Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells

Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.

Genetic Study on JS399-19 Resistance in Hyphal Fusion of Fusarium graminearum by Using Nitrate Nonutilizing Mutants as Genetic Markers

Twenty-two nitrate nonutilizing （nit） mutants were recovered from five wild-type isolates of Fusarium graminearum and fifty nit mutants were recovered from three JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some biological properties were compared between nit mutants and their parental isolates. The results showed that there were no significant differences in growth rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants and their parental isolates. But the conidial production and the sexual reproduction ability changed to some extent. There was no cross resistance toward chlorate and JS399-19 in F. graminearum and the resistance could be stable through 20-time subcultures. Therefore, the nit could be used as a genetic marker for studying the genetics of JS399-19 resistance in E graminearum, which was used to study JS399-19 resistance transferability in hyphal fusion. Resistance in JS399-19 could not be transferred by hyphal fusion or could be transferred with low chance between two compatible isolates, which would delay the development of JS399-19 resistance in the field.

Children with Steroid-resistant Nephrotic Syndrome:Long-term Outcomes of Sequential Steroid Therapy

Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. Methods We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. Results Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five （55.6%） achieved complete or partial remission, 19 （30.2%） of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children （77.8%） experienced relapses, of whom 31 （49.2%） demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients （7.9%） complained of vomiting or nausea during MPT infusion; 25 （39.7%） experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 （41.3%） had poor growth associated with long-term steroid use. Twenty-eight patients （44.4%） failed to respond to MPT, of whom 21 （33.3%） achieved complete or partial remission with immunosuppressive agents. Conclusion MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.

Severe ulcerative colitis: At what point should we define resistance to steroids?

Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.

Steroid resistance in leukemia

There are several types of leukemia which are characterized by the abnormal growth of cells from the myeloid or lymphoid lineage. Because of their lympholytic actions, glucocorticoids(GCs) are included in many therapeutic regimens for the treatment of various forms of leukemia. Although a significant number of acute lymphoblastic leukemia patients respond well to GC treatment during initial phases; prolonged treatments sometimes results in steroid-resistance. The exact mechanism of this resistance has yet not been completely elucidated, but a correlation between functional GC receptor expression levels and steroidresistance in patients has been found. In recent years, several other mechanisms of action have been reported that could play an important role in the development of such drug resistances in leukemia. Therefore, a better understanding of how leukemic patients develop drug resistance should result in drugs designed appropriately to treat these patients.

Activity of the Fungicide JS399-19 Against Fusarium Head Blight of Wheat and the Risk of Resistance

This report reviews the characteristics of JS399-19, a novel cyanoacrylate fungicide. JS399-19 strongly inhibits the mycelial growth of the fungal plant pathogens of the genus Fusarium and exhibits great potential in controlling Fusarium head blight （FHB） on wheat and other cereals. The mode of action of JS399-19 is evidently different from that of benzimidazole （for example, carbendazim） and other sort of fungicides, making it a possible replacement for carbendazim in China to manage carbendazim-resistant subpopulations of Fusarium graminearum and F. asiaticum. JS399-t9 has excellent protective and curative activity against these pathogens. Incorrect use of this fungicide, however, is likely to select for resistance. Among JS399-19-resistant mutants of F. asiaticum induced in the laboratory, the resistant level of mutants was high and the phenotype of resistance against JS399-19 was conferred by a major gene by genetic analysis. The fitness of laboratory-induced JS399-19-resistant mutants of F. asiaticum was nearly equal to that of their parents. JS399-19 lacks cross resistance with other sort fungicides. To control FHB with JS399-19 and to delay the development of the fungicide-resistance, farmers should use tank mixtures containing JS399-19 and carbendazim, metconazole, tebuconazole, or prothioconazole.

Structure of Micro-nano WC-10Co4Cr Coating and Cavitation Erosion Resistance in NaCl Solution

Cavitation erosion （CE） is the predominant cause for the failure of overflow components in fluid machinery. Advanced coatings have provided an effective solution to cavitation erosion due to the rapid development of surface engineering techniques. However, the influence of coating structures on CE resistance has not been sys- tematically studied. To better understand their relationship, micro-nano and conventional WC-10Co4Cr cermet coat- ings are deposited by high velocity oxygen fuel spray- ing（HVOF）, and their microstructures are analyzed by OM, SEM and XRD. Meanwhile, characterizations of mechan- ical and electrochemical properties of the coatings are carried out, as well as the coatings＇ resistance to CE in 3.5 wt % NaC1 solution, and the cavitation mechanisms are explored. Results show that micro-nano WC-10Co4Cr coating possesses dense microstructure, excellent mechanical and electrochemical properties, with very low porosity of 0.26 4-0.07% and extraordinary fracture toughness of 5.58 4-0.51 MPa.m1/2. Moreover, the CE resistance of micro-nano coating is enhanced above 50% than conventional coating at the steady CE period in 3.5 wt % NaC1 solution. The superior CE resistance of micro- nano WC-10Co4Cr coating may originate from the unique micro-nano structure and properties, which can effectively obstruct the formation and propagation of CE crack. Thus,a new method is proposed to enhance the CE resistance of WC-10Co4Cr coating by manipulating the microstructure.

Influence of rare earth elements on corrosion resistance of BFe10-1-1 alloys in flowing marine water

The corrosion behavior of BFe10-1-1 alloy with different rare earth （RE） contents in simulated flowing marine water was investigated by X-ray diffractometer and scanning electron microscope （SEM）. It was demonstrated that the corrosion rate of BFel0-1-1 alloy with the same chemical compositions in faster flow velocity of marine water was higher than that in a lower flow velocity of marine water. Fixing the flow velocity, BFe 10-1-1 alloy had the best flushing corrosion resistance when the RE content was 0.04wt.%. The consequence of such good corrosion resistance was attributed to the formation of compact protective film on alloy surface containing RE phase such as CeNis. The RE-contained film combines with other corrosion products firmly, which was difficult to fall off from the alloy surface in the flowing marine water. Additionally, SEM analysis confirmed that pitting mechanism, which would be transformed to spalling mechanism gradually with further increasing RE content, was the prevalent mechanism when the alloy contained 0.04wt.%RE.

Characterization and functional analysis of β-1,3-galactosyltransferase involved in Cry1Ac resistance from Helicoverpa armigera(Hübner)

Carbohydrate chains are the principal antigens by which Bacillus thuringiensis（Bt） identify receptor proteins. The interaction between the antigen and Bt causes a pore in the membrane of midgut epithelial cells of insects. Receptor proteins, such as aminopeptidase N and alkaline phosphatase, are glycoproteins. Cadherin is another cell surface receptor protein which has potential glycosylation sites. Glycosyltransferase is very important for the synthesis and modification of receptor proteins. It can indirectly influence the function of Bt. The 1 950 bp full-length c DNA encoding β-1,3-galactosyltransferase was cloned from the the midgut of Helicoverpa armigera by degenerative PCR combined with RACE techniques（GAL-Harm, Gen Bank accession no.： GQ904195.1） with two potential N-glycosylation sites（^157NNTI^160 and ^272NKTL^275）. Protein sequence alignments revealed that H. armigera β-1,3-galactosyltransferase shared high identity with β-1,3-galactosyltransferase in other insect species. The expression level of the β-1,3-galactosyltransferase gene in Cry1Ac-resistant H. armigera larvae was 9.2-fold higher than that in susceptible strain. The function of β-1,3-galactosyltransferase was investigated using RNAi technique. The result showed Cry1 Ac enhanced the toxicity against the si RNA-treated larvae compared with non-si RNA-treated ones, which indicated β-1,3-galactosyltransferase played an important role for the insecticidal toxicity of Cry1 Ac in H. armigera.

The Clinical Efficacy of Low-Dose Tacrolimus Combined with Tripterygium to Treat the Steroid-Resistant Nephrotic Syndrome

Objective: To observe the clinical efficacy and safety of low dose tacrolimus (TAC) combined with tripterygium (TW) in treatment of steroid resistant nephritic syndrome (SRNS). Method: The patients, who were diagnosed with mesangial proliferative glomerulonephritis (MesPGN) and focal segmental glomerulosclerosis (FSGS) by biopsy and failed to respond to a 3-month treatment with prednisone (1 mg/kg·d), were randomly divided into 2 groups (TAC + TW Group and TW Group). Initially TAC + TW group took TAC 0.05mg/(kg·d) 2 h after meal at 12 h interval. The plasma TAC level was examined after 3 days and was kept at 1.5 - 4 ng·ml;meanwhile, TW was given at 60 mg/d before meal. TW group only took TW (60 mg/d). The efficacy, adverse reactions and plasma TAC levels were observed in each group. Results: 1) Totally 20 SRNS patients completed the trial, 11 of TAC + TW Group and 9 of TW Group. There is no statistical difference between the two groups in terms of age, gender, duration since onset of the disease, blood pressure, 24 h UPQ, serum albumin, creatinine, cholesterol, triglyceride, FBG, kidney pathological categories, time of taking prednisone etc.;2) Urine protein started to decrease after 1 month treatment in both of TAC + TW and TW groups. By the 12th month of treatment, TAC + TW group showed 8 cases of complete remission (72.7%), 2 cases of partial remission (18.2%) and 1 case of no improvement (9.1%), while those of TW groups were 2 (22.2%), 4 (44.5%) and 3 (33.3%), respectively;3) With treatment, the TAC + TW Group patients’ plasma protein was significantly higher than that of pretreatment stage and recovered to normal level after 6 month of treatment. However, there was no significant plasma protein increase in TW Group. No obvious changes were observed on serum creatinine level of patients of both the two groups;4) The incidence of adverse reactions was not significantly different between the two groups. Conclusion: TAC + TW reduced proteinuria of SRNS patients, increased clinical remission rate and was tolerant to SRNS patients. We conclude that TAC + TW treatment is an effective way to treat patients with SRNS.

Effect of Fused MgO-ZrO_2 Clinker Addition on Thermal Shock Resistance of MgO-ZrO_2 Unfired Bricks

MgO -ZrO2 unfired bricks with ZrO2 content up to 8% at the interval of 2% were prepared, using fused magnesia （ MgO ： 97% ） and fused MgO - ZrO2 clinker （ ZrO2 ： 14. 33% ） as starting materials and phenolic resin as binder. The effects of ZrO2 content on thermal shock resistance （TSR） and other properties such as cold and hot modulus of rupture have been investigated. Re- sidual cold modulus of rupture ratio after heating at 1 000 ℃ and quenching by air blowing was adopted to characterize TSR. Addition of the MgO -ZrO2 clinker improves TSR, attributing to the microcrack toughening effect by thermal expansion mismatch between different phases. When ZrO2 content goes above 4%. the impro- ving effect tends to be moderate. The introduction of MgO- ZrO2 clinker can also improve the HMOR at 1 500 ℃, while the increased ZrO2 content reduces CMOR of the bricks prefired at 1 600 ℃, due to the thermal expansion mismatch effect. Compromising the overall properties, the optimal ZrO2 content for such magnesia based unfired brick is suggested to be 4%.

Antimicrobial Resistance,Virulence Profile,and Molecular Characterization of Listeria monocytogenes Isolated from Ready-to-eat Food in China,2013-2014

We aimed to investigate the potential pathogenic profile and antibiotic resistance of Listeria monocytogenes isolated from ready-to-eat food in China.Antimicrobial resistance was determined by broth microdilution following the Clinical and Laboratory Standards Institute protocol Molecular serotyping,virulence,and resistance genes were identified using PCR.Multi-locus

NPHS2 Gene Mutation and Polymorphisms in Indonesian Children with Steroid-Resistant Nephrotic Syndrome

Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalities or variants appeared?to be influenced by race and ethnic group. We have investigated?probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children?with primary SRNS?whovisited?the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were?conducted through screenings?for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing.?Fisher’s Exact Test was used to determine?the?correlation?between?NPHS2 polymorphisms and clinical manifestations.Results:?Seven?females (25%) and 21 males (75%)?participated in the study.?The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.?We identified 6 NPHS2polymorphisms,?i.e.?g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation?was found. There was?no correlation?between?NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The?results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.

Effect of CaO doping on corrosion resistance of Cu/(NiFe_2O_4-10NiO) cermet inert anode for aluminum electrolysis

The CaO-doped Cu/（NiFe2O4-10NiO） cermet inert anodes were prepared by the cold isostatie pressing-sintering process, and their corrosion resistance to Na3AlF6-K3AlF6-Al203 melt was studied. The results show that the relative density of 5Cu/（NiFe2O4-10NiO） cermet sintered at 1 200 ℃ increases from 82.83% to 97.63% when 2% CaO （mass fraction） is added. During the electrolysis, the relative density of cermet inert anode descends owing to the chemical dissolution of additive CaO at ceramic grain boundary, which accelerates the penetration of electrolyte. Thus, the corrosion resistance to melts of Cu/（NiFe2O4-10NiO） cermet inert anode is reduced. To improve the corrosion resistance of the cermet inert anode, the content of CaO doped should be decreased and the technology of cleaning the ceramic grain boundary should be applied.

Identification and Evaluation of Insect and Disease Resistance in Transgenic Cry1Ab13-1 and NPR1 Maize

PCR detection,quantitative real-time PCR(q-RTPCR),outdoor insect resistance,and disease resistance identification were carried out for the detection of genetic stability and disease resistance through generations(T2,T3,and T4)in transgenic maize germplasms(S3002 and 349)containing the bivalent genes(insect resistance gene Cry1Ab13-1 and disease resistance gene NPR1)and their corresponding wild type.Results indicated that the target genes Cry1Ab13-1 and NPR1 were successfully transferred into both germplasms through tested generations;q-PCR confirmed the expression of Cry1Ab13-1 and NPR1 genes in roots,stems,and leaves of tested maize plants.In addition,S3002 and 349 bivalent gene-transformed lines exhibited resistance to large leaf spots and corn borer in the field evaluation compared to the wild type.Our study confirmed that Cry1Ab13-1 and NPR1 bivalent genes enhanced the resistance against maize borer and large leaf spot disease and can stably inherit.These findings could be exploited for improving other cultivated maize varieties.

EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN HUMAN GASTRIC AND RENAL CARCINOMAS

Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression of MRP in the carcinoma tissues of 52 patients with gastric carcinoma and 20 cases with renal cell carcinoma. Results The positive expression rate of MRP was 38.5% (20/52) in gastric carcinoma tissues, and 60% (12/20) in renal carcinoma tissues. The expression of MRP both on cellular membrane and in cytoplasm was observed, but the expression in cytoplasm (thick granule) was more obvious. The positive expression rates of MRP in advanced gastric and renal carcinoma (Ⅲ orⅣ stage) were 60% (15/25) and 88.90% (8/9) reSPectively, which were higher than those in early lesion (Ⅰ or Ⅱ stage, 18.5% and 36.4% respectively). Furthermore, the patients with positive expression of MRP in gastric carcinoma tissues had shorter mean survival time and lower 5-year survival rate than that with negative eopression of MRP. Conclusion MRP plays an important role in the infiltration and metastasis of gastric and renal carcinoma and might contribute to the intrinsic drug - resistance in both carcinomas.

Effect of ZnO on Oxidation Resistance of Low Carbon MgO-C Refractories

Al-containing low carbon MgO - C refractories were prepared using 70% （in mass, the same hereinafter） fused magnesia （ ≤3 mm）, 24% fused magnesia powder （ 〈0. 074 mm） , 3% flake graphite, 3% Al powder and 4% phenolic resin （extra-added） as the basic formulation. Influence of ZnO addhion on oxidation resistance of the materials was investigated by adding 1% ZnO to substitute fused magnesia powder. The relationship between in-situ formed spinel and ZnO in the matrix was discussed by comparing apparent porosity, cold crushing strength, and phase evolution of the materials matrix. The oxidation resistances of the two materials were compared by observing the formed dense MgO layer between the decarburized layer and the original layer. The result shows that adding ZnO in MgO - C refractories accelerates the in-situ formation of ZnAl204 spinel and the formation of dense MgO layer, thus improves the oxidation resistance of the low carbon MgO - C refractories.

Corrosion Resistance of Heat-Treated NST 37-2 Steel in Hydrochloric Acid Solution

Corrosion of metal components constitutes a major challenge in many engineering systems, with appropriate design, proper material selection, and heat treatment as commonly used control strategies. In this study, the corrosion behaviour of heat-treated (annealed, normalised, hardened, and tempered) NST 37-2 steel in three concentrations (1.0, 1.5 and 2.0 M) of hydrochloric acid solution was investigated using weight loss and electrode-potential methods. Results showed that corrosion rate increased with increase in acid concentration. The decreasing order of corrosion resistance was Tempered > Annealed > Normalised > Hardened > Untreated. The surface pictures of the heat-treated and untreated samples showed uniform and pitting corrosion with the latter becoming more pronounced as concentration increased.

Chinese Standards on Refractories Refractory Products-Determination of Abrasion Resistance at Ambient Temperature GB/T 18301-2012

This standard specifies the terms and definitions, theory, apparatus, specimens, test procedures, calcu- lation results, apparatus check and test reports, etc. of abrasion resistance at ambient temperature of refractory products.

Histopathology Review of Idiopathic Steroid Resistant Nephrotic Syndrome and Outcome in Children in North-West of Iran

Introduction: There is currently little information in the literature on the spectrum of histopathologic patterns in children presenting with idiopathic steroid-resistant nephrotic syndrome (iSRNS) in Iran. We conducted to compare the histopathologic distribution of different subtypes’ glomerular morphologic patterns in iSRNS and the clinical and biochemical parameters at the time of diagnosis and outcome of patients after immunosuppressive therapy. Material and Methods: This cross sectional study was done in two hundred children, aged 1 - 15 years, who were diagnosed for iSRNS and no response to 4 weeks of standard prednisone therapy (60 mg/m2/day) referred to nephropathology Department of Emam Reza hospital between 2005 and 2013. Demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy reports. We discussed histopathologic diagnosis and outcome of iSRNS after initial therapy in patients separately. This study investigated prognostic effects of histopathologic pattern on outcome of iSRNS. Results: The study included 200 children with iSRNS: 141 (70.5%) were males and 59 (29.5%) females, with male-to-female ratio of 2.4:1. The mean age was 7.23 ± 4.37 years (range: 1 - 15 years). Upon pathologic investigation of iSRNS cases, focal segmental glomerulosclerosis (NOS subtype) was the first, with a highest prevalence at a rate of 102/200 (51%) and MGN was the last, at a rate of 7/200 (3.5%). Children with iSRNS secondary to MCD are more likely to achieve remission and have better long term prognostic value (P 0.00). Focal segmental glomerulosclerosis (FSGS) (Tip and Collapse subtypes) is more likely to have worse outcome in response to immunosuppressive therapy (P 0.04). Conclusions: This study defines the true spectrum of clinicohistopathology patterns underlying iSRNS in children in Northwest of Iran. Also this study shows that the response to cyclosporine can be correlated with the underlying histopathology patterns which have been earned by adequate renal biopsy.