High-performance presurgical differentiation of glioblastoma and metastasis by means of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics.

OBJECTIVES: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM). MATERIALS AND METHODS: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison. RESULTS: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar. CONCLUSION: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM. CLINICAL RELEVANCE STATEMENT: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity. KEY POINTS: • The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. • Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. • The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model.

Nine dietary habits and risk of colorectal cancer: a Mendelian randomization study.

BACKGROUND: Epidemiological studies have provided evidence that there is an association between diet and colorectal cancer. However, the causal relationship between dietary habits and colorectal cancer remains unknown. METHODS: The UK Biobank provided summary-level genome-wide association study data for nine dietary habits, including alcohol consumption (n = 549,703), instant coffee consumption (n = 250,308), fruit consumption (n = 210,947), meat consumption (n = 210,947), full cream milk consumption (n = 41,306), sweets consumption (n = 25,521), tea consumption (n = 501,494), vegetable consumption (n = 210,947), and yogurt/ice cream consumption (n = 210,947). Additionally, data on colorectal cancer were collected, consisting of 5,567 cases and 372,016 controls. The MR analysis employed inverse variance weighted, weighted median, MR-Egger regression, and MR multivariate residuals tests. RESULTS: In the predominantly European population, a positive association was observed between vegetables (OR = 1.014, 95% CI = 1.000-1.029, p = 0.048) and an increased risk of colorectal cancer. The results for vegetable did not survive correction for multiple comparisons. However, no strong evidence was found for other dietary factors, such as alcohol (OR = 1.012, 95% CI = 0.974-1.051, p = 0.556), fruit (OR = 1.007, 95% CI = 0.986-1.029, p = 0.512), meat (OR = 1.000, 95% CI = 0.987-1.026, p = 0.968), full cream milk (OR = 1.019, 95% CI = 0.979-1.061, p = 0.357), sweets (OR = 0.998, 95% CI = 0.991-1.004, p = 0.524), and tea (OR = 1.002, 95% CI = 0.994-1.009, p = 0.672), with regards to colorectal cancer risk in the European population. CONCLUSIONS: Our study highlights the need for a more nuanced approach to dietary recommendations for CRC prevention, with greater emphasis adherence to the Mediterranean dietary pattern.

Association of sleep duration and risk of mental disorder: a systematic review and meta-analysis.

BACKGROUND: The effects of sleep duration on the development of mental illness remain controversial. Therefore, it is necessary to identify the effects of long or short sleep duration on psychological disorders, which could reveal new ways for preventing and treating mental health conditions cheaply. METHODS: Identifying published papers was accomplished by using the following five English databases on March 16, 2022: PubMed, MEDLINE, Embase, Web of Science databases, and Scopus. Cross-sectional and cohort studies were considered if they evaluated the association of sleep duration with all kinds of mental illness in adults. We excluded case reports, editorials, narrative reviews, and studies without detailed information on sleep duration. Summary effect-size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. Mantel-Haenszel's random-effects model was used to estimate the inconsistency index (I2) and Tau2 index (measurement of heterogeneity). RESULTS: A total of 52 studies were included in this analysis, consisting of 14 cohort studies and 38 cross-sectional studies. These studies involved a combined sample size of 1,407,891 participants who met the inclusion criteria. Cohort (adjusted RR = 1.42, 95% CI: 1.26-1.60, P < .001, I2 = 37.6%, Tau2 = 0.014) and cross-sectional studies (adjusted OR = 1.67, 95% CI: 1.57-1.77, P < .001, I2 = 79.7%, Tau2 = 0.060) concluded that short sleep duration increased mental disorder risks. The same conclusions were acquired in the subgroup analysis, especially for depression (adjusted RR = 1.43, 95% CI: 1.24-1.65, P < .001, I2 = 80.4%, Tau2 = 0.082), anxiety (adjusted RR = 1.30, 95% CI: 1.04-1.63, P = .002, I2 = 0.0%, Tau2 = 0.000), and PTSD (adjusted RR = 1.35, 95% CI: 1.04-1.76, P = .022, I2 = 24.1%, Tau2 = 0.013) in cohort studies. The results of subgroup analysis indicated that long sleep duration was not a risk factor for depression (adjusted RR = 1.15, 95% CI: 0.98-1.34, P = .088, I2 = 63.4%, Tau2 = 0.045) and anxiety (adjusted RR = 1.37, 95% CI: 0.93-2.03, P = .114, I2 = 0.0%, Tau2 = 0.000). CONCLUSIONS: Short sleep duration, not long sleep duration, is an independent predictor of developing mental disorders, particularly anxiety and depression.

Radiomic texture analysis based on neurite orientation dispersion and density imaging to differentiate glioblastoma from solitary brain metastasis.

BACKGROUND: We created discriminative models of different regions of interest (ROIs) using radiomic texture features of neurite orientation dispersion and density imaging (NODDI) and evaluated the feasibility of each model in differentiating glioblastoma multiforme (GBM) from solitary brain metastasis (SBM). METHODS: We conducted a retrospective study of 204 patients with GBM (n = 146) or SBM (n = 58). Radiomic texture features were extracted from five ROIs based on three metric maps (intracellular volume fraction, orientation dispersion index, and isotropic volume fraction of NODDI), including necrosis, solid tumors, peritumoral edema, tumor bulk volume (TBV), and abnormal bulk volume. Four feature selection methods and eight classifiers were used for the radiomic texture feature selection and model construction. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the models. Routine magnetic resonance imaging (MRI) radiomic texture feature models generated in the same manner were used for the horizontal comparison. RESULTS: NODDI-radiomic texture analysis based on TBV subregions exhibited the highest accuracy (although nonsignificant) in differentiating GBM from SBM, with area under the ROC curve (AUC) values of 0.918 and 0.882 in the training and test datasets, respectively, compared to necrosis (AUCtraining:0.845, AUCtest:0.714), solid tumor (AUCtraining:0.852, AUCtest:0.821), peritumoral edema (AUCtraining:0.817, AUCtest:0.762), and ABV (AUCtraining:0.834, AUCtest:0.779). The performance of the five ROI radiomic texture models in routine MRI was inferior to that of the NODDI-radiomic texture model. CONCLUSION: Preoperative NODDI-radiomic texture analysis based on TBV subregions shows great potential for distinguishing GBM from SBM.

Direct access to carbamates via acylation of arylamines with dialkyl azodicarboxylates under metal-free conditions.

A novel C-N coupling of various arylamines with dialkyl azodicarboxylates under metal-free conditions for the rapid assembly of carbamates has been achieved. This established protocol features mild reaction conditions, simple operation, broad substrate scope, moderate to excellent yields and good tolerance of functional groups. Moreover, the potential synthetic utility of products was exemplified by a series of intriguing chemical operations.

The Effects of a Healthy Diet on Asthma and Wheezing in Children and Adolescents: A Systematic Review and Meta-Analysis.

Background: Asthma is a public health problem requiring focused attention. This study aimed to systematically evaluate the association between dietary structure and asthma or wheezing in children. Methods: The study protocol of this meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration code CRD42023390191. A total of 8397 articles were retrieved, searching PubMed, Medline, Embase, Web of Science, and Scopus databases as of November 21, 2022. Two independent authors were responsible for independently conducting the literature screening process. Effect-size estimates were expressed as odds ratio (OR) in cross-sectional studies and risk ratio (RR) in cohort studies with a 95% confidence interval (CI). Summary effect estimates were evaluated with random-effect models. Meanwhile, subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Results: A total of 65 studies, including 567,426 subjects had been analyzed. Overall analyses of cross-sectional studies revealed that a healthy diet was protective against asthma (adjusted OR=0.85, 95% CI: 0.80-0.89, P <0.001, I2=69.8%, Tau2=0.026) and wheezing (adjusted OR=0.85, 95% CI: 0.81-0.89, P <0.001, I2=66.8%, Tau2=0.015) in children and adolescents. Conversely, unhealthy diets can exacerbate asthma (adjusted OR=1.28, 95% CI: 1.20-1.36, P <0.001, I2=64.9%, Tau2=0.019) and wheeze (adjusted OR=1.09, 95% CI: 1.02-1.16, P =0.006, I2=75.2%, Tau2=0.023) in children and adolescents. The same trend was found in cohort studies (adjusted RR=0.72, 95% CI: 0.58-0.90, P =0.003, I2=83.5%, Tau2=0.105). A clear trend was observed between high-frequency healthy diets (OR=0.80; 95% CI: 0.71-0.89; P <0.001) is more protective against asthma than low-frequency healthy diets (OR=0.81; 95% CI: 0.70-0.94; P =0.007). Conclusion: Our findings highlight the protective effects of a healthy diet on asthma and wheezing in children, including fruit, seafood, cereals, and the Mediterranean diet.

Ecological effect life cycle assessment of house buildings based on emergy footprint model.

Construction is an important sector for climate action. The construction, operation and maintenance, demolition and disposal stages of house buildings consume many resources and have a significant impact on society, the economy and the environment. To assess such efforts, we propose the emergy footprint model of house buildings, which can quantitatively analyse the ecological effect in the house buildings life cycle. The research shows the following. China's ecological efficiency of the housing sector is characterized by improvement. In the house building fifty-year life cycle, the emergy footprint of the operation and maintenance stage is the largest (75.92%), followed by the construction stage (21.95%), but the emergy footprint intensity of the latter is 4.82 times that of the former. Reducing energy consumption and carbon dioxide emissions in the operation and maintenance stage is the key to reducing the life cycle emergy footprint of house buildings. The ecological impact coefficient of house buildings is negatively exponentially correlated with their service life. It reaches ecological break-even when the service period of the house building is equal to 36.73 years. If the house building is demolished after less than nine years of service, the impact is extremely unfavourable.

An edge-based approach for virtual network embedding based on the graph edit distance.

Virtualization and resource isolation techniques have enabled the efficient sharing of networked resources. How to control network resource allocation accurately and flexibly has gradually become a research hotspot due to the growth in user demands. Therefore, this paper presents a new edge-based virtual network embedding approach to studying this problem that employs a graph edit distance method to accurately control resource usage. In particular, to manage network resources efficiently, we restrict the use conditions of network resources and restrict the structure based on common substructure isomorphism and an improved spider monkey optimization algorithm is employed to prune redundant information from the substrate network. Experimental results showed that the proposed method achieves better performance than existing algorithms in terms of resource management capacity, including energy savings and the revenue-cost ratio.

A high-sensitivity single-light-source triaxial atomic magnetometer with double-cell and orthogonally pumped structure.

We first report a single-light-source orthogonally pumped triaxial atomic magnetometer with a double-cell structure. By using a beam splitter to equally allocate the pump beam, the proposed triaxial atomic magnetometer is responsive to magnetic fields in all three directions, and without sacrificing system sensitivity. The experimental results indicate that, the magnetometer achieves a sensitivity of 22 fT/Hz1/2 in x-direction with a 3-dB bandwidth of 22 Hz, a sensitivity of 23 fT/Hz1/2 in y-direction with a 3-dB bandwidth of 23 Hz, and a sensitivity of 21 fT/Hz1/2 in z-direction with a 3-dB bandwidth of 25 Hz. This magnetometer is useful for the applications that require the measurements of the three components of the magnetic field.

Chlorine substitution-dependent toxicities of polychlorinated biphenyls to the earthworm Eisenia fetida in soil.

Polychlorinated biphenyls (PCBs) with different chlorine substitution patterns often coexist in e-waste-processing sites. However, the single and combined toxicity of PCBs to soil organisms and the influence of chlorine substitution patterns remain largely unknown. Herein, we evaluated the distinct in vivo toxicity of PCB28 (a trichlorinated PCB), PCB52 (a tetrachlorinated PCB), PCB101 (a pentachlorinated PCB), and their mixture to earthworm Eisenia fetida in soil, and looked into the underlining mechanisms in an in vitro test using coelomocytes. After a 28-days exposure, all PCBs (up to 10 mg/kg) were not fatal to earthworms, but could induce intestinal histopathological changes and microbial community alterations in the drilosphere system, along with a significant weight loss. Notably, pentachlorinated PCBs with a low bioaccumulation ability showed greater inhibitory effects on the growth of earthworm than lowly chlorinated PCBs, suggesting that bioaccumulation was not the main determinant of chlorine substitution-dependent toxicity. Furthermore, in vitro assays showed that the highly chlorinated PCBs induced a high-percentage apoptosis of eleocytes in the coelomocytes and significantly activated antioxidant enzymes, indicating that the distinct cellular vulnerability to lowly/highly chlorinated PCBs was the main contributor to the PCBs toxicity. These findings emphasize the specific advantage of using earthworms in the control of lowly chlorinated PCBs in soil due to their high tolerance and accumulation ability.

Diastereoselective Synthesis of Dihydrobenzofuran-Fused Spiroindolizidines via Double-Dearomative [3 + 2] Cycloadditions.

Spiroindolizidine oxindoles represent a kind of privileged scaffold in many biologically active natural alkaloids. 2,3-Dihydrobenzofuran derivatives exhibit significant bioactivities in a variety of pharmaceuticals. Herein, we assembled these two privileged fragments into a small molecule via double-dearomative [3 + 2] cycloadditions with pyridinium ylides and 2-nitrobenzofurans. This protocol features remarkable advantages including wide substrate scope, mild condition, high level of diastereoselectivities and yields. Thus, a collection of spiroindolizidine-fused dihydrobenzofurans/indolines were facilely produced efficiently.

Bioresponses of earthworm-microbiota symbionts to polychlorinated biphenyls in the presence of nano zero valent iron in soil.

Both earthworms and nano zero-valent iron (nZVI) have been recently regarded as important approaches for in-situ remediation of polychlorinated biphenyls (PCBs) in soil. However, the combined action of earthworms and nZVI toward PCBs, and the biological responses of earthworm-microbiota symbionts to nZVI-PCBs co-exposure in soil remediation systems remain unclear. In this study, a 28-d exposure with different levels of polychlorinated biphenyls (PCBs) and nZVI was applied to earthworm Eisenia fetida in an agricultural soil. Both physiological responses of earthworms and their surrounding microbiota in gut and soil were examined. Kinetic modelling parameters showed a doubled PCB accumulation in earthworms with the presence of nZVI. Meanwhile, nZVI-PCBs coexposure synergistically stimulated the activities of superoxide dismutase (SOD) and catalase (CAT), along with the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) in earthworms. Based on integrated metabolomic and 16S rRNA analysis, it was found that earthworms provided certain metabolites, e.g., S-(2-hydroxyethyl)glutathione, 16-hydroxypalmitic acid, and formamide, beneficial to PCB-degrading microbiota (Novosphingobium and Achromobacter) in the intestine. Our findings of nZVI-enhanced PCB bioaccumulation and the defense mechanism afforded by the earthworm-microbiota symbionts toward PCB-nZVI exposure show the promise of combining earthworms with nZVI for the remediation of PCBs-contaminated soil.

SARS-CoV-Related Pandemic Outbreaks and Mental Disorder Risk.

ABSTRACT: This study aimed to quantify the association between exposure to pandemic outbreaks and psychological health via a comprehensive meta-analysis. Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates were expressed as odds ratio (OR) with 95% confidence interval (CI). Data from 22 articles, involving 40,900 persons, were meta-analyzed. Overall analyses revealed a significant association of exposing to SARS-CoV-related pandemics with human mental health (OR, 1.32; 95% CI, 1.24-1.40; p < 0.001). Subgroup analyses showed that anxiety (OR, 1.37; 95% CI, 1.19-1.58; p < 0.001), depression (OR, 1.28; 95% CI, 1.15-1.42; p < 0.001), posttraumatic stress (OR, 1.36; 95% CI, 1.17-1.58; p < 0.001), and psychological distress (OR, 1.25; 95% CI, 1.11-1.40; p < 0.001) were all obviously related to pandemic diseases. In the context of infectious disease outbreaks, the mental health of general populations is clearly vulnerable. Therefore, all of us, especially health care workers, need special attention and psychological counseling to overcome pandemic together.

Association Between Recombinant Growth Hormone Therapy and All-Cause Mortality and Cancer Risk in Childhood: Systematic Review and Meta-Analysis.

Objectives: The safety of recombinant human growth hormone (rhGH) treatment in childhood and the role of rhGH therapy in promoting tumorigenesis and progression have been the subject of debate for decades. We aimed to systematically assess the relationship between rhGH therapy in children and adolescents and clinical outcomes, including all-cause mortality, cancer mortality, cancer incidence, and risk of the second neoplasm. Methods: Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as standardized mortality ratios (SMRs), standardized incidence ratio (SIR), and relative risk (RR) with a 95% CI. Results: Data from 24 articles, involving 254,776 persons, were meta-analyzed. Overall analyses revealed the association of rhGH therapy was not statistically significant with all-cause mortality (SMR = 1.28; 95% CI: 0.58-2.84; P = 0.547; I 2 = 99.2%; Tau2 = 2.154) and cancer mortality (SMR = 2.59; 95% CI: 0.55-12.09; P = 0.228; I 2 = 96.7%; Tau2 = 2.361) and also cancer incidence (SIR = 1.54; 95% CI: 0.68-3.47; P = 0.229; I 2 = 97.5%; Tau2 = 2.287), yet statistical significance was observed for second neoplasm (RR = 1.77; 95% CI: 1.33-2.35; P = 0.001; I 2 = 26.7%; Tau2 = 0.055). Differences in the geographic region, gender, treatment duration, mean rhGH dose, overall rhGH exposure dose, and initial disease accounted for heterogeneity in the subgroup analyses. Conclusion: Our findings indicate that the rhGH therapy is not related to all-cause mortality and cancer mortality and cancer incidence, yet it seems to trigger a second tumor risk. Future prospective studies are needed to confirm our findings and answer the more challenging question regarding the optimal dose of rhGH therapy in children and adolescents.

Meta-analysis: Early Age at Natural Menopause and Risk for All-Cause and Cardiovascular Mortality.

AIMS: The aim of this meta-analysis was to comprehensively evaluate the association of early age at natural menopause with the risk for all-cause and cardiovascular mortality. METHODS: Literature retrieval was done on August 4, 2020. Article selection and data extraction were completed independently and in duplicate. Early age at natural menopause was grouped into premature menopause (<40 years), early menopause (40-44 years), and relatively early menopause (45-49 years). Effect-size estimates are summarized as hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI). RESULTS: Sixteen articles involving 321,233 women were meta-analyzed. Overall analyses revealed a statistically significant association of early age at natural menopause with all-cause mortality risk (HRadjusted = 1.08, 95% CI: 1.03 to 1.14, P = 0.002; RRadjusted = 1.05, 95% CI 1.01 to 1.08, P = 0.005), but not with cardiovascular mortality risk. In dose-response analyses, the association with all-cause mortality was significant for premature menopause with (HRadjusted = 1.10; 95% CI: 1.01 to 1.21; P = 0.034) and without (RRadjusted = 1.34; 95% CI: 1.08 to 1.66; P = 0.007) considering follow-up intervals. As for cardiovascular mortality, marginal significance was noted for premature menopause after considering follow-up intervals (HR = 1.09; 95% CI: 1.00-1.19; P = 0.045). Subgroup analyses indicated that gender, country, and follow-up periods were possible causes of heterogeneity. There was an overall low probability of publication bias. CONCLUSIONS: Our findings indicate that premature menopause is a promising independent risk factor for both all-cause and cardiovascular mortality.

Sleep duration and obesity in children and adolescents: evidence from an updated and dose-response meta-analysis.

BACKGROUND AND OBJECTIVES: The association between sleep duration and obesity in children and adolescents has been widely evaluated, whereas the current findings are mixed and prospective studies are limited. To shed more light on this issue and explore the dose-response relationship, we performed the present updated meta-analysis by synthesizing the results of prospective cohorts. METHODS: Literature retrieval, study selection and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as relative risk (RR) with 95% confidence interval (CI) or standardized regression coefficient (ß) with standard error. RESULTS: Data from 33 articles, involving 57,848 children and adolescents, were meta-analyzed. Overall analyses revealed statistically significant associations of short (adjusted RR = 1.57, 95% CI: 1.36 to 1.81, P < 0.001) and long sleep duration (0.83, 0.75 to 0.93, 0.001) with obesity. Short sleep duration was also associated with significant changes in body mass index z-score (mean difference = -0.06; 95% CI: -0.09 to -0.04; P < 0.001). By contrast, long sleep duration was identified as a protective factor for childhood obesity. In dose-response analyses, short sleep duration was significantly associated with obesity in toddlers (1-2 years) (adjusted RR = 1.20, 95% CI: 1.07 to 1.34, P = 0.001), preschool-aged (3-5 years) children (1.58, 1.36 to 1.83, <0.001), and school-aged (6-13 years) children (1.82, 1.51 to 2.21, <0.001). In subgroup analyses, geographic region, sleep duration assessment, age, and follow-up interval were possible sources of heterogeneity. CONCLUSIONS: Our findings indicate that short sleep duration can increase the risk of obesity in children and adolescents, especially within 3-13 years of age, and long sleep duration seemed beneficial in preventing obesity.

Combined toxic effects of dioxin-like PCB77 with Fe-based nanoparticles in earthworm Eisenia fetida.

Iron-based nanomaterials hold promise for in situ remediation of persistent halogenated contaminants such as dioxin-like polychlorinated biphenyls, however, their complex interactions and joint toxicity toward beneficial soil biological functions remain unknown. This study examined the effects of nano-zero valent iron (nZVI) on the physiological and morphological changes, on the bioaccumulation of co-existed dioxin-like 3,3',4,4'-tetrachloro-biphenyls (PCB77), and the joint toxicity of nZVI and PCB77 in earthworms Eisenia fetida. An orthogonally designed experiment was conducted through the exposure of E. fetida to the combined and separate nZVI and PCB77 at various concentrations in soil for 28 days (nZVI at the levels of g-Fe/kg-soil and PCB77 at the levels of mg-PCB/kg-soil). Results indicated that both nZVI and PCB77 inhibited the growth and reproduction of earthworms, and the combined exposure resulted in a synergistic effect. The addition of 10 g/kg nZVI decreased the contents of PCB77 and significantly increased the accumulation of PCB77 to a level ranging 14-97 mg/kg in earthworms in a nZVI dose dependent manner. The observed synergism might relate to the aggravated damage of earthworm epidermis in the presence of nZVI. PCB77 and nZVI at their corresponding high levels (10 mg/kg and 10 g/kg) induced oxidative stress and lipid peroxidation in the earthworms through the increased levels of reactive oxygen species and the subsequent inhibition of antioxidant enzymes including superoxide dismutase and catalase. Further metabolomics analyses revealed that the normal glutamic acid metabolism and tricarboxylic acid cycle were disturbed in earthworms exposed to the combined treatment of 10 mg/kg PCB77 and 10 g/kg nZVI. Our findings suggested that earthworms as a sentinel species could be readily employed in toxicity and tolerance studies to succeed the safe applications of nZVI and interestingly earthworms themselves also hold promise for vermiremediation owing to the high bioaccumulation potential of PCBs from contaminated soils.