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Iron (Fe), an essential trace element, plays a key role in biological metabolism. The PI3K/AKT/mTOR axis plays an important role in the control of apoptosis. However, the effect of iron overdose in the diet on the role of the PI3K/AKT/mTOR axis and apoptosis, and pathological liver damage in chickens are still poorly understood. In this study, 180 1-day-old chicks were divided into 3 groups, which were fed the basal diets supplemented with 50 (C), 500 (E1), and 1000 (E2) mg Fe/Kg as ferrous sulfate monohydrate (FeSO4·H2O) and returned to normal diet one day later, Tested on days 1, 3, 7, 14, and 21 after the end of the iron addition. The results showed that the liver morphology was normal in the group C. The groups E1 and E2 showed the structure destroyed of hepatic lobules, the disordered of hepatic cords, the reduction of the central veins and the presence of erythrocytes accompanied by inflammatory cell infiltration. The group E2 showed more serious damage than the group E1, but these phenomena will largely return to normal on day 21. The perls staining showed that large deposits of iron-containing hemosiderin in the hepatic sinus after iron overdose intake, and the changes of iron deposition and pathological damage had certain regularity in time. The expression of Bax, Caspase-3, Caspase-8, and Caspase-9 in groups E1 and E2 were increased from days 1 to 21, which was in contrast to the Bcl-2, and it has a dose dependent. This suggested that iron overdose triggered apoptosis, which was supported by our ultrastructural observations of chromatin marginalization and impaired mitochondrial swelling. In addition, the expression of PI3K and AKT were significantly increased in the iron overdose groups, while the expression of mTOR was decreased. Above all, iron overdose can induce apoptosis in chicken hepatocytes through regulation of the PI3K/AKT/mTOR axis, leading to pathological damage. The type of iron overdose-induced damage was dose-dependent but not permanent. These results provide a theoretical basis for a comprehensive understanding of the importance of mineral nutrition management in poultry and the possible risk of excessive iron intake.

Reticuloendothelial virus (REV) is widely found in many domestic poultry areas and results in severe immunosuppression of infected chickens. This increases the susceptibility to other pathogens, which causes economic losses to the poultry industry. The aim of our study was to determine whether polyinosinic-polycytidylic acid [Poly (I: C)] treatment could inhibit REV replication in chicken macrophage-like cell line, HD11. We found that Poly (I: C) treatment could markedly inhibit REV replication in HD11 from 24 to 48 h post infection (hpi). Additionally, Poly (I: C) treatment could switch HD11 from an inactive type into M1-like polarization from 24 to 48 hpi. Furthermore, Poly (I: C) treatment promoted interferon-β secretion from HD11 post REV infection. Moreover, Toll-like receptor-3 (TLR-3) mRNA and protein levels in HD11 treated with Poly (I: C) were markedly increased compared to those of HD11 not treated with Poly (I: C). The above results suggested that Poly (I: C) treatment switches HD11 into M1-like polarization to secret more interferon-β and activate TLR-3 signaling, which contributes to block REV replication. Our findings provide a theoretical reference for further studying the underlying pathogenic mechanism of REV and Poly (I: C) as a potential therapeutic intervention against REV infection.

Iron is a mineral that the body acquires from the environment in order to maintain physiological function; however, excessive iron causes disease. The aim of this work is to investigate the processes by which excessive iron in diets induces kidney fibrosis in sheep by disorders their inflammatory factors. All sheep were fed a basal diet supplemented with 50 (CON), 500 (L-iron), 1000 (M-iron), and 1500 (H-iron) mg Fe/kg as ferrous sulfate monohydrate (FeSO4·H2O), respectively. Hematoxylin-Eosin (H&E), Perls, and Masson staining were used to observe histopatholological alterations; Western blotting, ELISA, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect changes in the amounts of key inflammatory factor genes and proteins. As iron intake rose, glomerular cell contents dropped, tubular inflammatory cells infiltrated and fibrin was secreted, collagen fiber deposition and fibrosis have noticeable symptoms. Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) activities were decreased, while interleukin-2 (IL-2), interleukin-6 (IL-6), nuclear factor-κB (NF-κB), and transforming growth factor-β1 (TGF-β1) actvities were increased. Excessive iron disorders inflammatory factor secretion, triggers an inflammatory response, and promotes the development of renal fibrosis, according to this study.

Background Reticuloendotheliosis virus (REV) is a retrovirus that causes severe immunosuppression in poultry. Animals grow slowly under conditions of oxidative stress. In addition, long-term oxidative stress can impair immune function, as well as accelerate aging and death. This study aimed to elucidate the pathogenesis of REV from the perspective of changes in oxidative-antioxidative function following REV infection. Methods A total of 80 one-day-old specific pathogen free (SPF) chickens were randomly divided into a control group (Group C) and an REV-infected group (Group I). The chickens in Group I received intraperitoneal injections of REV with 104.62/0.1 mL TCID50. Thymus was collected on day 1, 3, 7, 14, 21, 28, 35, and 49 for histopathology and assessed the status of oxidative stress. Results In chickens infected with REV, the levels of H2O2 and MDA in the thymus increased, the levels of TAC, SOD, CAT, and GPx1 decreased, and there was a reduction in CAT and Gpx1 mRNA expression compared with the control group. The thymus index was also significantly reduced. Morphological analysis showed that REV infection caused an increase in the thymic reticular endothelial cells, inflammatory cell infiltration, mitochondrial swelling, and nuclear damage. Conclusions These results indicate that an increase in oxidative stress enhanced lipid peroxidation, markedly decreased antioxidant function, caused thymus atrophy, and immunosuppression in REV-infected chickens.

The aim of this work is to investigate the relationship between iron and oxidative stress in the immune organs of excessive iron-fed sheep. Sixteen German Mutton Merino rams were randomly divided into 4 groups, which were fed the basal diets supplemented with 50 (CON), 500 (L-iron), 1000 (M-iron), and 1500 (H-iron) mg Fe/kg as ferrous sulfate monohydrate (FeSO4·H2O), respectively. The actual iron content in the diet was determined to be 457.68 (CON), 816.42 (L-iron), 1256.78 (M-iron), and 1725.63 (H-iron) mg/kg, respectively. The consequences of oxidative damage were tested in 4 groups. The results showed that the contents of malondialdehyde (MDA), nitric oxide (NO), hydrogen peroxide (H2O2), and the activity of nitric oxide synthase (iNOS) were increased in excessive iron-fed sheep. Moreover, the present results revealed that excess iron was associated with a significant decrease in the activities of antioxidant capacity, such as glutathione peroxidase (GPx) activity and total antioxidant capacity (T-AOC) levels. The iNOS mRNA expression declined in excessive iron-fed sheep, indicating that down-regulation is likely to occur at the transcription level, which is consistent with the studies of iron blockades iNOS transcription. Surprisingly, the activity of glutathione peroxidase 1 (GPx1) continued to decline, but the expression levels of GPX1 mRNA and protein increased first and then decreased. This suggests that at the transcriptional and translation levels, the body compensatively increases the amount of GPx1 to maintain the balance of the oxidation-antioxidant system to resist peroxidation. Hematoxylin-eosin (HE) staining revealed histopathological changes in immune organs, such as lymphocyte infiltration and cell death, indicating that excessive iron-induced oxidative damage indirectly affects the body's immune function. These findings confirm the role of iron in regulating the homeostasis of the oxidation-antioxidant system.

Reticuloendotheliosis virus (REV), an avian retrovirus is able to infect a variety of birds and can cause immunosuppression. The aim of this study was to investigate the relationship of thymic lymphocytes apoptosis, proliferation and T cell subtype with immunosuppression. In this study, a hundred and twenty one-day old SPF chickens were randomly divided into control groups (group C) and a REV infection groups (group I). The chickens of group I received intraperitoneal injections of REV with 104.62/0.1 ml TCID50. On day 14, 21, 28 and 35 post-inoculation, the chickens of C group and I group were sacrificed by cardiac puncture blood collection, and the thymic lymphocytes was sterile collected. The proliferation ability of lymphocytes was tested by Cell Counting Kit-8. Flow cytometry was performed to detect apoptosis, cell cycle stage and the change in T cell subtype. The RNA genome copy numbers of REV virus were detected using real-time PCR. Real-time PCR and western blotting were performed to analyze the expression of CyclinD1 and Bcl-2. Our results showed that REV genome copy number steadily declined, the proliferation potential of thymic lymphocytes was inhibited, lymphocytes apoptosed, the ratio of CD4+/CD8+ decreased and the expression of CyclinD1 and Bcl-2 were firstly inhibited, then rapidly recovered. Thus, immunosuppression lead by REV is closely related to the change of T cell subtype, apoptosis, and proliferation of thymic lymphocytes.

The purpose of this study was to evaluate the effects and mechanism of Lactobacillus on ameliorating ulcerative colitis chicks induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). There are three groups in this study, control, Lactobacillus and ulcerative colitis groups. 1-day-old chicks were fed with microcapsules containing Lactobacillus LA-5 daily for Lactobacillus group and clustered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to make the model of ulcerative colitis at ten-day-old. Chicks in control and ulcerative colitis groups were fed with empty microcapsules daily at 1-day-old and then chicks in ulcerative colitis group were induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) for preparation of ulcerative colitis model at 10-day-old. We detected the changes of mRNA and protein expression of TNF-α and IL-10 in the colon by Real-Time PCR and Western Blot. Histopathology evaluation on colon was conducted. Results showed that chicks pretreated with Lactobacillus had striking injury improvement compared with ulcerative colitis group in histopathology. Compared with ulcerative colitis group, down-regulation of TNF-α and up-regulation of IL-10 were observed in Lactobacillus group chicks. Therefore, Lactobacillus could improve the injury of intestinal mucosa and reduce inflammatory response by regulating mRNA and protein expression levels of TNF-α and IL-10, respectively. In conclusion, Lactobacillus could ameliorate the effects on chicks of TNBS-induced ulcerative colitis by reducing the inflammation and regulating the expression of TNF-α and IL-10, respectively.

Background: Iron plays a key role in biological metabolism as an essential microelement. Excess iron may cause pathological damage to the body. The purpose of this work is to explore the disorders of major inflammatory factors and histopathological lesions in the liver of excess-iron-fed sheep. Twenty German Mutton Merino sheep were randomly divided into 4 groups, control group (CON), iron-excess group one (IronE1), iron-excess group two (IronE2) and iron-excess group three (IronE3), respectively. Each group was fed with basal diets supplemented with 50 (CON), 500 (IronE1), 1000 (IronE2), and 1500 (IronE3) mg/kg as ferrous sulfate monohydrate (FeSO4 ·H2O). After 75 days, the liver was removed and collected. A variety of methods were utilized to detect indicators of sheep liver. Results: The histopathological damage of liver in sheep was rather severe with the excess of iron. Hemosiderin deposits were also obviously discovered. The results also showed that the expression of both protein and mRNA of IL-1β, TNF-α and IFN-γ reduced, but the factors of IL-2, IL-6, NF-κB and TGF-β1 obviously increased in the liver of each iron excess group. Corresponding changes were also discovered with the addition of iron dosage. The content of inflammatory factors above showed a significant change with an addition of 1500 mg/kg iron into the basic diet, which indicated that excess iron inhibited the release of IL-1β, TNF-α and IFN-γ in the sheep liver. The inflammation caused by excess iron extenuated by reducing the content of these three pro-inflammatory factors. The expression of IL-2, IL-6, NF-κB and TGF-β1 increased. As pro-inflammatory factors induced inflammation, anti-inflammatory factors also increased to protect the body from tissue damage. Conclusions: It can be concluded that excess iron can change the expression of main inflammatory factors in sheep liver, which will be an instructive significance to the development of medical prospect for sheep breeding and disease diagnosis.

PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability. However, the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement. Here, we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone. The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine. The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes, including antigen-processing and antigen-presenting genes, were upregulated, whereas the promoter demethylation was downregulated after decitabine exposure. Therefore, decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade. The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses, which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.

Haemophilus parasuis is an important pathogen causing severe infections in pigs. However, the specific bacterial factors that participate in pathogenic process are poorly understood. VacJ protein is a recently discovered outer membrane lipoprotein that relates to virulence in several pathogens. To characterize the function of the vacJ gene in H. parasuis virulent strain HS49, a vacJ gene-deletion mutant ΔvacJ and its complemented strain were constructed. Our findings supported that VacJ is essential for maintenance of cellular integrity and stress tolerance of H. parasuis, by the demonstrations that the ΔvacJ mutant showed morphological change, increased NPN fluorescence and, and decreased resistance to SDS-EDTA, osmotic and oxidation pressure. The increased susceptibility to several antibiotics in the ΔvacJ mutant further suggested that the stability of the outer membrane was impaired as a result of the mutation in the vacJ gene. Compared to the wild-type strain, the ΔvacJ mutant strain caused a decreased survival ratio from the serum and complement killing, and exhibited a significant decrease ability to adhere to and invade PK-15 cell. In addition, the ΔvacJ mutant showed reduced biofilm formation compared to the wild-type strain. Furthermore, the ΔvacJ was attenuated in a murine (Balb/C) model of infection and its LD50 value was approximately fifteen-fold higher than that of the wild-type or complementation strain. The data obtained in this study indicate that vacJ plays an essential role in maintaining outer membrane integrity, stress tolerance, biofilm formation, serum resistance, and adherence to and invasion of host cells related to H. parasuis and further suggest a putative role of VacJ lipoprotein in virulence regulation.

PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability. However, the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement. Here, we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone. The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine. The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes, including antigen-processing and antigen-presenting genes, were upregulated, whereas the promoter demethylation was downregulated after decitabine exposure. Therefore, decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade. The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses, which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.

Reticuloendotheliosis virus (REV) is an avian retrovirus that causes immunosuppression, growth retardation, and oncogenesis in a variety of birds. REV infection is epidemic in many countries. In this study, we used high-throughput sequencing to identify microRNAs (miRNAs) associated with REV infection. A total of 88 differentially expressed miRNAs were identified in samples collected on days 21 and 28 post-REV infection. Possible target genes of the differentially expressed miRNAs were analyzed. We observed that expression of proapoptotic, proto-oncogene, and carcinogenic cytokine mRNAs was highly upregulated, whereas expression of antiapoptotic cytokine mRNAs was significantly downregulated. Our findings provide a potential link between miRNA expression and the pathogenesis of REV infection.

Graphite deposit is important ore in Huili County, Sichuan Province. It is located in the middle part of the Kangdian axis and the middle part of the Kangdian basement fault uplift zone. The graphite deposit is located in the strata of the Dayingshan Formation of the Lower Proterozoic Hekou Group. The deposit belongs to sedimentary metamorphic graphite deposit formed under the dual factors of regional and thermal contact metamorphism. The ore body is strictly controlled by horizons. Graphite is composed of migmatized graphite quartz schist ore and migmatized graphite schist ore. The former is of the main type and the latter to the second type. Through comparative analysis of metallogenic geological and geophysical characteristics, it is considered that the gold rain graphite deposit is influenced by strata, structure, magmatic rocks, metamorphism, migmatization and other factors.

Objective The aim of this study was to evaluate the value of contrast-enhanced ultrasound (CEUS) for blood perfusion of primary liver cancer (PHC) and investigate the correlation between microvascular architecture of PHC and pathological differentiation.

Tangjiashan landslide is a typical highspeed consequent landslide of medium-steep dip angle. This landslide triggered by earthquake took place in about semi-minute. The relative sliding displacement is 900 meters, so average sliding speed is about 30 meters per second. The longitudinal length of barrier dam which is formed by high-speed landslide along river is 803.4 meters; and maximum width crossing river is 611.8 meters. And its volume is estimated about 20.37 million steres. Through detailed geological investigation of the barrier dam, together with early geological information before earthquake, geological structures of the barrier dam and its stability of upstream and downstream slopes are studied when water level reaches different elevations in condition of continual after shocks with seismic intensity of 7 or 8 Richter scale. On this basis, dam-breaking mode of barrier dam is discussed deeply. Thereby, analytic results provide significant guidance and advices to front headquarters of Tangjiashan barrier dam, so that some proper engineering measures can be implemented and flood discharge can be carried out well.

Background Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine. Recently, the outbreak of the epidemic disease has been a serious problem in swine industry. The objective of this study is to develop a rapid, sensitive, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea virus (PEDV) in less equipped laboratories. Results The optimal reaction condition of the current real-time RT-LAMP for PEDV was 62 °C for 45 min. It was capable of detecting PEDV from clinical samples and differentiating PEDV from several related porcine viruses, while it did not require additional expensive equipment. The minimum detection limit of the real-time RT-LAMP assay was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold more sensitive than that of one-step RT-PCR. By screening a panel of clinical specimens, the results showed that this method presented a similar sensitivity with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in detection of clinical samples. Conclusions In this study, we have developed a new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect PEDV.This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies.

In the face of the impact of the Internet tide, more and more traditional large-scale retail enterprises have used e-commerce platform for transformation. On the basis of analyzing the advantages, disadvantages and business model innovation forms of the traditional large-scale retail enterprises' transition to the e-commerce, this paper puts forward some strategic suggestions about how to transform into e-commerce for the traditional large-scale retail enterprises. In addition, a case study of the innovative transition way of Wal-Mart's e-commerce is analyzed. The paper is hoping to provide a reference to the transition into e-commerce model for traditional large-scale retail enterprises.

Jida 4 is an overseas ultra-deep prospecting well completed by CNPC for important scientific research, with design depth of 6350m and completion depth of 6596m. Three formation pressures and drillability profiles of rocks are established by investigation to achieve optimized and fast drilling technology, including optimization of well bore structure, bit and drilling tool combination and improvement of drilling parameters; the developed salt-resistant and high-temperature resistant ultra-high density saturated salt water drilling fluid system may ensure indoor experimental density of 2.55g/cm1, temperature of 180°C, the highest in-situ density of 2.44g/cm3 and temperature of 163°C and safely drill 450m interval of KKC layer, so as to achieve hole cleaning and downhole safety; research and application of ultra-high density salt-resistant and high-temperature resistant slurry system and spacer fluid system may ensure slurry density of 2.48g/cm3 and spacer fluid density of 2.5g/cm3, so as to achieve safe cementing of deep well.

CYP 2C8, which carries out the oxidative metabolism of at least 5% of clinical drugs, has attracted increasing attention in recent years. New drugs (substances), inducers and inhibitors of CYP 2C8 have been developed and the drug metabolism has been investigated to understand the clinical role of CYP2C8. The cases of CYP2C8 genetic polymorphisms linked to diseases have increased and have been investigated. Herein, important progress in these areas has been reviewed with an emphasis on drug metabolism. Polymorphisms, diseases related to CYP2C8, some important drugs (substances) and inhibitors are reviewed and discussed.

100 chicks were randomly divided into probiotics group(P group), Newcastle disease (ND) vaccine group(V group), probiotics ND vaccine group (P+V group)and normal group(N group). The dynamic changes of T lymphocytes number in the cecal tonsil, gland of Harder, and Peyer's patch of duodenum and ileum of probiotics chicks vaccinated with ND vaccine at 0,7,14,28 and 42 days post ND vaccine vaccination were determined by using paraffin section and acid nonspecifica-naphthyl acetate esterase (ANAE) staining method. The results showed that numbers of T lymphocytes in above immune tissue of P+V group and V group chicks was significantly enhanced compared with N and P group at 14 day after ND vaccine vaccination. The number of T lymphocytes in the cecal tonsil, gland of Harder, and Peyer's patch of duodenum and ileum of probiotics chicks vaccinated with ND vaccine was increased different degrees of more than ND alone vaccination chicks. The number of T lymphocytes in above immune tissues of chicks alone utilized with probiotics was heightened than normal chicks. These results indicate that probiotics can enhance the cellular immune function in gastrointestinal and respiratory local mucosa of chicks and the cellular immune response against ND vaccine.

Based on the research results related to product over-functions, interviewing with business and consumer, to build in line with our business and market characteristics of the product over-functions incentive model. Mobile phone manufacturers as the main survey, conducted a questionnaire survey, based on regression analysis using SPSS to test the model results showwing that: to promote sales contribution to the greatest excess, followed by the design preferences, once again is the information asymmetry, while the Chinese consumer market `s face consumption is also a significant impact.

The differences between mouse mAβ(1-42) and human hAβ(1-42), explored using CD and fluorescence spectroscopy, transmission electron microscopy, ROS fluorescent assay, and neuronal cell viability, revealed that mAβ(1-42) as a three-site mutant (R5G, Y10F and H13R) of hAβ(1-42) altered the metal (copper and zinc) binding sites, reduced the proneness to form β-sheet structures and aggregated fibrils, alleviated the generation of ROS, and decreased the cytotoxicity, in contrast to hAβ(1-42).

In the title molecule, C5H6BrN3, the pyrimidine ring is essentially planar, with an r.m.s. deviation of 0.007 Å. The Br and N atoms substituted to the pyrimidine ring are coplanar with the ring [displacements = 0.032 (1) and 0.009 (5) Å, respectively], while the methyl C atom lies 0.100 (15) Å from this plane with a dihedral angle between the pyrimidine ring and the methylamine group of 4.5 (3)°. In the crystal, C—H...N, C—H...Br and N—H...N hydrogen bonds link the molecules into a two-dimensional network in the (011) plane.