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Herbicide residues in agricultural products can have adverse effects on the environment and human health, therefore, there is an urgent need to establish a sensitive, rapid, and wide-ranging detection method. In this study, haptens of phenylurea herbicides (PUs) and sulfonylurea herbicides (SUs) were analyzed and designed based on computational simulation techniques, and two high-performance broad-spectrum monoclonal antibodies against PUs and SUs were prepared. On this basis, a multi-colloidal gold immunochromatography assay (multi-CGIA) was developed to simultaneously detect 13 herbicides in wheat. The visual limit of detection (vLOD) for PUs including diuron, chlortoluron, neburon, chlorbromuron, and linuron was 1–2 µg/kg. The vLOD for SUs including metsulfuron methyl, ethametsulfuron-methyl, sulfometuron-methyl, tribenuron methyl, cinosulfuron, triasulfuron, chlorimuron-ethyl, and chlorsulfuron was 2–10 µg/kg. The results of real sample determination indicated that the multi-CGIA is accurate, stable, and reliable, and adaptable to on-site preliminary screening of actual samples. [ABSTRACT FROM AUTHOR]

Purpose: Tortuosity of the internal carotid artery (ICA) is associated with intracranial aneurysms (IAs). The siphon is the most curved segment of the ICA, but its morphology has controversial effects on IAs. This study aimed to explore the morphometric features of the siphon and the potential hemodynamic mechanisms that may affect C7 aneurysm formation. Methods: In this study 32 patients with C7 aneurysms diagnosed at Xiangya Hospital between 2019 and 2021 and 32 control subjects were enrolled after propensity score matching. Computed tomography angiography (CTA) images were acquired to measure morphologic features, and then, by combining clinical data, simplified carotid siphon models were constructed, and computational fluid dynamics (CFD) analysis was performed. Results: The presence of C7 aneurysms was associated with the height of the C4–C6 curved arteries (odds ratio [OR] 0.028, 95% confidence interval [CI] 0.003–0.201; P < 0.001). The heights of the C4–C6 curved arteries in the aneurysm group were significantly shorter than those in the control group. The CFD analysis revealed that shorter C4–C6 bends led to greater blood velocity and pressure in the C7 segment arteries. Conclusion: A shorter C4–C6 bend was associated with distal C7 aneurysm formation, and an elaborate hemodynamic mechanism may underlie this association. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) nanoparticles impart outstanding mechanical properties to organic-inorganic nanocomposites in bone. Inspired by the composite structure of HA nanoparticles and collagen in bone, a high performance HA/gelatin nanocomposite was first developed. The nanocomposites have much better mechanical properties (elongation at break 29.9%, tensile strength 90.7 MPa, Young's modulus 5.24 GPa) than pure gelatin films (elongation at break 9.3%, tensile strength 90.8 MPa, Young's modulus 2.5 GPa). In addition, the composite films keep a high transmittance in visible wavelength range from 0% to 60% of the HA solid content. These differences in properties are attributed to the homogeneous distribution of HA nanoparticles in the gelatin polymer matrix and the strong interaction between the particle surfaces and the gelatin molecules. This protocol should be promising for HA-based nanocomposites with enhanced mechanical properties for biomedical applications. [ABSTRACT FROM AUTHOR]

Many problems occur in plain river networks, such as low river flow and severe water environment pollution. Water diversion is important for water environment improvement in plain river network areas. Adopting Sanshanwei in Foshan city as an example, a river network hydrodynamic and water quality coupling model was constructed based on structural optimization technology for complex gate-controlled tidal river networks. Fifteen-day continuous hydrodynamic water quality monitoring data were used for model validation. Two model performance evaluation indices, NSE and RMSE, were employed for model reliability evaluation. Considering terrain, tidal pattern and landscape water level, five optimal scheduling conditions (C1-C5) were designed. The hydrodynamic water quality improvement effect was simulated under different working conditions, and the comprehensive influence mechanisms of tide level, drainage flow and spatial distribution, water quality and river water level were examined. Water pollution was evaluated by a single-factor pollution index. The results indicated a reasonable and reliable model. The river network structure optimization method is universal. Under C1 to C5, the average pollutant reduction rates in the monitoring section were 28.69%, 34.05%, 0.77%, -44.49% and -144.69%. The river network water environment was improved under C1, C2 and C3, from Moderate pollution to Light, Mminor and Light pollution respectively. A river section with high water quality requirements should be used as the upstream section of the water replenishment path. Comprehensively considering the effects of river flow distribution, flow path, branch river diversion and outer river pollutant concentration on river water quality, and combining the dynamic water environment capacity of the tidal river network and spatial and temporal distributions of pollution source discharge, the water environment improvement effect was high significant. These results provide important technical support for water environment management in gate-controlled plain river network areas eliminate black and odorous urban water bodies. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that immunotherapies, including peptide vaccines, remain promising strategies for patients with lower grade glioma (LGG); however new biomarkers need to be developed to identify patients who may benefit from therapy. We aimed to investigate the feasibility of liquid biopsy-based gene signatures in predicting the prognosis of LGG patients, as well as the benefits of immunotherapy. Methods: We evaluated the association between circulating immune cells and treatment response by analyzing peripheral blood mononuclear cell (PBMC) samples from LGG patients receiving peptide vaccine immunotherapy, identified response-related genes (RRGs), and constructed RRG-related Response Score. In addition, RRG-related RiskScore was constructed in LGG tumor samples based on RRGs; association analysis for RiskScore and characteristics of TME as well as patient prognosis were performed in two LGG tumor datasets. The predictive power of RiskScore for immunotherapy benefits was analyzed in an anti-PD-1 treatment cohort. Results: This study demonstrated the importance of circulating immune cells, including monocytes, in the immunotherapeutic response and prognosis of patients with LGG. Overall, 43 significant RRGs were identified, and three clusters with different characteristics were identified in PBMC samples based on RRGs. The constructed RRG-related Response Score could identify patients who produced a complete response to peptide vaccine immunotherapy and could predict prognosis. Additionally, three subtypes were identified in LGG tumors based on RRGs, with subtype 2 being an immune "hot" phenotype suitable for immune checkpoint therapy. The constructed RRG-related RiskScore was significantly positively correlated with the level of tumor immune cell infiltration. Patients with high RiskScore had a worse prognosis and were more likely to respond to immune checkpoint therapy. The therapeutic advantage and clinical benefits of patients with a high RiskScore were confirmed in an anti-PD-1 treatment cohort. Conclusion: This study confirmed the potential of liquid biopsy for individualized treatment selection in LGG patients and determined the feasibility of circulating immune cells as biomarkers for LGG. Scoring systems based on RRGs can predict the benefits of immunotherapy and prognosis in patients with LGG. This work would help to increase our understanding of the clinical significance of liquid biopsy and more effectively guide individualized immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Computational tools for integrative analyses of diverse single-cell experiments are facing formidable new challenges including dramatic increases in data scale, sample heterogeneity, and the need to informatively cross-reference new data with foundational datasets. Here, we present SCALEX, a deep-learning method that integrates single-cell data by projecting cells into a batch-invariant, common cell-embedding space in a truly online manner (i.e., without retraining the model). SCALEX substantially outperforms online iNMF and other state-of-the-art non-online integration methods on benchmark single-cell datasets of diverse modalities, (e.g., single-cell RNA sequencing, scRNA-seq, single-cell assay for transposase-accessible chromatin use sequencing, scATAC-seq), especially for datasets with partial overlaps, accurately aligning similar cell populations while retaining true biological differences. We showcase SCALEX's advantages by constructing continuously expandable single-cell atlases for human, mouse, and COVID-19 patients, each assembled from diverse data sources and growing with every new data. The online data integration capacity and superior performance makes SCALEX particularly appropriate for large-scale single-cell applications to build upon previous scientific insights. Integrative analyses of single-cell datasets are facing new challenges as data size and complexity grow. Here the authors present SCALEX, which projects cells from different datasets into a common latent space, allowing accurate online integration as well as cross-referencing with atlas-scale data. [ABSTRACT FROM AUTHOR]

Minimizing the wear of the surfaces exposed to mechanical shear stresses is a critical challenge for maximizing the lifespan of rotary mechanical parts. In this study, we have discovered the anti-wear capability of a series of metal nitride-copper nanocomposite coatings tested in a liquid hydrocarbon environment. The results indicate substantial reduction of the wear in comparison to the uncoated steel substrate. Analysis of the wear tracks indicates the formation of carbon-based protective films directly at the sliding interface during the tribological tests. Raman spectroscopy mapping of the wear track suggests the amorphous carbon (a-C) nature of the formed tribofilm. Further analysis of the tribocatalytic activity of the best coating candidate, MoN-Cu, as a function of load (0.25–1 N) and temperature (25 °C and 50 °C) was performed in three alkane solutions, decane, dodecane, and hexadecane. Results indicated that elevated temperature and high contact pressure lead to different tribological characteristics of the coating tested in different environments. The elemental energy dispersive x-ray spectroscopy analysis and Raman analysis revealed formation of the amorphous carbon film that facilitates easy shearing at the contact interface thus enabling more stable friction behavior and lower wear of the tribocatalytic coating. These findings provide new insights into the tribocatalysis mechanism that enables the formation of zero-wear coatings. [ABSTRACT FROM AUTHOR]

Meningiomas are the most commonly diagnosed benign intracranial adult tumors. Subsets of meningiomas that present with extensive invasion into surrounding brain areas have high recurrence rates, resulting in difficulties for complete resection, substantially increased mortality of patients, and are therapeutically challenging for neurosurgeons. Exciting new data have provided insights into the understanding of the molecular machinery of invasion. Moreover, clinical trials for several novel approaches have been launched. Here, we will highlight the mechanisms which govern brain invasion and new promising therapeutic approaches for brain-invasive meningiomas, including pharmacological approaches targeting three major aspects of tumor cell invasion: extracellular matrix degradation, cell adhesion, and growth factors, as well as other innovative treatments such as immunotherapy, hormone therapy, Tumor Treating Fields, and biodegradable copolymers (wafers), impregnated chemotherapy. Those ongoing studies can offer more diversified possibilities of potential treatments for brain-invasive meningiomas, and help to increase the survival benefits for patients. [ABSTRACT FROM AUTHOR]

As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial-mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response. [ABSTRACT FROM AUTHOR]

N and P concentrations and their ratios were determined for 132 foliar and 120 below-ground biomass (BGB) samples obtained at 132 sites along the 4500 km Chinese Grassland Transect (CGT) across the Inner Mongolian and Qinghai-Tibet Plateaus. Patterns of foliar and BGB N, P and their ratio (N/P) at the community level were related to altitude, temperature, and precipitation gradients. Also, patterns of relative N and P foliar and BGB concentrations were determined (N, foliar N/BGB N; P, foliar P/BGB P). The relationship between foliar N concentrations and mean annual temperature (MAT) was negative, agreeing with the Temperature-Plant Physiological hypothesis, whereas BGB N decreased with decreasing MAT, supporting the Biogeochemical hypothesis. Patterns of BGB N varying with altitude, MAP and MAT differed from the patterns for leaf N, which may indicate differences in nutrient allocation and utilization by leaves and BGB. N and P may reflect trade-offs by plants for N and P in leaves and BGB. For the entire CGT, N and P increased as altitude increased. N was positively related with MAP but negatively related with MAT, while P showed no correlations with MAP and MAT. Results suggest that ecological stoichiometry at the community level is similar to that at the species level. Strategies of nutrient utilization by leaves and BGB are indicated to be different, and abiotic environmental conditions could influence the stoichiometric characteristics and nutrient allocation to leaves and BGB. [ABSTRACT FROM AUTHOR]

Water-use efficiency (WUE), which links carbon and water cycles, is an important indicator of assessing the interactions between ecosystems and regional climate. Using chamber methods with and without plant removal treatments, we investigated WUE and evapotranspiration (ET) components in three ecosystems with different land-use types in Northern China pastoral-farming ecotone. In comparison, ET of the ecosystems with grazing exclusion and cultivating was 6.7 and 13.4 % higher than that of the ecosystem with free grazing. The difference in ET was primarily due to the different magnitudes of soil water evaporation (E) rather than canopy transpiration (T). Canopy WUE (WUEc, i.e., the ratio of gross primary productivity to T) at the grazing excluded and cultivated sites was 17 and 36 % higher than that at the grazing site. Ecosystem WUE (WUEnep, i.e., the ratio of net ecosystem productivity to ET) at the cultivated site was 34 and 28 % lower in comparison with grazed and grazing excluded stepped, respectively. The varied leaf area index (LAI) of different land uses was correlated with microclimate and ecosystem vapor/carbon exchange. The LAI changing with land uses should be the primary regulation of grassland WUE. These findings facilitate the mechanistic understanding of carbon-water relationships at canopy and ecosystem levels and projection of the effects of land-use change on regional climate and productivity. [ABSTRACT FROM AUTHOR]

Schistosomiasis threatens thousands of millions of peoples' health every year in the world. Schistosoma japonicum, a pathogen of schistosomiasis, is covered by a lipid bilayer membrane which plays an important role in nutrient transport, signal transduction, interaction with host's immune system, etc. Thus, molecules in the tegumental membrane have gained more and more interest for understanding biological and pathological processes of schistosoma. In this study, we found a protein from S. japonicum cDNA library which has a 20.8 KDa molecular weight (SjTP20.8). Recombinant SjTP20.8 was produced and purified from Escherichia coli. The recombinant protein could be detected by S. japonicum-infected mice and human sera, and it had been found localizing in the tegumental membrane of S. japonicum in the section using immunofluorescence assay. In electrophoretic mobility shift assay, the protein could bind calcium iron in neutral condition. Result of cercariae challenge experiment indicates antibody against this protein can protect mice from chronic hepatic fibrosis. Our results indicate the S. japonicum tegumental protein 20.8 is crucial for the parasite's calcium absorbing and reproduction. [ABSTRACT FROM AUTHOR]

Purpose: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients.A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed.Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed.Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.Methods: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients.A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed.Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed.Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.Results: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients.A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed.Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed.Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level.Conclusions: DNA mismatch repair (MMR) protein deficiency has attached more attention for its potential to be a biomarker of immunotherapy for colorectal cancer (CRC) patients. However, clinical models involving the expression status of MMR protein are rare. Herein, we sought to develop two clinical models (a diagnostic model for the prediction of MMR status and a prognostic model for the prediction of disease-free survival) for CRC patients.A total of 582 CRC patients were finally included. There were 53 patients with deficient expression of MMR protein. The differences between the deficient MMR (dMMR) group and the proficient MMR (pMMR) group were analyzed.Compared to pMMR patients, those with dMMR status were younger and had better pathological features (depth of invasion, lymph node metastasis, distant metastasis, pathological stage, perineuronal invasion, and PLT level) and disease-free survival (DFS). The tumor location of the left colon, adenocarcinoma, and abnormal PLT level were identified as the independent predictors for pMMR. Based on these data, we developed the diagnostic model using Logistic regression analysis. It showed a satisfactory accuracy (AUC = 82.3% in the derivate set; AUC = 73.6% in the validation set). Furthermore, pMMR, poorer differentiation, perineuronal invasion, distant metastasis, lower hemoglobin level, and abnormal CEA level were established as the independent prognostic factors of poorer DFS. Based on them, a prognostic model with valuable performance (1-year AUC = 75.5%/3-year AUC = 76.9% in the derivate set; 1-year AUC = 72.3%/3-year AUC = 73.8% in the validation set) was developed.Our diagnostic and prognostic models could identify CRC patients at risk for pMMR protein expression and disease recurrence. It may contribute to improving the diagnosis and treatment of CRC patients at an individual level. [ABSTRACT FROM AUTHOR]

Clonorchiasis, caused by Clonorchis sinensis infection, is a zoonotic parasitic disease of hepatobiliary system in which the proteins released by adult are major pathogenetic factors. In this study, we first characterized a putative sphingomyelin phosphodiesterase ( CsSMPase) A-like secretory protein, which was highly expressed in the adult worm. The full-length gene was cloned. The putative protein is of relatively low homology comparing with SMPase from other species, and of rich T cell and B cell epitopes, suggesting that it is an antigen of strong antigenicity. The complete coding sequence of the gene was expressed in the Escherichia coli. The recombinant CsSMPase (r CsSMPase) can be recognized by C. sinensis-infected serum, and the protein immunoserum can recognize a specific band in excretory/secretory products (ESPs) of C. sinensis adult by western blotting. Immunolocalization revealed that CsSMPase was not only localized on tegument, ventral sucker of metacercaria, and the intestine of adult but also on the nearby epithelium of bile duct of the infected Sprague-Dawley rats, implying that CsSMPase was mainly secreted and excreted through adult intestine and directly interacted with bile duct epithelium. Although immunized rats evoked high level antibody response, the antigen level was low in clonorchiasis patients. And the sensitivity and specificity of r CsSMPase were 50.0 % (12/24) and 88.4 % (61/69), in sera IgG-ELISA, respectively. It is likely due to the fact that CsSMPase binding to the plasma membrane of biliary epithelium decreases the antigen immune stimulation. [ABSTRACT FROM AUTHOR]

Background and aim: Because the indigenous burrowing lagomorph plateau pika ( Ochotona curzoniae) is considered to have negative ecological impacts on alpine meadow steppe grasslands of the Headwaters Region of the Yellow, Yangtze and Mekong Rivers we investigated its effects on ecosystem productivity and soil properties, and especially net ecosystem carbon flux. Methods: We measured net ecosystem CO exchange (NEE) and its components gross ecosystem productivity (GEP) and ecosystem respiration (ER) at peak aboveground biomass by the chamber method with reference to plant and soil characteristics of areas of alpine meadow steppe with different densities of pika burrows. Results: Higher burrow density decreased NEE, GEP and ER. Above-ground biomass, species number, plant cover and leaf area index decreased with increasing pika density. Higher burrow density was associated with lower soil moisture and higher soil temperature. Responses of NEE were related to changes of abiotic and biotic factors affecting its two components. NEE was positively related to soil moisture, soil ammonium nitrogen, plant cover, leaf area index and above-ground biomass but was negatively correlated with higher soil nitrate nitrogen. Conclusion: Decrease of NEE by plateau pika may reduce the carbon sink balance of Qinghai-Tibet plateau grassland. Such effects may be influenced by grazing pressure from domestic livestock, population levels of natural predators, and climate change. [ABSTRACT FROM AUTHOR]

Antigen 5 (Ag5) has been identified as a dominant component of cyst fluid of Echinococcus granulosus and is considered as a member of serine proteases family, which in other helminth, plays an important role in the egg hatch and larva invasion. However, whether Ag5 is expressed and secreted in all life stages is unknown. In this study, according to the sequence in GenBank, we cloned and sequenced the open reading frame (ORF) of Ag5 gene from the protoscolices of E. granulosus isolated from the sheep in Qinhai Province of China, and found several substitutions and a base insert and deletion in a short region near the stop code, leading to a frameshift mutation which is conserved with the homologue of other cestode. The ORF is 1,455 bp in length, encoding 484 amino acids with a secretory signal peptide. Bioinformatics analysis predicted several phosphorylation and myristoylation sites and a N-glycosylation site and a species-specific linear B epitope in the protein. The ORF was cloned into the plasmid pET28a(+) vector and expressed in Escherichia coli . The recombinant protein was purified by affinity chromatography. Anti-rEgAg5 antiserum was prepared in rats and used to analyze the localization of Ag5 in protoscolex and adult worm by immunofluorescence technique. Results demonstrated that the Ag5 is strongly expressed in the tegument of protoscolex and the embryonic membrane of egg and surface of oncosphere; meanwhile, it is also weakly expressed in tegument of the adult. This study showed that Ag5 is expressed in all stages of life cycle, secreted from the surface of the worm and may be anchored in membrane by its myristoylation sites; these characteristics make it a candidate antigen for diagnosis and vaccine for both intermediate and definitive hosts. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA) mainly injures the reproductive system of mammals. In the present study, we aimed to explore the mechanism by which zinc inhibits ZEA-induced reproductive damage in KK-1 cells for the first time. The results shown that both zinc sulfate and zinc gluconate addition increased the intracellular zinc concentration and influenced the expression of zinc transporters (Slc30a1 and Slc39a1) in a time-dependent manner. Co-incubation of zinc with ZEA significantly reduced the ZEA-induced reactive oxygen species and malondialdehyde elevation by promoting the transcription of Mtf1 and Mt2. Meanwhile, two different zincs inhibited the ZEA-induced loss of mitochondrial membrane potential and elevation of late-stage apoptosis via activating the mitochondrial apoptotic pathway by recovering the mRNA and protein expression of pro-apoptotic genes (Bax, Casp3, Casp9). Zinc also recovered cells from S-phase cell cycle arrest. In addition, both of them promoted the ZEA-induced estrogen production but regulated the expression of steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp17a1) in different way. All these results indicated that zinc could inhibit the reproductive toxicity of ZEA. [ABSTRACT FROM AUTHOR]

Oxidative stress and apoptosis are involved in Ochratoxin A (OTA)-induced renal cytotoxicity. Apoptosis signal-regulating kinase 1 (ASK1) is a Mitogen-Activated Protein Kinase Kinase Kinase (MAPKKK, MAP3K) family member that plays an important role in oxidative stress-induced cell apoptosis. In this study, we performed RNA interference of ASK1 in HEK293 cells and employed an iTRAQ-based quantitative proteomics approach to globally investigate the regulatory mechanism of ASK1 in OTA-induced renal cytotoxicity. Our results showed that ASK1 knockdown alleviated OTA-induced ROS generation and Δψm loss and thus desensitized the cells to OTA-induced apoptosis. We identified 33 and 24 differentially expressed proteins upon OTA treatment in scrambled and ASK1 knockdown cells, respectively. Pathway classification and analysis revealed that ASK1 participated in OTA-induced inhibition of mRNA splicing, nucleotide metabolism, the cell cycle, DNA repair, and the activation of lipid metabolism. We concluded that ASK1 plays an essential role in promoting OTA-induced renal cytotoxicity. [ABSTRACT FROM AUTHOR]