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Introduction: In Northeast China, Dorper and Australian White rams are commonly crossbred with small-tailed Han (STH) ewes to improve the offspring's meat yield and quality. However, the differences in traits and the flavor between the crossbred sheep and STH sheep remain unclear. In addition, the candidate genes potentially influencing the meat quality in the three sheep breeds require further verification. Methods: A total of 18 2-month-old healthy rams were raised over a period of 5 months, which included 6 STH, 6 Dorper and small-tailed Han crossbred (Do × STH), and 6 Australian white and small-tailed Han crossbred (Au × STH) offspring. The differences in slaughter, meat quality traits, fatty acid and amino acid composition in the muscular longissimus dorsi (MLD), and volatile compounds in the semitendinosus muscle were compared between the sheep breeds. The candidate genes related to intramuscular fat (IMF) content and fatty acids were validated. Results: The results of this study revealed that the crossbred sheep had higher body weight, carcass weight, bone weight, net meat weight, and IMF content than the STH sheep (p < 0.05). The Do × STH offspring had a higher pH value (24 h), moisture content, and cooking percentage; they also had redder and brighter meat color. The content of myristate, palmitic, and margaric acids in the crossbred sheep was higher than that in the STH sheep (p < 0.05). The Do × STH offspring had the highest saturated fatty acid content (p < 0.05). The Au × STH offspring had the highest protein content (p < 0.05). The arachidonic acid and amino acid (Asp, Ala, Ile, Leu, Lys, Thr, and essential amino acid) contents were higher in the STH sheep than in the crossbred sheep (p < 0.05). The odor activity value (OAV) analysis showed that most of the aldehydes in the Au × STH offspring had higher values. The PDK4 gene expression was positively associated with the IMF content and was negatively correlated with the linoleic acid content in the Do × STH sheep (p < 0.05). The TMEM273 gene expression was positively associated with linoleic and arachidonic acid contents and was negatively correlated with oleic and palmitic acid contents in the Do × STH sheep (p < 0.05). Discussion: The results showed the differences between the crossbred sheep and STH sheep and provided the candidate genes related to meat quality in sheep.
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BACKGROUND: The neuropathic pain with complex networks of neuroinflammatory activation severely limits clinical therapeutic research. TNF receptor-associated factor 6 (TRAF6) is associated with multiple inflammatory diseases. However, there remains confusion about the effects and mechanisms of TRAF6 in neuropathic pain. METHODS: A chronic constriction injury (CCI) model was developed to simulate neuralgia in vivo. We overexpressed or knocked down TRAF6 in CCI mice, respectively. Activation of microglia by TRAF6, the inflammatory response, and disease progression were inspected using WB, qRT-PCR, immunofluorescence, flow cytometry, and ELISA assays. Moreover, the mechanism of M1/M2 polarization activation of microglia by TRAF6 was elaborated in BV-2 cells. RESULTS: TRAF6 was enhanced in the spinal neurons and microglia of the CCI mice model compared with the sham operation group.. Down-regulation of TRAF6 rescued the expression of Iba-1. In response to mechanical and thermal stimulation, PWT and PWL were improved after the knockdown of TRAF6. Decreased levels of pro-inflammatory factors were observed in TRAF6 knockdown groups. Meanwhile, increased microglial M1 markers induced by CCI were limited in mice with TRAF6 knockdown. In addition, TRAF6 overexpression has the precise opposite effect on CCI mice or microglia polarization. We also identifed that TRAF6 activated the c-JUN/NF-kB pathway signaling; the inhibitor of c-JUN/NF-kB could effectively alleviate the neuropathic pain induced by upregulated TRAF6 in the CCI mice model. CONCLUSION: In summary, this study indicated that TRAF6 was concerned with neuropathic pain, and targeting the TRAF6/c-JUN/NF-kB pathway may be a prospective target for treating neuropathic pain.
Subject(s)
Microglia , NF-kappa B , Neuralgia , Signal Transduction , TNF Receptor-Associated Factor 6 , Animals , Male , Mice , Cell Line , Cell Polarity , Disease Models, Animal , Mice, Inbred C57BL , Microglia/metabolism , Neuralgia/metabolism , NF-kappa B/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , TNF Receptor-Associated Factor 6/metabolismABSTRACT
Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.
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Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.
Subject(s)
Copper , Liver , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Animals , Male , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Mice , Copper/blood , Liver/metabolism , Lipid Metabolism , Gastrointestinal Microbiome/drug effects , Disease Models, Animal , Probiotics/administration & dosage , Probiotics/pharmacology , Metabolomics , Lactobacillus plantarum , Lipidomics , MultiomicsABSTRACT
Analysis of integrated data often requires record linkage in order to join together the data residing in separate sources. In case linkage errors cannot be avoided, due to the lack a unique identity key that can be used to link the records unequivocally, standard statistical techniques may produce misleading inference if the linked data are treated as if they were true observations. In this paper, we propose methods for categorical data analysis based on linked data that are not prepared by the analyst, such that neither the match-key variables nor the unlinked records are available. The adjustment is based on the proportion of false links in the linked file and our approach allows the probabilities of correct linkage to vary across the records without requiring that one is able to estimate this probability for each individual record. It accommodates also the general situation where unmatched records that cannot possibly be correctly linked exist in all the sources. The proposed methods are studied by simulation and applied to real data.
Subject(s)
Computer Simulation , Medical Record Linkage , Models, Statistical , Humans , Medical Record Linkage/methods , Data Interpretation, Statistical , ProbabilityABSTRACT
A simple and stable cataluminescence (CTL) sensing platform based on a single sensing material for effective and rapid detection of aldehydes is an urgent need due to growing concerns for the environment, security, and health. Here, an effective and user-friendly identification method is successfully proposed to determine six common aldehydes of homologous compounds via a heterothermic CTL sensor system. Using Gd2O3 with excellent catalytic activity as a sensing material, thermodynamic and kinetic insights into the interactions between Gd2O3 and aldehydes at different temperatures were extracted and integrated to generate a unique constellation profile for each tested aldehyde, whereby achieving their effective and prompt determination. Moreover, the sensor system allowed the quantitative analysis of aldehydes with detection limits of 0.001, 0.009, 0.011, 0.011, 0.007, and 0.003 µg mL-1. Significantly, the sensor system had an excellent stability of up to 30 days. The CTL sensing platform was constructed based on a thermal regulation strategy that can provide a new approach to chemical agent identification.
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Microbial organic matter turnover is an important contributor to the terrestrial carbon dioxide (CO2) budget. Partitioning of organic carbons into biomass relative to CO2 efflux, termed carbon-use efficiency (CUE), is widely used to characterize organic carbon cycling by soil microorganisms. Recent studies challenge proposals of CUE dependence on the oxidation state of the substrate carbon and implicate instead metabolic strategies. Still unknown are the metabolic mechanisms underlying variability in CUE. We performed a multiomics investigation of these mechanisms in Pseudomonas putida, a versatile soil bacterium of the Gammaproteobacteria, processing a mixture of plant matter derivatives. Our 13C-metabolomics data captured substrate carbons into different metabolic pathways: cellulose-derived sugar carbons in glycolytic and pentose-phosphate pathways; lignin-related aromatic carbons in the tricarboxylic acid cycle. Subsequent 13C-metabolic flux analysis revealed a 3-fold lower investment of sugar carbons in CO2 efflux compared to aromatic carbons, in agreement with reported substrate-dependent CUE. Proteomics analysis revealed enzyme-level regulation only for substrate uptake and initial catabolism, which dictated downstream fluxes through CO2-producing versus biomass-synthesizing reactions. Metabolic partitioning as shown here explained the substrate-dependent CUE calculated from reported metabolic flux analyses of other bacteria, further supporting a metabolism-guided perspective for predicting the microbial conversion of accessible organic matter to CO2 efflux.
Subject(s)
Carbon Dioxide , Carbon , Carbon Dioxide/metabolism , Carbon/metabolism , Metabolic Networks and Pathways , Pseudomonas putida/metabolism , BiomassABSTRACT
Microbial sulfate reduction is central to the global carbon cycle and the redox evolution of Earth's surface. Tracking the activity of sulfate reducing microorganisms over space and time relies on a nuanced understanding of stable sulfur isotope fractionation in the context of the biochemical machinery of the metabolism. Here, we link the magnitude of stable sulfur isotopic fractionation to proteomic and metabolite profiles under different cellular energetic regimes. When energy availability is limited, cell-specific sulfate respiration rates and net sulfur isotope fractionation inversely covary. Beyond net S isotope fractionation values, we also quantified shifts in protein expression, abundances and isotopic composition of intracellular S metabolites, and lipid structures and lipid/water H isotope fractionation values. These coupled approaches reveal which protein abundances shift directly as a function of energy flux, those that vary minimally, and those that may vary independent of energy flux and likely do not contribute to shifts in S-isotope fractionation. By coupling the bulk S-isotope observations with quantitative proteomics, we provide novel constraints for metabolic isotope models. Together, these results lay the foundation for more predictive metabolic fractionation models, alongside interpretations of environmental sulfur and sulfate reducer lipid-H isotope data.
Subject(s)
Desulfovibrio vulgaris , Proteomics , Sulfur Isotopes , Sulfur Isotopes/analysis , Sulfur Isotopes/metabolism , Desulfovibrio vulgaris/metabolism , Proteome/metabolism , Proteome/analysis , Energy Metabolism , Metabolome , Bacterial Proteins/metabolism , Oxidation-Reduction , Sulfates/metabolismABSTRACT
Zinc gallium oxide (ZnGa2O4) has attracted considerable interest in deep-ultraviolet photodetectors, due to the ultrawide bandgap, high transmittance in the ultraviolet (UV) region, and excellent environmental stability. In this study, ZnGa2O4 thin films were deposited on p-GaN epi-layers using pulsed laser deposition, resulting in improved crystalline quality. The ZnGa2O4 film exhibited a bandgap of 4.93â eV, calculated through absorption spectra. A heterojunction photodetector (PD) was constructed, demonstrating a rectification effect, an on/off ratio of 12,697 at -5.87â V, a peak responsivity of 14.5â mA/W, and a peak detectivity of 1.14 × 1012 Jones (262â nm, -6â V). The PD exhibited a fast response time (39â ms) and recovery time (30â ms) under 262â nm illumination. The band diagram based on the Anderson model elucidates the photoresponse and carrier transport mechanism. This work paves the way for advancing next-generation optoelectronics.
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PURPOSE: Patients with age-related hearing loss complain often about reduced speech perception in adverse listening environment. Studies on animals have suggested that cochlear synaptopathy may be one of the primary mechanisms responsible for this phenomenon. A decreased wave I amplitude in supra-threshold auditory brainstem response (ABR) can diagnose this pathology non-invasively. However, the interpretation of the wave I amplitude in humans remains controversial. Recent studies in mice have established a robust and reliable mathematic algorithm, i.e., curve curvature quantification, for detecting cochlear synaptopathy. This study aimed to determine whether the curve curvature has sufficient test-retest reliability to detect cochlear synaptopathy in aging humans. METHODS: Healthy participants were recruited into this prospective study. All subjects underwent an audiogram examination with standard and extended high frequencies ranging from 0.125 to 16 kHz and an ABR with a stimulus of 80 dB nHL click. The peak amplitude, peak latency, curvature at the peak, and the area under the curve of wave I were calculated and analyzed. RESULTS: A total of 80 individuals with normal hearing, aged 18 to 61 years, participated in this study, with a mean age of 26.4 years. Pearson correlation analysis showed a significant negative correlation between curvature and age, as well as between curvature and extended high frequency (EHF) threshold (10-16 kHz). Additionally, the same correlation was observed between age and area as well as age and EHF threshold. The model comparison demonstrated that the curvature at the peak of wave I is the best metric to correlate with EHF threshold. CONCLUSION: The curvature at the peak of wave I is the most sensitive metric for detecting cochlear synaptopathy in humans and may be applied in routine diagnostics to detect early degenerations of the auditory nerve.
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In light of deep tissue penetration and ultralow background, near-infrared (NIR) persistent luminescence (PersL) bioprobes have become powerful tools for bioapplications. However, the inhomogeneous signal attenuation may significantly limit its application for precise biosensing owing to tissue absorption and scattering. In this work, a PersL lifetime-based nanoplatform via deep learning was proposed for high-fidelity bioimaging and biosensing in vivo. The persistent luminescence imaging network (PLI-Net), which consisted of a 3D-deep convolutional neural network (3D-CNN) and the PersL imaging system, was logically constructed to accurately extract the lifetime feature from the profile of PersL intensity-based decay images. Significantly, the NIR PersL nanomaterials represented by Zn1+xGa2-2xSnxO4: 0.4 % Cr (ZGSO) were precisely adjusted over their lifetime, enabling the PersL lifetime-based imaging with high-contrast signals. Inspired by the adjustable and reliable PersL lifetime imaging of ZGSO NPs, a proof-of-concept PersL nanoplatform was further developed and showed exceptional analytical performance for hypochlorite detection via a luminescence resonance energy transfer process. Remarkably, on the merits of the dependable and anti-interference PersL lifetimes, this PersL lifetime-based nanoprobe provided highly sensitive and accurate imaging of both endogenous and exogenous hypochlorite. This breakthrough opened up a new way for the development of high-fidelity biosensing in complex matrix systems.
Subject(s)
Biosensing Techniques , Deep Learning , Hypochlorous Acid , Biosensing Techniques/methods , Hypochlorous Acid/analysis , Luminescence , Infrared Rays , Humans , Animals , Nanostructures/chemistry , Luminescent Measurements/methods , MiceABSTRACT
Self-powered deep ultraviolet photodetectors (DUV PDs) are essential in environmental monitoring, flame detection, missile guidance, aerospace, and other fields. A heterojunction photodetector based on p-CuI/n-ZnGa2O4 has been fabricated by pulsed laser deposition combined with vacuum thermal evaporation. Under 260â nm DUV light irradiation, the photodetector exhibits apparent self-powered performance with a maximum responsivity and specific detectivity of 2.75â mA/W and 1.10 × 1011 Jones at 0â V. The photodetector exhibits high repeatability and stability under 260â nm periodic illumination. The response and recovery time are 205â ms and 133â ms, respectively. This work provides an effective strategy for fabricating high-performance self-powered DUV photodetectors.
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Ultraviolet (UV) photodetector plays an important role in military, civilian and people's daily life, and is an indispensable part of spectral detection. However, photodetectors target at the UVB region (280-320â nm) are rarely reported, and the devices detected by medium-wave UV light generally have problems such as low detection rate, low sensitivity, and poor stability, which are difficult to meet the market application needs. Herein, Cs-Cu-I films with mixed-phase have been prepared by vacuum thermal evaporation. By adjusting the proportion of evaporation sources (CsI and CuI), the optical bandgaps of mixed-phase Cs-Cu-I films can be tuned between 3.7â eV and 4.1â eV. This absorption cut-off edge is exactly at both ends of the UVB band, which indicating its potential application in the field of UVB detection. Finally, the photodetectors based on Cs-Cu-I/n-Si heterojunction are fabricated. The photodetector shows good spectral selectivity for UVB band, and has a photoresponsivity of 22â mA/W, a specific detectivity of 1.83*1011 Jones, an EQE over 8.7% and an on/off ratio above 20.
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To the deep tissue penetration and ultra-low background, developing near-infrared (NIR) chemiluminescence probes for human health and environmental safety has attracted more and more attention, but it remains a huge challenge. Herein, a novel NIR chemiluminescence (CL) system was rationally designed and developed, utilizing Cr3+-activated ZnGa2O4 (ZGC) nanoparticles as a catalytic luminophore via hypochlorite (NaClO) activation for poisonous target (hydrazine, N2H4) detection. With superior optical performance and unique catalytic structure of ZGC nanoparticles, the fabricated ZGC-NaClO-N2H4 CL system successfully demonstrated excellent NIR emission centered at 700 nm, fast response, and high sensibility (limit of detection down to 0.0126 µM). Further experimental studies and theoretical calculations found the cooperative catalytic chemiluminescence resonance energy transfer mechanism in the ZGC-NaClO-N2H4 system. Remarkably, the ZGC-based NIR CL system was further employed for N2H4 detection in a complicated matrix involving bioimaging and real water samples, thereby opening a new way as a highly reliable and accurate tool in biomedical and environmental monitoring applications.
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Inhibiting oxidative stress is key for ensuring sperm motility during semen cryopreservation. The aim of this study was to investigate the effect of adding alpha-lipoic acid (ALA) as an extender in rooster semen cryopreservation. Different concentrations of ALA were added to the frozen diluent of rooster semen; subsequently, computer-aided semen analysis was used to determine membrane functional integrity, acrosome integrity, antioxidant capacity (based on T-AOC, GSH-Px, SOD, CAT, and MDA contents), and mitochondrial integrity. The frozen sperm ultrastructure was observed using transmission electron microscopy. The results showed that the addition of different concentrations of ALA partially to greatly improved the quality of frozen sperm; in particular, 8 µg/mL ALA significantly improved multiple parameters of sperm quality, including sperm motility and antioxidant enzyme activity, after freeze-thaw. The results of this study provide empirical and theoretical support for effective rooster semen cryopreservation and can inform the development of new protective agents in the field of livestock reproduction.
Subject(s)
Antioxidants , Chickens , Cryopreservation , Oxidative Stress , Semen Preservation , Thioctic Acid , Animals , Cryopreservation/veterinary , Semen Preservation/veterinary , Semen Preservation/methods , Male , Thioctic Acid/pharmacology , Oxidative Stress/drug effects , Chickens/physiology , Antioxidants/pharmacology , Semen Analysis/veterinary , Cryoprotective Agents/pharmacology , Semen/drug effects , Semen/physiology , Spermatozoa/drug effects , Spermatozoa/physiology , Sperm Motility/drug effectsABSTRACT
OBJECTIVE: Accurate positioning of the electrode array during cochlear implant (CI) surgery is crucial for achieving optimal hearing outcomes. Traditionally, postoperative radiological imaging has been used to assess electrode position. Transimpedance matrix (TIM) measurements have also emerged as a promising method for assessing electrode position. This involves utilizing electric field imaging to create an electric distance matrix by analyzing voltage variations among adjacent electrodes. This study aimed to investigate the feasibility of using intraoperative TIM measurements to estimate electrode position and monitor postoperative changes. STUDY DESIGN: Retrospective cohort study. SETTING: University Medical center, tertiary academic referral center. PATIENTS: Patients undergoing CI (CI622) surgery between January 2019 and June 2022. INTERVENTION: CI electrode positions and maximal angular insertion depths (maxAID) were determined using X-ray imaging according to Stenvers' projection. The mean gradient phase (MGP) was extracted from the TIM, and a correlation between the MGP and maxAID was examined. A model was then built to estimate the maxAID using the MGP, and changes in electrode location over time were assessed using this model. MAIN OUTCOME MEASURES: Twenty-four patients were included in this study. A positive correlation between the maxAID and the MGP ( R = 0.7, p = 0.0001) was found. The established model was able to predict the maxAID with an accuracy of 27.7 ± 4.4°. Comparing intraoperative and postoperative TIM measurements, a decrease of 24.1° ± 10.7° in maxAID over time was observed. CONCLUSION: TIM measurements are useful for estimating the insertion depth of the electrode and monitoring changes in the electrode's position over time.
Subject(s)
Cochlear Implantation , Cochlear Implants , Humans , Retrospective Studies , Cochlear Implantation/methods , Hearing , Radiography , Electrodes, Implanted , Cochlea/surgeryABSTRACT
Cardiovascular disease (CVD) has been the leading cause of death worldwide. As a chronic inflammatory disease, atherosclerosis (AS) acts as the initiating factor for CVD and reactive oxygen species (ROS) play a vital role in its development. Superoxide dismutases (SOD) can alleviate the detrimental effects of ROS and serve as the first line of defense through detoxifying the products derived from oxidative stress in vivo. Considering the potential preventive effects of high-density lipoprotein (HDL) on AS and the close relationship between CuZn superoxide dismutase (CuZnSOD) and HDL, the present work investigated whether CuZnSOD overexpression in swine could improve the function of HDL. Seven CuZnSOD transgenic swine, constructed by sperm and magnetic nanoparticles, demonstrated overexpressed CuZnSOD in the liver (P < 0.01) but comparable level to control in plasma (P > 0.05). CuZnSOD overexpression significantly down-regulated the levels of triglyceride (TG), apolipoprotein A-I (apoA-I) (P < 0.05), and high-density lipoprotein cholesterol (HDL-C) (P < 0.01) in plasma. In the presence of CuZnSOD overexpression, HDL3 significantly inhibited levels of IL-6 and TNF-α induced by oxidized low-density lipoprotein (oxLDL) (P < 0.05), indicating enhanced anti-inflammatory activity of HDL. At the same time, HDL-mediated cholesterol efflux did not decrease (P > 0.05). CuZnSOD overexpression improves the anti-inflammatory function of HDL despite decreased levels of HDL-C. In Conclusion, CuZnSOD overexpression improves HDL function in swine.
Subject(s)
Lipoproteins, HDL , Superoxide Dismutase , Animals , Swine , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Lipoproteins, HDL/metabolism , Animals, Genetically Modified , Interleukin-6/metabolism , Interleukin-6/genetics , Apolipoprotein A-I/metabolism , Apolipoprotein A-I/genetics , Male , Liver/metabolism , Triglycerides/metabolism , Triglycerides/bloodABSTRACT
Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.