FGF18 encoding circular mRNA-LNP based on glycerolipid engineering of mesenchymal stem cells for efficient amelioration of osteoarthritis.

Mesenchymal stem cells (MSCs) exhibit substantial potential for osteoarthritis (OA) therapy through cartilage regeneration, yet the realization of optimal therapeutic outcomes is hampered by their limited intrinsic reparative capacities. Herein, MSCs are engineered with circular mRNA (cmRNA) encoding fibroblast growth factor 18 (FGF18) encapsulated within lipid nanoparticles (LNP) derived from a glycerolipid to facilitate OA healing. A proprietary biodegradable and ionizable glycerolipid, TG6A, with branched tails and five ester bonds, forms LNP exhibiting above 9-fold and 41-fold higher EGFP protein expression in MSCs than commercial LNP from DLin-MC3-DMA and ALC-0315, respectively. The introduction of FGF18 not only augmented the proliferative capacity of MSCs but also upregulated the expression of chondrogenic genes and glycosaminoglycan (GAG) content. Additionally, FGF18 enhanced the production of proteoglycans and type II collagen in chondrocyte pellet cultures in a three-dimensional culture. In an OA rat model, transplantation with FGF18-engineered MSCs remarkably preserved cartilage integrity and facilitated functional repair of cartilage lesions, as evidenced by thicker cartilage layers, reduced histopathological scores, maintenance of zone structure, and incremental type II collagen and extracellular matrix (ECM) deposition. Taken together, our findings suggest that TG6A-based LNP loading with cmRNA for engineering MSCs present an innovative strategy to overcome the current limitations in OA treatment.

Small intestinal angiosarcoma on clinical presentation, diagnosis, management and prognosis: A case report and review of the literature.

BACKGROUND: Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues. Small-intestinal angiosarcomas are rare, and the prognosis is poor. CASE SUMMARY: We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma. Small intestinal angiosarcoma is more common in elderly and male patients. Gastrointestinal bleeding, anemia, abdominal pain, weakness, and weight loss were the common symptoms. CD31, CD34, factor VIII-related antigen, ETS-related gene, friend leukemia integration 1, and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma. Small-intestinal angiosarcoma most commonly occurs in the jejunum, followed by the ileum and duodenum. Radiation and toxicant exposure are risk factors for angiosarcoma. After a definite diagnosis, the mean and median survival time was 8 mo and 3 mo, respectively. Kaplan-Meier survival analysis showed that age, infiltration depth, chemotherapy, and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma. Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis. CONCLUSION: Angiosarcoma should be considered for unexplained melena and abdominal pain, especially in older men and patients with a history of radiation exposure. Prompt treatment, including surgery and adjuvant chemotherapy, is essential to prolonging patient survival.

Identification of N7-methylguanosine-related IncRNA signature as a potential predictive biomarker for colon adenocarcinoma.

N7-Methylguanosine (m7G) is an RNA modification serving as a key part of colon cancer development. Thus, a comprehensive analysis was executed to explore prognostic roles and associations with the immune status of the m7G-related lncRNA (m7G-RNAs) in colon adenocarcinoma (COAD). Identification of m7G-RNAs was achieved via Pearson's correlation analysis of lncRNAs in the TCGA-COAD dataset and m7G regulators. A prognostic signature was developed via LASSO analyses. ESTIMATE, CIBERSORT, and ssGSEA algorithms were utilized to assess immune infiltration between different risk groups. Survival analysis suggested the high-risk group possesses poor outcomes compared with the low-risk group. According to the ROC curves, the m7G-RNAs signature exhibited a reliable capability of prediction (AUCs at 1, 3, and 5 years were 0.770, 0.766, and 0.849, respectively). Multivariate hazard analysis proved that the signature was an independent predictive indicator for OS. Moreover, the risk score was related to infiltration levels of naïve B cells, CD4+ memory T cells, and resting NK cells. The result revealed the prognostic value of m7G modification in COAD and provided a novel perspective on personalized immunotherapy strategies.

Effect of Polishing on Lead and Cadmium Bioavailability in Rice and Its Health Implications.

Rice polishing is an important approach to reducing the concentrations of heavy metals in rice, but knowledge of its effect on the Pb and Cd bioavailability in produced rice and the related health risk remains limited. In this study, the effects of rice polishing on the bioaccessibility (BAC) and bioavailability (RBA) of Pb and Cd in rice are assessed using an in vitro method and an in vivo mouse bioassay. The Pb removal rate in brown rice (40%), lightly processed brown rice (62%), germinated rice (74%), and polished rice (79%) gradually enhanced with an increase in the polishing degree, while Cd was difficult to remove by polishing. The Pb and Cd BAC in germinated rice was the highest, while that in brown rice was the lowest. The polished rice Pb and Cd RBA in the liver and kidneys were significantly higher than those in the brown rice group. The Pb RBA in the livers and kidneys in the polished rice group was 26.6% ± 1.68% and 65.3% ± 0.83%, respectively, which was 1.6- and 2.6-times higher than that in the brown rice group, respectively. The Cd RBA values in both the livers and kidneys of the polished rice group were 1.3-times higher than those in the brown rice group. Although polishing reduced the total Pb in the polished rice, it was not enough to offset the increase in bioavailability, and its consumption risk was not weakened. This study highlighted the value of the oral-bioavailability-corrected health risk assessment for assessing the influence of rice polishing on Pb and Cd exposure via rice consumption.

Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice.

SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.

Correlation Between IVIM-DWI Parameters and Pathological Classification of Idiopathic Orbital Inflammatory Pseudotumors: A Preliminary Study.

Objective: To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs). Methods: Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant. Results: Among the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05). Conclusion: The D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP.

SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.

Development and validation of an MRI-based nomogram for the preoperative prediction of tumor mutational burden in lower-grade gliomas.

Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors. In this study, we aimed to determine the value of magnetic resonance (MR)-based preoperative nomogram in predicting TMB status in lower-grade glioma (LGG) patients. Methods: Overall survival (OS) data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by using the Kaplan-Meier method and time-dependent receiver operating characteristic (tdROC) analysis. The magnetic resonance imaging (MRI) data of 168 subjects obtained from The Cancer Imaging Archive (TCIA) were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analyses. Finally, we performed tenfold cross validation. TMB values were retrieved from the supplementary information of a previously published article. Results: The high TMB subtype was associated with the shortest median OS (high vs. low: 50.9 vs. 95.6 months, P<0.05). The tdROC for the high-TMB tumors was 74% (95% CI: 61-86%) for survival at 12 months, and 71% (95% CI: 60-82%) for survival at 24 months. Multivariate logistic regression analysis confirmed that three risk factors [extranodular growth: odds ratio (OR): 8.367, 95% CI: 3.153-22.199, P<0.01; length-width ratio ≥ median: OR: 1.947, 95% CI: 1.025-3.697, P<0.05; frontal lobe: OR: 0.455, 95% CI: 0.229-0.903, P<0.05] were significant independent predictors of high-TMB tumors. The nomogram showed good calibration and discrimination. This model had an area under the curve (AUC) of 0.736 (95% CI: 0.655-0.817). Decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. The average accuracy of the tenfold cross validation was 71.6% for high-TMB tumors. Conclusions: Our results indicated that a distinct OS disadvantage was associated with the high TMB group. In addition, extranodular growth, nonfrontal lobe tumors and length-width ratio ≥ median can be conveniently used to facilitate the prediction of high-TMB tumors.

The cadmium decontamination and disposal of the harvested cadmium accumulator Amaranthus hypochondriacus L.

The heavy metal accumulated biomass after phytoremediation needs to be decontaminated before disposal. Liquid extraction is commonly used to remove and recycle toxic heavy metals from contaminated biomass. In this study, we examined the cadmium (Cd) removal efficiency using different chemical reagents (hydrochloric acid, nitric acid, sulfuric acid, and ethylenediaminetetraacetic acid disodium) of the post-harvest Amaranthus hypochondriacus L. biomass. The purifications for the extracted liquids and ecological risk assessments for the extracted residues were also investigated. We have found that 77.8% of Cd in stems and 62.1% of Cd in leaves were removed by 0.25 M HCl after 24 h. In addition, K2CO3, KOH, and 4 Å molecular sieve could remove ≥89.0% of Cd in the extracted liquids. Finally, after we returned the extracted residues to the earthworm-incubated soil, the extracted biomass negatively affected the growth (weight loss ≥ 11.0%) and survival (mortality ≥ 33.3%) of Eisenia fetida. It should be noted that earthworms decreased soil available Cd concentrations from 0.14-0.05 mg kg-1 to 0.11-0.04 mg kg-1 and offset the negative effects of the Cd-contaminated biomass on soil microbes. Overall, given the cost of reagents, the Cd removal efficiency, and the ecological risks of the extracted biomass, using 0.25 M HCl for liquid extraction and K2CO3 for purification should be recommended. This work highlights the potential of liquid extraction for immediately and directly removing the Cd from fresh contaminated accumulator biomass and the resource cycling potential of the extracted liquids and biomass after purification.

Immobilization of Cadmium by Molecular Sieve and Wollastonite Is Soil pH and Organic Matter Dependent.

The excessive cadmium (Cd) concentration in agricultural products has become a major public concern in China in recent years. In this study, two amendments, 4A molecular sieve (MS) and wollastonite (WS), were evaluated for their potential passivation in reducing Cd uptake by amaranth (Amaranthus tricolor L.) in six soils with different properties. Results showed that the responses of amaranth biomass to these amendments were soil-property-dependent. The effects of MS and WS on soil available Cd were in turn dependent on soil and amendment properties. The application of WS and MS at a dose of 660 mg·kg-1 Si produced the optimum effect on inhibiting Cd accumulation in amaranth shoots (36% and 34%, respectively) and did not affect crop yield. This was predominantly attributed to the marked increase in pH and exogenous Ca or Na, which facilitated the adsorption, precipitation, and complexation of Cd in soils. The immobilization effects of WS and MS were dependent on soil properties, where soil organic matter may have played an important role. In conclusion, MS and WS possess great potential for the remediation of Cd-contaminated acidic soils.

Phytoremediation of cadmium contaminated soils by Amaranthus Hypochondriacus L.: The effects of soil properties highlighting cation exchange capacity.

Phytoremediation is a cost-effective method to remedy Cd-contaminated soils. However, it is difficult to predict the performance of a given (hyper)accumulator at different soils due to the divergent plant-soil mutual fitness. Soil properties could be quite influential in determining plant growth and Cd uptake and therefore affect phytoremediation efficiency. To explore the primary soil factors that regulate the efficiency of phytoremediation, a phytoextraction experiment with grain amaranth (Amaranthus Hypochondriacus L.) was conducted in six long-term Cd-contaminated agricultural soils from southern China. The results showed that besides the soil available Cd, the soil cation exchange capacity (CEC) greatly affected plant growth and the amount of total Cd extraction. The deficiency of available Ca and Mg in low CEC soil caused insufficient uptake of Ca and Mg by grain amaranth, which was adverse to plant growth and Cd detoxification. The impaired plant biomass production sharply influenced plant total Cd accumulation, despite the relatively high Cd concentration in plants. While for the grain amaranth grown in soils with higher CEC, the increases in plant Ca and Mg promoted plant photosynthesis and plant tolerance to Cd stress, as indicated by the increase of leaf chlorophyll content and antioxidant enzyme activities, which contributed to the higher plant biomass and phytoremediation efficiency. These findings highlight that maintaining regular plant biomass production is vital to ensure the efficiency of phytoremediation, and low CEC of soil is a substantial barrier that needs to be concerned and further addressed for efficient phytoremediation of Cd-contaminated soils.

Tributyltin impaired spermatogenesis and reproductive behavior in male zebrafish.

Tributyltin (TBT) was reported to affect sexual behavior and gametogenesis in fish. However, the modes of action involved are largely unclear. In order to elucidate the toxicological mechanisms of TBT in reproduction, zebrafish (Danio rerio) males were exposed to TBT at concentrations of 100 and 500 ng/L for 28 days. After exposure, the sperm count of the treated fish was sharply decreased though the testis weight and gonadosomatic index remained unchanged. Moreover, reduced number of spermatogonia and spermatozoa and increased spermatocytes were observed in TBT-treated fish by histological observation and PCNA-immunostaining. Increased number of apoptotic-positive spermatocytes was also present in TBT-treated fish, indicating an enhanced apoptosis in these cells. Consistent to decreased number of spermatogonia, down-regulated expressions of genes responsible for germ cell proliferation (cyclind1 and pcna) were observed in TBT-treated fish. In contrast, TBT elevated the expressions of genes involved in meiotic entry and maintenance (aldhla2, sycp3 and dmc1) while suppressed the mRNA level of gene responsible for terminus of meiotic entry (cyp26a1), in agreement with arrested meiosis and reduced sperm count. Furthermore, TBT significantly elevated the ratios of bax/bcl-2 and tnfrsf1a/tnfrsf1b in testis, which are markers for intrinsic- and extrinsic-apoptotic pathways, consistent with the enhanced TUNEL positive signals in spermatocytes. Moreover, TBT also significantly affected the parameter of reproductive behaviors in treated fish (reflected by decreased frequency of meeting, visits and time spent in spawning area). Consistently, the expressions of genes responsible for the modulation of reproductive behaviors in brain (such as cyp19a1b, kiss2, gnrh3 and ompb) were significantly down-regulated in treated-fish. Interestingly, disrupted reproductive behaviors of untreated female fish were also observed in the present study. The present study indicated that TBT might affect the reproduction of zebrafish male by disrupting the spermatogenesis and reproductive behavior of the fish.

Bioavailability and bioaccessibility of cadmium in contaminated rice by in vivo and in vitro bioassays.

Consumption of rice is a major pathway of cadmium (Cd) exposure to humans with Cd bioavailability from rice being an important determinant of the potential health risk. We conducted both in vitro bioaccessibility (using four methods) and in vivo bioavailability (using a mouse model) of Cd from six rices. The relative bioavailability (RBA) for Cd ranged from 15 to 56%, 18 to 56% and 3.71 to 54% based on kidney, liver and femur, respectively, which was negatively correlated with total Cd concentration in contaminated rice (r2 = 0.74-0.94). Results of cadmium bioaccessibility in rice varied among different assays. When the relationship between the in vitro and in vivo data was assessed, all the correlations between the four in vitro methods and the mouse assay based on the liver or kidney were generally weak (r2 = 0.0006-0.52). Results of in vitro digestion models varied drastically among the different methods, suggesting that there were limitations for the in vitro methods to predict Cd relative bioavailability in contaminated rice. Together with the observation of poor correlations between the in vivo and in vitro results, it is strongly suggested that further exploration and more optimization of in vitro methods are required for use in human health risk assessment.

Use of Dietary Components to Reduce the Bioaccessibility and Bioavailability of Cadmium in Rice.

Reducing Cd bioavailability in the systemic circulation is an alternative strategy to reduce Cd exposure. The influence of 39 dietary components on Cd bioaccessibility in water or rice was determined using an in vitro gastrointestinal model, following which an in vivo bioassay was used to determine the most effective components on Cd bioavailability in rice. The results showed that several components significantly reduced the solubility of Cd (10-98%) in the intestinal phase. Tannic acid, TiO2, zinc gluconate, CaCl2, and proanthocyanidins were the most effective in decreasing Cd bioaccessibility in rice, with reductions of 93-97, 54-61, 32-49, 24-32, and 11-14%, respectively. Upon adding the dietary components, the reduction rates of the Cd-relative bioavailability (Cd-RBA) were 20-58 and 10-31% in the kidneys and the liver, respectively. The results may have important implications for reducing health risks associated with Cd exposure via consumption of rice.

Phylogenetic perspective on the relationships and evolutionary history of the Acipenseriformes.

The Acipenseriformes, as one of the earliest extant vertebrates, plays an important role in the evolution of fishes and even the whole vertebrates. Here we collected and analyzed all complete mitochondrial genomes of Acipenseriformes species. Phylogenetic analyses demonstrated that the polytomous branch included Acipenseridae and Polyodontidae formed five clades. The Polyodontidae clade and the Scaphirhynchus clade both were monophyletic group, whereas the Acipenser species and the Huso species both were polyphyletic group. The Bayesian divergence times showed that the origin time for Acipenseriformes was at 318.0 Mya, which was similar to the some previous results of 312.1 Mya, 346.9 Mya and 389.7 Mya. The result was in good consistent with the paleontological data available and the split time of the Pacific and Atlantic Oceans from the Jurassic to the Cretaceous (Laurasia splits in North America and Eurasia). The dN/dS ratios showed the evolutionary rates gradually slow down in five major Acipenseriformes clades from the Clade A (the Pacific sturgeons species) to Clade C (the genus Scaphirhynchus), which was related to the process of geographical formation.

Apolipoprotein E Peptide-Guided Disulfide-Cross-Linked Micelles for Targeted Delivery of Sorafenib to Hepatocellular Carcinoma.

Sorafenib (SF) is an FDA-approved molecular-targeted drug for treating hepatocellular carcinoma (HCC). SF, however, suffers from poor water solubility, low bioavailability, dose-limiting side effects, and possible drug resistance. Here, we report on apolipoprotein E peptide-decorated disulfide-cross-linked micellar SF (ApoE-Ms-SF) as a targeted and intelligent formulation for HCC therapy. ApoE-Ms-SF was prepared with a good SF loading of 7.0 wt %, small size (37 nm), high stability, and reduction-triggered drug release from poly(ethylene glycol)-b-poly(ε-caprolactone-co-dithiolane trimethylene carbonate)-mefenamate (PEG-P(CL-DTC)-MA) and ApoE-modified ApoE-PEG-P(CL-DTC) block copolymers. MTT assays in low-density lipoprotein receptors (LDLRs) overexpressing SMMC-7721 human liver cancer cells showed ApoE density-dependent antitumor potency of ApoE-Ms-SF, in which 7.5% ApoE led to the best antitumor effect (IC50: 8.5 vs 23.3 µg/mL for free SF). Confocal studies, flow cytometry, western blot, and apoptotic assays illustrated clearly a more efficient uptake of ApoE-Ms than nontargeted Ms by SMMC-7721 cells as well as lower phosphorylated extracellular signal-regulated kinase protein level and better cell apoptosis caused by ApoE-Ms-SF compared with Ms-SF and free SF. ApoE-Ms-SF revealed a long circulation time (elimination half-life = 6.8 h). DiR-loaded ApoE-Ms showed a significantly higher accumulation in SMMC-7721 tumor than the nontargeted counterpart. The therapeutic outcomes in the orthotopic SMMC-7721 tumor models demonstrated that ApoE-Ms-SF reduced SF-associated side effects and brought about enhanced angiogenesis inhibition and tumor apoptosis compared to free SF and Ms-SF controls, leading to a better treatment of HCC.

Phosphate addition diminishes the efficacy of wollastonite in decreasing Cd uptake by rice (Oryza sativa L.) in paddy soil.

Cadmium (Cd) contamination in paddy soils poses food security risks and public health concerns. Exploring effective strategies to reduce rice grain Cd is an urgent need. In this study, field plot experiments were conducted to evaluate the effects of wollastonite application with or without phosphate (P) addition on Cd accumulation in rice (Oryza sativa L.). Co-application of P and wollastonite showed greater efficiency than wollastonite amendments alone in raising soil pH and CEC and decreasing soil Cd availability. Cd concentration in brown rice was decreased by 71% under the wollastonite treatment alone, but was decreased by only 29-39% when wollastonite was coupled with different P amendments. This seeming contradiction could be ascribed to the dramatic decline in the phytoavailability of manganese (Mn) and the increase in molar ratio of iron (Fe) to Mn (Fe/Mn) in Fe plaques on root surfaces in the presence of P additions. Significant negative correlations between Mn and Cd in rice plants and positive correlations between Fe/Mn in Fe plaque and Cd in rice plants indicated that P-induced soil Mn deficiency and reduced Mn in Fe plaque impeded the alleviation of Cd accumulation in rice. Application of wollastonite in Si-deficient paddy soils was effective in reducing rice Cd accumulation while boosting rice yield, but co-application of P and wollastonite was counterproductive and should be avoided. This work emphasized that a better understanding of the relationships between Cd and related mineral nutrient uptake would be helpful in developing more efficient measures to reduce rice grain Cd.

Inhibitory effect of cadmium exposure on digestive activity, antioxidant capacity and immune defense in the intestine of yellow catfish (Pelteobagrus fulvidraco).

Cadmium (Cd) is a toxic heavy metal that can pose a serious threat to aquatic organisms. To evaluate the physiological response and defense mechanism of fish intestine to Cd toxicity, yellow catfish (Pelteobagrus fulvidraco) were exposed to 0 (control), 50 µg/L and 200 µg/L Cd2+ for a period of 8 weeks, and then histological changes, digestive activity, antioxidant status and immune responses in the anterior intestine were assessed. After exposure, significant growth retardation and Cd accumulation were observed, and obvious histopathological lesions in the intestine such as increased goblet cells, excessive mucus, vacuolization and thickened lamina propria were detected. Intestinal digestive enzymes activities and related gene expression were inhibited markedly in Cd2+ treatments. Furthermore, Cd exposure induced oxidative stress inhibiting antioxidant activity, characterized by an increase in malondialdehyde level as well as the decrease in the activity and transcription level of antioxidant enzymes. In addition, exposure to Cd2+ down-regulated the expression of key genes involved in the immune response (lys, c3, tor, tgf-ß, il-10, tnf-α and il-8), suggesting immune defense was inhibited. Taken together, the decreased digestive enzyme activity and Cd-induced toxicity stress for antioxidant and immune systems in the intestine might be account for individual growth retardation.