disruption of Glutathione (GSH)-dependent antioxidant mechanisms. Excessive ROS further leads to lipid peroxidation and DNA damage in cells, lipid peroxidation destroys the integrity of the cell membrane, and finally leads to the leakage of intracellular substances resulting in bacterial growth inhibition and death. This result provides important insights into the antibacterial mechanism of Fe-CDs and further provides a basis for the deep application of nanomaterials in biomedicine.

Primary Amine Functionalized Carbon Dots for Dead and Alive Bacterial Imaging.

Small molecular dyes are commonly used for bacterial imaging, but they still meet a bottleneck of biological toxicity and fluorescence photobleaching. Carbon dots have shown high potential for bio-imaging due to their low cost and negligible toxicity and anti-photobleaching. However, there is still large space to enhance the quantum yield of the carbon quantum dots and to clarify their mechanisms of bacterial imaging. Using carbon dots for dyeing alive bacteria is difficult because of the thick density and complicated structure of bacterial cell walls. In this work, both dead or alive bacterial cell imaging can be achieved using the primary amine functionalized carbon dots based on their small size, excellent quantum yield and primary amine functional groups. Four types of carbon quantum dots were prepared and estimated for the bacterial imaging. It was found that the spermine as one of precursors can obviously enhance the quantum yield of carbon dots, which showed a high quantum yield of 66.46% and high fluorescence bleaching-resistance (70% can be maintained upon 3-h-irradiation). Furthermore, a mild modifying method was employed to bound ethylenediamine on the surface of the spermine-carbon dots, which is favorable for staining not only the dead bacterial cells but also the alive ones. Investigations of physical structure and chemical groups indicated the existence of primary amine groups on the surface of spermine-carbon quantum dots (which own a much higher quantum yield) which can stain alive bacterial cells visibly. The imaging mechanism was studied in detail, which provides a preliminary reference for exploring efficient and environment-friendly carbon dots for bacterial imaging.

Electrogenerated copper selenide with positive charge to efficiently capture and combat drug-resistant bacteria for wound healing.

Limited by the effective radius of metal ion release, higher concentrations of antibacterial agents are usually required to achieve satisfactory efficacy. Unfortunately, the potential cytotoxicity of metal ions limits the administered dose, which greatly hinders the widespread use of metal antibacterial agents. In this work, we used a convenient electrochemical method to prepare electropositive copper selenide (CuSe) nanosheets gathered from the cathode. Under physiological conditions, trace amounts of electrolytic CuSe (E-CuSe, 1 µg mL-1) could electrostatically bind to bacterial membranes and almost completely kill three resistant bacteria models (106 colony forming unit (CFU) mL-1). The extremely low effective dose of E-CuSe reaches a new benchmark in comparison with copper-based nanomaterials in other related studies. In addition, due to the reasonable coupling of selenium and copper, the as-prepared E-CuSe nanosheets exhibit lower cytotoxicity compared to copper oxide. As expected, the E-CuSe performed well in resistant bacteria-infected wound healing in rats, rapidly promoting wound tissue with a diameter of about 1 cm recovery within 7 days. Transcriptome analysis revealed the E-CuSe mainly acted on the membrane transport and DNA synthesis systems of bacterial cells. This work presents an efficient and in-depth paradigm for the scientific design and inactivation mechanism of metal antibacterial agents.

Array Study of VLF Thin-Film Magnetoelectric Antenna with a Microbridge Structure.

Recently, magnetoelectric (ME) antennas have become a hot topic in the field of antenna miniaturization in the very-low-frequency (VLF) band because their size can be reduced to one-ten-thousandth of the size of conventional electric antennas. However, they still suffer from narrow transmission/reception bandwidth and weak radiation intensity. To address these issues, VLF thin-film ME antennas with a microbridge structure are designed, and the method of array connection is used. Test results show that the detection limit of the ME antenna unit is 636 pT/√Hz at 23 kHz and the radiant magnetic field intensity at 0.12 m is 0.87 nT (input power of 10 mW). By series-connecting three ME antenna units with the same resonance frequency, the output response has been increased to 1.72 times and the EM wave radiation intensity is increased to 1.9 times compared to a single unit. By parallel-connecting two ME antenna units with different resonance frequencies, the output response bandwidth has been expanded to 1.56 times compared to a single unit, and the signal radiation bandwidth has been expanded to 1.47 times. This work provides a valuable reference for the future larger-scale arraying of ME antennas.

Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Real-World Study Based on the US FDA Adverse Event Reporting System Database.

BACKGROUND AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used as adjunctive therapy to lifestyle intervention and metformin treatment in type 2 diabetes mellitus patients, as most GLP-1RAs have cardiovascular benefits; however, a number of adverse events (AEs) have been reported in postmarketing surveillance. OBJECTIVE: The aim of this study was to describe the AEs associated with GLP-1RA monotherapy and identify important medical event (IME) signals for GLP-1RAs. METHODS: Data from 1 April 2005 to 31 December 2021 from the US FDA Adverse Event Reporting System (FAERS) database were extracted to conduct disproportionality analysis and Bayesian analysis. AEs and IMEs were classified by system organ classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The reporting odds ratio (ROR) and information component (IC) were used to indicate the disproportionality. RESULTS: A total of 71,515 records involving GLP-1RA monotherapy were submitted to the database, of which 16,350 records were GLP-1RA/IME pairs. Significant disproportionality emerged in five SOCs: 'gastrointestinal disorders' (n = 13,104; lower end of the 95% confidence interval (CI) of the IC [IC025] = 1.34), 'investigations' (n = 6889; IC025 = 0.64), 'metabolism and nutrition disorders' (n = 2943; IC025 = 0.44), 'neoplasms benign/malignant' (n = 1989; IC025 = 0.01), and 'hepatobiliary disorders' (n = 1497; IC025 = 0.38). The most common AEs were pancreatitis, nausea, and weight decrease. Unexpected significant AEs were detected, such as ileus, osteomyelitis, renal cell carcinoma, nephrolithiasis, and drug-induced liver injury. CONCLUSION: The majority of AEs have been listed in the prescribing information or reported in previous studies, however we found significant disproportionality in some specific tumor- and liver-related AEs. Clinicians should pay more attention to the newly detected disproportionality that may be triggered by GLP-1RAs, especially in the vulnerable population after long-term use. Considering the limitations of the FAERS database, there is a need for additional pharmacoepidemiological approaches to validate the results of this study.

Hybridization chain reaction-mediated Fe2MoO4 bimetallic nanozyme for colorimetric risk prediction of bladder cancer.

The high morbidity and mortality of bladder cancer highlights the need of cancer risk prediction, which can be achieved by the analysis of the related DNA mutations. The facile, low-cost colorimetric methods were promising but still suffered from low sensitivity or poor selectivity. Therefore, highly active colorimetric probes and DNA/signal amplification technologies are still in urgent need to be explored. Herein, a bimetallic nanozyme Fe2MoO4 NPs with excellent peroxidase-like activity were successfully synthesized as the colorimetric probe, combining with hybridization chain reaction (HCR) to analyze the PSCA rs2294008 (C > T) as a factor for risk prediction of bladder cancer. The absorbance variation and selectivity can then be amplified upon the HCR, which could lead to prolonged DNA length beyond the range of •OH action and double chain with more negative charge to occupy more TMB while repelling the negatively charged nanozyme. Under the optimized conditions, the as-proposed method can achieve sensitive detection of the DNA mutation in the concentration range of 25 pM to 4 nM and detection limit as low as 2 pM, which is superior or comparable to most previously reported colorimetric sensors. Moreover, the practicability of the sensor was verified via the application in serum samples, showing satisfactory accuracy and good reproducibility.

A novel highly specific colorimetric fluorescent probe for the detection of nitrite in aqueous solution.

Developing an effective method for the detection of nitrite (NO2 - ) ions in the natural environment especially in environmental waters and soils is very necessary, since they will cause serious damage to human health once excess NO2 - ions enters the human body. Therefore, a new colorimetric fluorescent probe NB-NO2 - for determining NO2 - ions was designed, which possesses good water-solubility and satisfactory selectivity over other common ions for NO2 - ions. The addition of NO2 - ions changed the color of solution from blue to colorless seen by the naked-eye. Furthermore, through test and calculation, the detection limit of the probe NB-NO2 - is 129 nM. Based on the earlier excellent characteristics, the probe NB-NO2 - was successfully used for monitoring NO2 - ions in environmental waters and soils.

Evaluation of single and joint toxicity of perfluorooctanoic acid and arsenite to earthworm (Eisenia fetida): A multi-biomarker approach.

Perfluorooctanoic acid (PFOA) and arsenic are ubiquitous environmental contaminants and could co-exist in soil. However, data on their possible combined toxic effects on terrestrial organisms are still lacking. In this study, we exposed earthworm Eisenia fetida to artificial soil spiked with different sub-lethal levels of PFOA, arsenite (As(III)) or their mixture for 28 days. The bioaccumulation and multi-biomarker responses in the earthworms were measured. Results showed that the co-existence of PFOA and As(III) in soil enhanced the bioaccumulation of arsenic while reduced the bioaccumulation of PFOA. Most selected biomarkers exhibited significant responses at higher exposure levels and indicated oxidative damages. Biomarker Response Index (BRI) was used to integrate the multi-biomarker responses and the results showed significant dose-effect relationships between biological health status and exposure levels. Moreover, variation analysis of multi-biomarkers and BRI proved that As(III) exhibited more toxicity than PFOA to the earthworms. Based on BRI results, Effect Addition Index (EAI) was calculated to evaluate the joint effects of the two toxicants. According to EAI, the joint toxicity of PFOA and As(III) was related to exposure concentration, changing from synergism to slight antagonism with the increase of exposure level. These results provide valuable toxicological information for the risk assessment of co-exposure to PFOA and arsenic in the soil environment. Moreover, this study proved that BRI is an effective tool to integrate multi-biomarker responses, and its combination with EAI provides a useful combined approach to evaluate the joint effects of mixed contamination systems.