Reassignment of the Structure of a Tryptophan-Containing Cyclic Tripeptide Produced by the Biarylitide Crosslinking Cytochrome P450blt.

The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450Blt from Micromonospora sp. MW-13 has been reanalysed by a series of NMR, computational and isotope labelling experiments and shown to contain a C-N rather than a C-O bond. Additional in vivo experiments using such a modified peptide show there is a general tolerance of biarylitide crosslinking P450 enzymes for histidine to tryptophan mutations within their minimal peptide substrate sequences despite the lack of such residues noted in natural biarylitide gene clusters. This work further highlights the impressive ability of P450s from biarylitide biosynthesis pathways to act as biocatalysts for the formation of a range of sidechain crosslinked tripeptides.

An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides.

Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.

Organophosphate Level Evaluation for the Poisoning Treatment by Enzyme Activation Regeneration Strategy with Oxime-Functionalized ZIF-8 Nanoparticles.

In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 µg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R2 = 0.9889), and the LOD was 0.073 µg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.

Simple method for visual detection of nitrite using fluorescence and colorimetry by poly (tannic acid) nanoparticles.

The nitration reaction of nitrite and phenolic substances was first used to identify and detect NO2- by taking fluorescent poly (tannic acid) nanoparticles (FPTA NPs) as sensing platform. With the low cost, good biodegradable and convenient water-soluble FPTA NPs, a fluorescent and colorimetric dual modes detecting assay was realized. In fluorescent mode, the linear detection range of NO2- was 0-36 µM, the LOD was as low as 3.03 nM, and the response time was 90 s. In colorimetric mode, the linear detection range of NO2- was 0-46 µM, and the LOD was as low as 27 nM. Besides, a smartphone with FPTA NPs@ agarose hydrogel formed a portable detection platform to test the fluorescent and visible color changes of FPTA NPs for NO2- sensing as well as for accurate visualization and quantitative detection of NO2- in actual water and food samples.

A Chemoenzymatic Approach to Investigate Cytochrome P450 Cross-Linking in Glycopeptide Antibiotic Biosynthesis.

Glycopeptide antibiotics (GPAs) are important and medically relevant peptide natural products. In the context of antimicrobial resistance (AMR), understanding and manipulating GPA biosynthesis is essential to discover new bioactive derivatives of these peptides. Among all the enzymatic steps in GPA biosynthesis, the most complex occurs during the maturation (cross-linking) of the peptide aglycone. This is achieved-while the peptide remains attached to the nonribosomal peptide synthetase (NRPS) machinery-through the action of a cytochrome P450 (CYP450 or Oxy)-mediated cyclization cascade. There is great interest in understanding the formation of the cross-links between the aromatic side chains in GPAs as this process leads to the cup-shaped aglycone, which is itself a requirement for antibiotic activity. In this regard, the use of in vitro experiments is crucial to study this process. To address the process of peptide cyclization during GPA biosynthesis, a series of peptide substrates and different Oxy enzymes are required. In this chapter, we describe a practical and efficient route for the synthesis of peptidyl-CoAs, the expression of proteins/enzymes involved in the in vitro cyclization assay, the loading of the PCP with peptidyl-CoAs, an optimized CYP450-mediated cyclization cascade and assay workup followed by mass spectrometry (MS) characterization. This in vitro assay affords high conversion to cyclic peptides and demonstrates the tolerance of the P450s for novel GPA precursor peptide substrates.

Ultrasensitivity Detecting AChE through "Covalent Assembly" and Signal Amplification Strategic Approaches and Applied to Screen Its Inhibitor.

An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.

Cytochrome P450Blt Enables Versatile Peptide Cyclisation to Generate Histidine- and Tyrosine-Containing Crosslinked Tripeptide Building Blocks.

We report our investigation of the utility of peptide crosslinking cytochrome P450 enzymes from biarylitide biosynthesis to generate a range of cyclic tripeptides from simple synthons. The crosslinked tripeptides produced by this P450 include both tyrosine-histidine (A-N-B) and tyrosine-tryptophan (A-O-B) crosslinked tripeptides, the latter a rare example of a phenolic crosslink to an indole moiety. Tripeptides are easily isolated following proteolytic removal of the leader peptide and can incorporate a wide range of amino acids in the residue inside the crosslinked tripeptide. Given the utility of peptide crosslinks in important natural products and the synthetic challenge that these can represent, P450 enzymes have the potential to play roles as important tools in the generation of high-value cyclic tripeptides for incorporation in synthesis, which can be yet further diversified using selective chemical techniques through specific handles contained within these tripeptides.

Data-Driven Colormap Adjustment for Exploring Spatial Variations in Scalar Fields.

Colormapping is an effective and popular visualization technique for analyzing patterns in scalar fields. Scientists usually adjust a default colormap to show hidden patterns by shifting the colors in a trial-and-error process. To improve efficiency, efforts have been made to automate the colormap adjustment process based on data properties (e.g., statistical data value or histogram distribution). However, as the data properties have no direct correlation to the spatial variations, previous methods may be insufficient to reveal the dynamic range of spatial variations hidden in the data. To address the above issues, we conduct a pilot analysis with domain experts and summarize three requirements for the colormap adjustment process. Based on the requirements, we formulate colormap adjustment as an objective function, composed of a boundary term and a fidelity term, which is flexible enough to support interactive functionalities. We compare our approach with alternative methods under a quantitative measure and a qualitative user study (25 participants), based on a set of data with broad distribution diversity. We further evaluate our approach via three case studies with six domain experts. Our method is not necessarily more optimal than alternative methods of revealing patterns, but rather is an additional color adjustment option for exploring data with a dynamic range of spatial variations.

Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation.

The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin (DHA) could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation (IUGR). Twelve normal birth weight (NBW) piglets and 12 piglets with IUGR were fed a basal diet (NBW-CON and IUCR-CON groups), and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg (IUGR-DHA group) from 21 to 49 d of age. At 49 d of age, 8 piglets with similar body weight in each group were sacrificed. The jejunal and ileal samples were collected for further analysis. The results showed that IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated transmembrane toll-like receptor 4 (TLR4)/nucleotide-binding and oligomerization domain (NOD)/nuclear factor-κB (NF-κB) signaling pathway. Dihydroartemisinin inclusion ameliorated intestinal morphology, indicated by increased villus height, villus height-to-crypt depth ratio, villus surface area and decreased villus width of piglets with IUGR (P < 0.05). Compared with NBW piglets, IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression, and lower proliferation index and proliferating cell nuclear antigen expression in the intestine (P < 0.05). Dihydroartemisinin supplementation attenuated the intestinal inflammation of piglets with IUGR, indicated by increased concentrations of intestinal inflammatory cytokines and lipopolysaccharides (P < 0.05). In addition, DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-κB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR (P < 0.05). Piglets in the IUGR-DHA group showed lower protein expressions of TLR4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and higher protein expression of cytoplasmic pNF-κB in the intestine than those in the IUGR-CON group (P < 0.05). In conclusion, DHA supplementation could improve intestinal morphology, regulate enterocyte proliferation and apoptosis, and alleviate intestinal inflammation through TLR4/NOD/NF-κB signaling pathway in weaned piglets with IUGR.

Extraperitoneal Laparoscopic Kidney Transplantation: Preliminary Clinical Experiences from China.

OBJECTIVE: To report on the pioneering clinical experiences of six cases of extraperitoneal laparoscopic kidney transplantation in China. METHODS: For the first time in clinical practice, a customised, controllable double-circulation cooling device was used to protect the transplanted kidney. Of the six patients, two underwent an allograft renal transplantation because they had been diagnosed with uraemia and were on maintenance haemodialysis. The other four patients underwent kidney autotransplantation because of a central renal tumour. RESULTS: The extraperitoneal laparoscopic kidney transplantations were successfully completed between 2017 and 2018. The operative time for the two patients undergoing the allograft transplantation was 3-3.5 h. The time for venous anastomosis was approximately 53-65 min, and the time for arterial anastomosis was approximately 25-30 min. The creatinine level was 90-80 µmol/L after surgery. The operative time of the four patients who underwent autotransplantation was 9.4-17.5 h. The times of venous and arterial anastomosis were 58-90 min and 35-48 min, respectively. The follow-up B-mode ultrasound after surgery showed good blood supply in the spared nephron. A renal graft was removed from one patient 6 months after surgery because of renal atrophy and dysfunction caused by poor blood supply. Five patients (two undergoing allografting and three undergoing autografting) completed the 12-month follow-up, and their renal graft function was good. CONCLUSIONS: Extraperitoneal laparoscopic kidney transplantation, either allograft or autologous transplantation, is a safe and feasible procedure with a good chance of survival for the transplanted kidney. A customised cooling device is effective and practical during laparoscopic kidney transplantation.

Understanding the Glycopeptide Antibiotic Crosslinking Cascade: In Vitro Approaches Reveal the Details of a Complex Biosynthesis Pathway.

The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of in vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of in vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class.

An Effective Cooling Device for Minimal-Incision Kidney Transplantation.

BACKGROUND This study investigated the safety and efficacy of a new cooling device for use in minimal-incision kidney transplantation (MIKT). MATERIAL AND METHODS From June 2016 to December 2021, 9 patients underwent MIKT surgery in our hospitals using the new cooling device to maintain hypothermia. We recorded and analyzed information on the etiology, comorbid status, ongoing renal replacement assessment, BMI, HLA mismatching sites of donors and recipients, and perioperative and postoperative clinical data for recipients. RESULTS Kidney transplantation was successfully performed in all patients. The kidney surface temperature measurement results showed that the intraoperative renal anterior and posterior surface temperatures were stable at approximately 3.8±1.2°C and 5.2±1.3°C, respectively, during ice-water circulation. The mean operation time was 112±15 min, the artery anastomosis time was 16±6.0 min, and the vein anastomosis time was 14±4.5 min. All recipients recovered uneventfully. The patients were followed up for 6-30 months. Urinary and vascular complications were not found in any recipients. CONCLUSIONS The new cooling device can facilitate MIKT. It is safe and feasible to carry out MIKT using the new cooling device, which can reduce surgical trauma and improve the quality of vascular anastomosis with satisfactory cosmetic results.

A Chemoenzymatic Approach to the Synthesis of Glycopeptide Antibiotic Analogues.

Glycopeptide antibiotics (GPAs) are important antibiotics that are highly challenging to synthesise due to their unique and heavily crosslinked structure. Given this, the synthetic production and diversification of this key compound class remains impractical. Furthermore, the possibility of biosynthetic reengineering of GPAs is not yet feasible since the selectivity of the biosynthetic crosslinking enzymes for altered substrates is largely unknown. We show that combining peptide synthesis with enzymatic cyclisation enables the formation of novel examples of GPAs and provides an indication of the utility of these crucial enzymes. By accessing the biosynthetic process in vitro, we identified peptide modifications that are enzymatically tolerated and can also reveal the mechanistic basis for substrate intolerance where present. Using this approach, we next specifically activated modified residues within GPAs for functionalisation at previously inaccessible positions, thereby offering the possibility of late-stage chemical functionalisation after GPA cyclisation is complete.

[Effect of dihydroartemisinin supplementation on inflammation and lipid metabolism induced by lipopolysaccharide in liver of weaned piglets].

To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 µg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1ß, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1ß, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1ß, IL-6, TNF-α, ACCß and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.

Effects of dietary dihydroartemisinin supplementation on growth performance, hepatic inflammation, and lipid metabolism in weaned piglets with intrauterine growth retardation.

The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)-affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR-affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80 mg/kg DHA (IUGR-DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR-affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non-esterified fatty acids (NEFA), very-low-density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway-related genes, whereas that of inflammatory factor-related genes were downregulated. In conclusion, dietary inclusion of 80 mg/kg DHA can alleviate IUGR-induced impairments in piglets.

Exploring the Tetracyclization of Teicoplanin Precursor Peptides through Chemoenzymatic Synthesis.

The glycopeptide antibiotics (GPAs) serve as an important example of the interplay of two powerful enzymatic classes in secondary metabolism: the coupling of nonribosomal peptide synthesis with oxidative aromatic cross-linking performed by cytochrome P450 enzymes. This interplay is responsible for the generation of the highly cross-linked peptide aglycone at the core of this compound class that is required for antibiotic activity and, as such, serves as an important point for the exploration of chemoenzymatic routes to understand the selectivity and mechanism of this complex cascade. Here, we demonstrate the effective reconstitution of enzymatic tetracyclization of synthetic teicoplanin-derived heptapeptides and furthermore discern the importance of the OxyE enzyme in maintaining effective cyclization of such peptides bearing 3,5-dihydroxyphenylglycine residues at position 3 in their structures. These results demonstrate the value of chemically synthesized probes for the elucidation of the enzyme mechanism underpinning the complex process of GPA cyclization and furthermore show the utility of the technique for probing the cyclization of non-natural GPA peptides by these powerful biosynthetic enzymes.

An S wave in ECG lead V6 predicts poor response to cardiac resynchronization therapy and long-term outcome.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a standard treatment for selected patients with chronic heart failure (HF). However, up to 30%-50% of patients still do not respond to CRT. OBJECTIVE: Our aim was to identify the predictive value of an S wave in lead V6 in CRT response in patients with complete left bundle branch block (CLBBB). METHODS: The CLBBB definition included the Strauss left bundle branch block criteria and the absence of q waves in leads I, V5, and V6. According to the electrocardiogram at baseline, CLBBB patients were divided into 3 groups: T-CLBBB group (CLBBB without an S wave in lead V5 or V6), V5S group (CLBBB with an S wave in lead V5 and no S wave in lead V6), and V5&V6S group (CLBBB with S waves in leads V5 and V6). CRT response was defined as left ventricular end-systolic volume reduction ≥ 15% at 6-month follow-up. The combined end point included HF rehospitalization or all-cause death. RESULTS: Of 181 patients with left bundle branch block-like pattern, 112 patients with CLBBB were included into 3 groups: 54 in the T-CLBBB group, 32 in the V5S group, and 26 in the V5&V6S group. The CRT response rate was 85.2% (46), 65.6% (21), and 38.5% (10), respectively (P < .001). Kaplan-Meier curves demonstrated that patients in the V5&V6S group had a higher incidence of HF rehospitalization or all-cause death than those in the other 2 groups (P < .001). In a multivariate logistic regression model analysis, an S wave in lead V6 was significantly associated with CRT nonresponse (hazard ratio 0.33; 95% confidence interval 0.11-0.96; P = .042). CONCLUSION: An S wave in lead V6 can predict poor response to CRT and long-term outcome.

Dietary Curcumin Supplementation Increases Antioxidant Capacity, Upregulates Nrf2 and Hmox1 Levels in the Liver of Piglet Model with Intrauterine Growth Retardation.

Curcumin has improved effects on antioxidant capacity via multiple mechanisms. Intrauterine growth retardation (IUGR) has had adverse influences on human health. IUGR is always associated with elevated oxidative stress and deficiencies in antioxidant defense. Therefore, we chose IUGR piglets as a model to investigate the effects of IUGR on antioxidant capacity of newborn and weaned piglets and determine how these alterations were regulated after supplementation with curcumin in weaned IUGR piglets. In experiment 1, eight normal-birth-weight (NBW) and eight IUGR newborn piglets were selected to determine the effect of IUGR on the antioxidant capacity of neonatal piglets. In experiment 2, thirty-two weaned piglets from four experimental groups: NBW, NC (curcumin supplementation), IUGR, IC (curcumin supplementation) were selected. The results showed that both IUGR newborn and weaned piglets exhibited oxidative damage and lower antioxidant enzymes activities in the liver compared with the NBW piglets. Dietary curcumin supplementation increased body-weight gain, feed intake, activities of antioxidant enzymes, and the expressions of nuclear factor, erythroid 2-like 2 (Nrf2) and heme oxygenase-1 (Hmox1) proteins in the liver of weaned piglets with IUGR. In conclusion, IUGR decreased the antioxidant capacity of newborn and weaned piglets. Curcumin could efficiently improve the growth, increase hepatic antioxidant capacity, and upregulate Nrf2 and Hmox1 levels in the liver of IUGR weaned piglets.

Effect of Curcumin on Growth Performance, Inflammation, Insulin level, and Lipid Metabolism in Weaned Piglets with IUGR.

The possible causes of intrauterine growth retardation (IUGR) might stem from placental insufficiency, maternal malnutrition, inflammation in utero, and other causes. IUGR has had an adverse influence on human health and animal production. Forty weaned piglets with normal birth weights (NBWs) or IUGR were randomly divided into four treatments groups: NBW, NC (NBW with curcumin supplementation), IUGR, and IC (IUGR with curcumin supplementation) from 26 to 50 d. Levels of cytokines, glucose, and lipid metabolism were evaluated. IUGR piglets showed slow growth during the experiment. Piglets with IUGR showed higher levels of serum pro-inflammatory cytokines, insulin resistance, and hepatic lipid accumulation. Curcumin supplementation reduced the production of serum pro-inflammatory cytokines, attenuated insulin resistance and hepatic triglyceride, and enhanced the hepatic glycogen concentrations and lipase activities of IUGR piglets. The hepatic mRNA expressions of the insulin-signaling pathway and lipogenic pathway were influenced by IUGR and were positively attenuated by diets supplemented with curcumin. In conclusion, IUGR caused slow growth, insulin resistance, and increased hepatic lipid levels. Diets supplemented with curcumin improved growth, attenuated insulin resistance, and reduced lipid levels in the liver by regulating the hepatic gene expressions of the related signaling pathway in IUGR piglets.

Dietary Dihydroartemisinin Supplementation Attenuates Hepatic Oxidative Damage of Weaned Piglets with Intrauterine Growth Retardation through the Nrf2/ARE Signaling Pathway.

The object of present study was to evaluate the effects of dihydroartemisinin (DHA) supplementation on the hepatic antioxidant capacity in IUGR-affected weaned piglets. Eight piglets with normal birth weight (NBW) and sixteen IUGR-affected piglets were selected. Piglets were weaned at 21 days. NBW and IUGR groups were fed a basal diet and the ID group was fed the basal diet supplemented with 80 mg/kg DHA for 28 days. The result indicated that compared with NBW piglets, IUGR-affected piglets increased (p < 0.05) the concentration of malondialdehyde (MDA) and decreased (p < 0.05) the serum activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In addition, IUGR-affected piglets showed increased (p < 0.05) hepatic concentrations of protein carbonyl (PC), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and oxidized glutathione (GSSG), and an increased GSSG:GSH value. IUGR-affected piglets exhibited lower (p < 0.05) activities of GSH-Px, T-SOD, total antioxidant capacity (T-AOC), and the concentration of glutathione (GSH). DHA supplementation decreased (p < 0.05) the serum concentration of MDA and increased the serum activities of T-AOC, T-SOD, GSH-Px, and CAT. The ID group showed decreased (p < 0.05) concentrations of MDA, PC, 8-OHdG, and GSSG, and a decreased GSSG:GSH value in the liver. The hepatic activity of T-SOD and the concentration of GSH were increased (p < 0.05) in the liver of ID group. IUGR-affected piglets downregulated (p < 0.05) mRNA expression of nuclear erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and CAT. DHA supplementation increased (p < 0.05) mRNA expression of Nrf2, HO-1, GPx1, and CAT in the ID group. In addition, the protein expression of Nrf2 was downregulated (p < 0.05) in the liver of IUGR-affected piglets and DHA supplementation increased (p < 0.05) the protein content of Nrf2 and HO-1. In conclusion, DHA may be beneficial in alleviating oxidative damage induced by IUGR through the Nrf2/ARE signaling pathway in the liver.