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Food allergies are a leading cause of anaphylaxis, and allergen-specific immune responses in both the innate and the adaptive immune system play key roles in its pathogenesis. We conducted a comprehensive phenotypic and functional investigation of immune cell responses from nonallergic (NA) and peanut allergic (PA) participants cultured with media alone or peanut protein and found, surprisingly, that NK cell activation was strongly associated with the immune response to allergen in PA participants. Peanut-responsive NK cells manifested a distinct expression pattern in PA participants compared with NA participants. Allergen-activated NK cells expressed both Th2 and immune regulatory cytokines, hinting at a potential functional role in mediating and regulating the Th2 allergic response. Depletion of CD3+ T cells attenuated the response of NK cells to peanut-allergen stimulation, suggesting that peanut-responsive NK cells are T cell dependent. We also showed that oral immune therapy was associated with decreased NK responses to peanut allergen stimulation in vitro. These results demonstrate that NK cells are associated with the food-allergic immune response, and the magnitude of this mobilized cell population suggests that they play a functional role in allergic immunity. [ABSTRACT FROM AUTHOR]

In the Neurospora circadian system, the White Collar Complex (WCC) formed by WC-1 and WC-2 drives expression of the frequency (frq) gene whose product FRQ feedbacks to inhibit transcriptional activity of WCC. Phosphorylation of WCC has been extensively studied, but the extent and significance of other post-translational modifications (PTM) have been poorly studied. To this end, we used mass-spectrometry to study alkylation sites on WCC, resulting in discovery of nine acetylation sites. Mutagenesis analysis showed most of the acetylation events individually do not play important roles in period determination. Moreover, mutating all the lysines falling in either half of WC-1 or all the lysine residues in WC-2 to arginines did not abolish circadian rhythms. In addition, we also found nine mono-methylation sites on WC-1, but like acetylation, individual ablation of most of the monomethylation events did not result in a significant period change. Taken together, the data here suggest that acetylation or mono-methylation on WCC is not a determinant of the pace of the circadian feedback loop. The finding is consistent with a model in which repression of WCC’s circadian activity is mainly controlled by phosphorylation. Interestingly, light induced expression of some light-responsive genes has been modulated in certain wc-1 acetylation mutants, suggesting that WC-1 acetylation events differentially regulate light responses. [ABSTRACT FROM AUTHOR]

We study the electronic structure and transport properties of Dirac electrons along a channel created by an exchange field through the proximity of ferromagnets on a silicene sheet. The multiple total internal reflection induces localized states in the channel, which behaves like an electron waveguide. An effect of spin- and valley-filtering originating from the coupling between valley and spin degrees is predicted for such a structure. Interestingly, this feature can be tuned significantly by locally applying electric and exchange fields simultaneously. The parameter condition for observing fully spin- and valley-polarized current is obtained. These findings may be observable in todays' experimental technique and useful for spintronic and valleytronic applications based on silicene. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to investigate the possibility of screening for herbicide resistance in the early stage of rapes growth. [Methods] Eight treatments were set for a herbicide concentration experiment. [Results] Rape sprouts were highly sensitive to the herbicide glyphosate, and even a very low concentration of glyphosate solution (187 mg/L) was sufficient to kill most of the rape seedlings, while the genetically modified herbicide-tolerant rape could tolerate higher concentrations of the herbicide. Low concentrations of glyphosate could be used for screening at the sprout stage, and the results of herbicide-tolerance screening were consistent with PCR testing. [Conclusions] This study lays a technical and material foundation for accelerating the cultivation of new herbicide-resistant rape varieties suitable for rapeseed production areas in the lower reaches of the Yangtze River. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to provide a basis for the rapid identification of the drug spraying effect in early stage and the molecular mechanism of chemical hybridizing in Brassica napus L. [Methods] Quantitative RT-PCR analysis showed that ALS was constitutively expressed in various tissues of 096030, including flower buds, four floral organs(calyxes, petals, stamens and pistils), roots, stems and leaves. ALS was prominently expressed in leaves and was expressed weakly in the petals and stamens. The male sterility-inducing effects of tribenuron-methyl on such two Brassica napus L. varieties as Ningyou18 and 096030 were investigated. [Results] Plants were twice sprayed with 0.2 μg/ml tribenuron-methyl on leaves. The results showed that 8-10 ml of tribenuron-methyl was applied per plant for the first time at bolting stage with 1-2 mm flower buds on 15-20 cm inflorescence, and the second spray was performed with 8-10 ml of tribenuron-methyl per plant 10 d later. The results showed that the percentage of the full sterile plants reached 100%, which lasted for the whole flowering period, and the relative seed setting rate was only about 4%. Thus, this method could fullfill the requirement of hybrid seed production in field. The in-vivo enzyme activity of acetolactate synthase(ALS) was assayed using 2 mm buds collected 3 d after spray. The results showed that 0.2 μg/ml tribenuron-methyl inhibited ALS activity. The ALS activity of Ningyou 18(CK) and Ningyou 18(0.2 μg/ml) was 3.20 and 1.30 μmol/(mg·h), respectively, and the ALS activity of 096030(CK) and 096030(0.2 μg/ml) was 3.37 and 1.25 μmol/(mg·h), respectively. The relative enzyme activity of ALS in Ningyou18 and 096030 was 40.63% and 37.23%, respectively, both of which decreased significantly. [Conclusions] These results showed that the change of ALS activity may be used as an index for quickly identifying and predicting the chemical hybridizing effect of tribenuron-methyl. [ABSTRACT FROM AUTHOR]

Background: Recent reports have indicated that Helicobacter pylori (H. pylori) might have an effect on gastrointestinal flora; moreover, gastric commensual bacteria have been observed in the development of duodenal ulcer (DU). Aims: In our study, we aimed to evaluate the effect of H. pylori eradication on gastrointestinal flora in DU patients. Methods: A case-control study was performed at Jiangsu Shengze Hospital between December, 2013 and April, 2014. The patients received antibiotic eradication therapy if H. pylori testing was positive. At least four weeks after cessation of the eradication therapy, a repeat gastroscopy was performed to collect biopsies again in the same position. Gastric mucosa samples and feces specimens were collected to extract bacteria DNA and then to quantify by real-time polymerase chain reaction (PCR). Results: After the eradication of H. pylori, an increase of Lactobacillus group, Clostridium leptum subgroup, Enterobacteria and a decrease of Clostridium coccoides subgroup were found in the antrum. In the corpus, the number of bacteria in the Lactobacillus group was increased and the expression of Clostridium coccoides subgroup was significantly down-regulated. In the feces samples, only the number in the Lactobacillus group was increased. Moreover, the distribution was significantly different between female and the male patients. Conclusions: The presence of H. pylori in the stomach suppressed the colonization with Lactobacillus group, Clostridium leptum subgroup and Enterobacteria. Gender might affect the distribution and/or recolonization of the bacteria in DU patients. [ABSTRACT FROM AUTHOR]

In the Neurospora circadian system, the White Collar complex (WCC) of WC-1 and WC-2 drives transcription of the circadian pacemaker gene frequency (frq), whose gene product, FRQ, as a part of the FRQ-FRH complex (FFC), inhibits its own expression. The WCC is also the principal Neurospora photoreceptor; WCC-mediated light induction of frq resets the clock, and all acute light induction is triggered by WCC binding to promoters of light-induced genes. However, not all acutely light-induced genes are also clock regulated, and conversely, not all clock-regulated direct targets of WCC are light induced; the structural determinants governing the shift from WCC's dark circadian role to its light activation role are poorly described. We report that the DBD region (named for being defective in binding DNA), a basic region in WC-1 proximal to the DNA-binding zinc finger (ZnF) whose function was previously ascribed to nuclear localization, instead plays multiple essential roles assisting in DNA binding and mediating interactions with the FFC. DNA binding for light induction by the WCC requires only WC-2, whereas DNA binding for circadian functions requires WC-2 as well as the ZnF and DBD motif of WC-1. The data suggest a means by which alterations in the tertiary and quaternary structures of the WCC can lead to its distinct functions in the dark and in the light. [ABSTRACT FROM AUTHOR]

CRABS CLAW (CRC) is a member of the YABBYA transcription factor gene family that plays an important role in floral organ development of plants. This study aimed to further investigate the regulatory function of CRC transcription factor in the development of floral organs of rape (Brassica napus L.). A 580 bp fragment of CRC gene was cloned by RT-PCR from total RNA of buds of rape cultivar Ningyou No. 10 to construct an inverted repeated expression cassette of CRC gene using intermediate vector pHurricane. Firstly, CRC gene fragment was positively inserted into the 5' end of a spliceable intron and negatively inserted into the 3' end of the intron. Subsequently, CaMV35S promoter sequence and inverted repeated expression cassette of CRC gene were transferred into pUC18 multiple clone site of binary expression vector pCAMBIAI1390. The constructed interference expression vector was named pA6-CRCi, which was further confirmed by restriction enzyme digestion and sequencing. [ABSTRACT FROM AUTHOR]

Several studies have investigated the correlation between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and cancer prognosis, with inconsistent results. Therefore, a meta-analysis was conducted to identify the potential correlation after pooling data from eligible studies. PubMed/Medline, Web of Science and The Cochrane Library electronic databases were searched for eligible studies on the prognostic role of MALAT1 in cancer, from inception to January, 2015. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to summarize the effect. A total of 1,198 patients from 10 studies were included in the analysis. The results suggested that MALAT1 expression was significantly associated with overall survival (HR=2.07, 95% CI: 1.67-2.56), disease-free survival (HR=2.60, 95% CI: 1.69-4.00) and recurrence-free survival (HR=3.28, 95% CI: 1.52-7.09). MALAT1 was alsofound to be significantly associated with tumor size (P=0.013). Overall, MALAT1 expression may be considered as a potential prognostic factor for cancer patients. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence showed that miRNAs serve as modulators of human cancer, either as oncogene or tumor suppressors. Cisplatin resistance is the most common cause of chemotherapy failure in gastric cancer (GC). However, the roles of miRNAs in cisplatin resistance of GC remain largely unknown. The aim of the study was to identify a novel miRNA/gene pathway that regulates the sensitivity of GC cells to cisplatin. Methods: In this study, we chose miR-223 by qRT-PCR analysis, the most significantly up-regulated miRNA in GC, to investigate its formation of DDP-resistant phenotype of GC cells and possible molecular mechanisms. Results: We found that miR-223 was most significantly up-regulated miRNA in DDP-resistant GC cells compared with parental GC cells. Besides, its expression was also significantly up-regulated in GC tissues. FBXW7 was identified as the direct and functional target gene of miR-223. Overexpression of FBXW7 could mimic the effect of miR-223 down-regulation and silencing of FBXW7 could partially reverse the effect of miR-223 down-regulation on DDP resistance of DDP-resistant GC cells. Besides, miR-223 and FBXW7 could affect the G1/S transition of cell cycle by altering some certain cell cycle regulators. Furthermore, miR-223 was found to be significantly up-regulated in H. pylori infected tissues and cells, suggesting that H. pylori infection may lead to GC development and DDP resistance. Conclusions: Our findings revealed the roles of miR-223/FBXW7 signaling in the DDP resistance of GC cells and targeting it will be a potential strategic approach for reversing the DDP resistance in human GC. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China. Methods. A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 5417 individuals in Yangzhong city. Questionnaires and 13C-urea breath test for H. pylori infection were performed. Results. Among 5417 subjects who completed questionnaires and 13C-urea breath test, 3435 (63.41%) were H. pylori positive. The prevalence reached a peak at the age of 30-39 years (90.82%). There was significant difference between sexes and women had a higher infection rate than men. The prevalence of H. pylori infection was also associated with eating kipper food and fried food. No association between H. pylori prevalence and smoking or drinking was found. Compared to healthy individuals, people with dyspeptic diseases (peptic ulcer, gastroenteritis) presented a high prevalence of H. pylori infection. Using multivariate logistic regression analysis, age and history of peptic ulcer and gastroenteritis were the independent predictors for H. pylori infection. Conclusions. Yangzhong cityhad a high prevalence of H. pylori infection and was related to several risk factors. The underlying mechanisms are needed to be further investigated. [ABSTRACT FROM AUTHOR]

Matrix vesicles (MVs) involved in the initiation of mineralization by deposition of hydroxyapatite (HA) in their lumen are released by the budding of mineralizationcompetent cells during skeletogenesis and bone development. To identify additional mineralization-related proteins, MVs were isolated from non-stimulated and stimulated Saos-2 cells in culture via an ExoquickTM approach and the corresponding proteomes were identified and quantified with label-free quantitative proteome technology. The isolated MVs were confirmed by electron microscopy, alkaline phosphatase activity (ALP), biomarkers, and mineral formation analyses. Label-free quantitative proteome analysis revealed that 19 calcium binding proteins (CaBPs), including Grp94, calnexin, calreticulin, calmodulin, and S100A4/A10, were up-regulated in MVs of Saos-2 cells upon stimulation of mineralization. This result provides new clues to study the mechanism of the initiation of MV-mediated mineralization. [ABSTRACT FROM AUTHOR]

Surface recognition and penetration are critical steps in the infection cycle of many plant pathogenic fungi. In Magnaporthe oryzae, cAMP signaling is involved in surface recognition and pathogenesis. Deletion of the MAC1 adenylate cyclase gene affected appressorium formation and plant infection. In this study, we used the affinity purification approach to identify proteins that are associated with Mac1 in vivo. One of the Mac1-interacting proteins is the adenylate cyclase-associated protein named Cap1. CAP genes are well-conserved in phytopathogenic fungi but none of them have been functionally characterized. Deletion of CAP1 blocked the effects of a dominant RAS2 allele and resulted in defects in invasive growth and a reduced intracellular cAMP level. The Δcap1 mutant was defective in germ tube growth, appressorium formation, and formation of typical blast lesions. Cap1-GFP had an actin-like localization pattern, localizing to the apical regions in vegetative hyphae, at the periphery of developing appressoria, and in circular structures at the base of mature appressoria. Interestingly, Cap1, similar to LifeAct, did not localize to the apical regions in invasive hyphae, suggesting that the apical actin cytoskeleton differs between vegetative and invasive hyphae. Domain deletion analysis indicated that the proline-rich region P2 but not the actin-binding domain (AB) of Cap1ΔAB was responsible for its subcellular localization. Nevertheless, the AB domain of Cap1 must be important for its function because CAP1 only partially rescued the Δcap1 mutant. Furthermore, exogenous cAMP induced the formation of appressorium-like structures in non-germinated conidia in CAP1ΔAB transformants. This novel observation suggested that AB domain deletion may result in overstimulation of appressorium formation by cAMP treatment. Overall, our results indicated that CAP1 is important for the activation of adenylate cyclase, appressorium morphogenesis, and plant infection in M. oryzae. CAP1 may also play a role in feedback inhibition of Ras2 signaling when Pmk1 is activated. [ABSTRACT FROM AUTHOR]

The formation of appressoria, specialized plant penetration structures of Magnaporthe oryzae, is regulated by the MST11- MST7-PMK1 MAP kinase cascade. One of its downstream transcription factor, MST12, is important for penetration and invasive growth but dispensable for appressorium formation. To identify additional downstream targets that are regulated by Pmk1, in this study we performed phosphorylation assays with a protein microarray composed of 573 M. oryzae transcription factor (TF) genes. Three of the TF genes phosphorylated by Pmk1 in vitro were further analyzed by coimmunoprecipitation assays. One of them, MoSFL1, was found to interact with Pmk1 in vivo. Like other Sfl1 orthologs, the MoSfl1 protein has the HSF-like domain. When expressed in yeast, MoSFL1 functionally complemented the flocculation defects of the sfl1 mutant. In M. oryzae, deletion of MoSFl1 resulted in a significant reduction in virulence on rice and barley seedlings. Consistent with this observation, the Mosfl1 mutant was defective in invasive growth in penetration assays with rice leaf sheaths. In comparison with that of vegetative hyphae, the expression level of MoSFL1 was increased in appressoria and infected rice leaves. The Mosfl1 mutant also had increased sensitivity to elevated temperatures. In CM cultures of the Mosfl1 and pmk1 mutants grown at 30°C, the production of aerial hyphae and melanization were reduced but their growth rate was not altered. When assayed by qRT-PCR, the transcription levels of the MoHSP30 and MoHSP98 genes were reduced 10- and 3-fold, respectively, in the Mosfl1 mutant. SFL1 orthologs are conserved in filamentous ascomycetes but none of them have been functionally characterized in non-Saccharomycetales fungi. MoSfl1 has one putative MAPK docking site and three putative MAPK phosphorylation sites. Therefore, it may be functionally related to Pmk1 in the regulation of invasive growth and stress responses in M. oryzae. [ABSTRACT FROM AUTHOR]

Appressorium formation is a key step in the infection cycle of Magnaporthe oryzae. Mst12 is a transcription factor essential for appressorium penetration and invasive growth. In this study we used the affinity purification approach to identify proteins that physically associate with Mst12. One of the Mst12-interacting genes identified was MoMCM1, which encodes a MADS-box protein orthologous to yeast Mcm1. MoMcm1 interacted with both Mst12 and Mata-1 in yeast two-hybrid assays. Deletion of MoMCM1 resulted in the loss of male fertility and microconidium production. The Momcm1 mutant was defective in appressorium penetration and formed narrower invasive hyphae, which may be responsible for its reduced virulence. In transformants expressing MoMCM1-eGFP fusion, GFP signals were observed in the nucleus. We also generated the Momcm1 mst12 double mutant, which was defective in penetration and non-pathogenic. On hydrophilic surfaces, germ tubes produced by the double mutant were severely curved, and 20% of them formed appressoria. In contrast, the Momcm1 or mst12 mutant did not form appressoria on hydrophilic surfaces. These results suggest that MoMCM1 and MST12 have overlapping functions to suppress appressorium formation under non-conducive conditions. MoMcm1 may interact with Mst12 and MatA-1 to regulate germ tube identity and male fertility respectively. [ABSTRACT FROM AUTHOR]

Background: Paeonia sinjiangensis K.Y. Pan is a perennial herb belonging to the ranunculaceae family and it is one of the most important crude drugs in traditional Chinese medicine. In this article, Paeonia sinjiangensis K.Y. Pan rich in polysaccharide is used as an experimental material. Materials and Method: Study the effects of proportion, temperature, times and time taken for the extraction yield of polysaccharide through a single-factor exploration. Then, through an orthogonal experiment (L9 (3)4), it was investigated to get the best extraction conditions. Results: The results showed that the ratio of solvent to raw material, number of extractions and duration of extraction were the main variables that influenced the yields of extracts. The separation procedure of precipitation with alcohol and the purification from the removing proteins were deeply analyzed. Meanwhile the contents of polysaccharide were determined by anthrone colorimetry. Conclusion: The highest yield was obtained when the ratio of solvent to raw material, number of extractions, and duration of extraction were 8:1, 2, and 1.5 h, respectively. The content of soluble polysaccharide is 51.57%. [ABSTRACT FROM AUTHOR]

Background: It is reported that the plant Hyssopus cuspidatus Boriss from Xinjiang has great value. This article deals with the detailed pharmacognostic evaluation of the crude drug H. cuspidatus Boriss. Materials and Methods: The essential oil of H. cuspidatus Boriss from Xinjiang, China, was extracted by the method of hydrodistillation and the chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC-MS). Results: The yield of essential oil based on the dry weight of the plant was 0.6%(w/w). Fifty compounds accounting for 99.42% of the total oil were identified. The major components were oxygenated terpenes (66.33%), monoterpenes (26.14%), oxygenated sesquiterpenes (1.25%), and octane (1.85%). Conclusion: Oxygenated terpenes were the main group of the compounds. The physicochemical parameters presented in this article may be proposed as parameters to establish the authenticity of H. cuspidatus Boriss and can possibly aid pharmacognostic and taxonomic species identification. [ABSTRACT FROM AUTHOR]

A rapid, effective, binary reverse phase rapid resolution liquid chromatographic method has been developed for the determination of Paeoniflorin extracted from Paeonia sinjiang K. Y. Pan. with short run time. RRLC separation was achieved by using Agilent (Zorbas XDB-C18 4.6 mmx50 mm, 1.8 μm) column with mobile phase complosed of methanol and 0.05 mol/l potassium phosphate monobasic. Flow rate was at 1.0 ml/min. Retention time was at about 1.16 min. Recovery rate was 99.8% and relative standard deviation of three replicate samples tested was 1.8%. RRLC method has been applied to both in vitro studies of paeoniflorin formulation and drug estimation in biological samples. [ABSTRACT FROM AUTHOR]

Cyanide or metal cyanide contaminations have become serious environmental and food-health problems. A fungal mutant of Trichoderma koningii, TkA8, constructed by restriction enzyme-mediated integration, has been verified to have a high cyanide degradation ability in our previous study. In this study, the mutant cells were entrapped in sodium-alginate (Na-alginate) immobilization beads to degrade cyanide and ferrocyanide in a liquid mineral medium. The results showed that the fungus in immobilization beads consisting of 3% Na-alginate and 3% CaCl2 could degrade cyanide more efficiently than a nonimmobilized fungal culture. For maximum degradation efficiency, the optimal ratio of Na-alginate and wet fungal biomass was 20:1 (m/m) and the initial pH was 6.5. In comparison, cell immobilization took at least 3 and 8 days earlier, respectively, to completely degrade cyanide and ferrocyanide. In addition, we showed that the immobilized beads could be easily recovered from the medium and reused for up to 5 batches without significant losses of fungal remediation abilities. The results of this study provide a promising alternative method for the large-scale remediation of soil or water systems from cyanide contamination. [ABSTRACT FROM AUTHOR]

Myofibroblastic-activated hepatic stellate cells are the major source of the collagen I-rich extracellular matrix in liver fibrosis but also produce matrix metalloproteinases, which remodel this protein. We have investigated the role of collagen I proteolysis in both regulating proliferation and maintaining the activated myofibroblastic phenotype of stellate cells in vitro. Compared with stellate cells plated on normal collagen I, those plated on a collagenase-resistant form of collagen I (r/r collagen) had reduced thymidine incorporation and proliferating cell nuclear antigen expression but increased p21 expression. Collagen! was shown to be rendered resistant to matrix metalloproteinases by artificial cross-linking in vitro using tissue transglutaminase exerted similar antiproliferative effects on stellate cells to r/r collagen. Of the stellate cell activation markers examined (tissue inhibitor of metalloproteinases-1, α-smooth muscle actin, matrix metalloproteinases-2 and -9, and procollagen I) only the last was decreased by culture on r/r collagen relative to normal collagen I. Antagonists of integrin αvβ3, an integrin reported to stimulate stellate cell proliferation, significantly inhibited adhesion, proliferation, and procollagen I synthesis of stellate cells plated on normal collagen I but had reduced effectiveness on these parameters in cells on r/r collagen. We conclude that pro- liferation of stellate cells is promoted by pericellular collagen I proteolysis acting via αvβ3 integrin. Cross-linking of collagen I by tissue transglutaminase, a process known to occur in chronic liver fibrosis, might not only increase its resistance to matrix metalloproteinases thereby inhibiting resolution of fibrosis but also functions to constrain the fibroproliferative process. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to analyze the independent risk factors that affect the treatment outcomes of residual symptoms of cured benign paroxysmal positional vertigoand to construct a nomogram model. METHODS: A total of 186 benign paroxysmal positional vertigo patients who were treated in our hospital from June 2019 to August 2021 were selected. According to whether there were residual symptoms, they were divided into a group with residual symptoms (n = 82) and a group without residual symptoms (n = 104). The logistic regression model was used to analyze the independent risk factors affecting the treatment outcomes, and the results were incorporated into R software to establish a nomogram model for verification. RESULTS: The incidence rate of residual symptoms in the 186 patients was 44.09% (82/186). Logistic regression analysis showed that age, course of disease, number of maneuvers, anxiety state, diabetes mellitus, and hypertension were independent risk factors affecting the treatment outcomes of residual symptoms after cured benign paroxysmal positional vertigo. The area under the receiver operating characteristic curve of the nomogram model was 0.938. The calibration curve was fitted well (χ² = 8.165, P = .417). CONCLUSION: The nomogram model constructed based on age, course of disease, number of maneuvers, anxiety state, diabetes mellitus, and hypertension had a high predictive value for the treatment outcomes of residual symptoms in benign paroxysmal positional vertigo patients. [ABSTRACT FROM AUTHOR]

We investigate theoretically the electronic properties of two-dimensional electron gases (2DEGs) with regular and distorted triangular antidot lattices. We show that the triangular antidot lattices embedded in 2DEGs behave like artificial graphene and host Dirac fermions. By introducing the Wannier representation, we obtain a tight-binding Hamiltonian including the second-nearest-neighboring hopping, which agrees well with the numerically exact solutions. Based on the tight-binding model, we find that spatially nonuniform distortions of the antidot lattices strongly modify the electronic structures, generate pseudomagnetic fields and the well-defined Landau levels. In contrast to graphene, we can design the nonuniform distortions to generate various configurations of pseudomagnetic fields. We show that the snake orbital states arise by designing the ±B pseudomagnetic field configuration. We find that the disorders of antidot lattices during fabrication would not affect the basic feature of the Dirac electrons, but they lead to a reduction in conductance in strong disorder cases. [ABSTRACT FROM AUTHOR]

We theoretically investigate the effective g factor in the black phosphorus (BP) thin films (TFs) based on a multiband k.p theory. We demonstrate that the effective single particle g factor in pristine BP TF is anisotropic arising from its anisotropic band structure with g*xx≈g*yy ≈ 2.0 and g*zz sensitively depending on the interband coupling and the band gap. The g*zz approaches 2.0 with increasing hole doping density and gate electric field since both of them minish the interband coupling by reducing the overlap integral between the electron and hole wave functions. We also estimate the exchange interaction enhancement on the effective single particle g factor by using the screened Hartree-Fock approximation. The exchange interaction enhanced g factor (gex) shows maxima (minima) at odd (even) filling factors. The effective g factor (g*) oscillates with the increase of magnetic field and sensitively depends on the Landau level broadening as well as the gate electric field since both of them affect the interband coupling and the electron-electron interactions. [ABSTRACT FROM AUTHOR]

We theoretically investigate the Landau levels (LLs) and magneto-optical conductivity (MOC) of black phosphorus thin films under a perpendicular magnetic field based on an effective k·p Hamiltonian and linear-response theory. We obtain the analytical expression for LLs, which agrees well with the numerical calculations, and find that the LLs sublinearly depend on the magnetic field and LL index. By using the Kubo formula, we evaluate the longitudinal and Hall optical conductivities as functions of the photon energy and the magnetic field. The analytical optical transition matrix elements reveal unusual selection rules for the interband (intraband) optical transitions between the LLs Δn=0,±2 (±1,±3). The MOC shows strongly anisotropic behaviors of the band structure. For the interband transition, the MOC for linearly polarized light along the armchair direction is three orders of magnitude larger than that along the zigzag direction. Interestingly, we find a beating pattern in the interband MOC due to the interference among the three kinds of optical transitions. For the intraband transition, the MOC can be used to determine the band parameters such as the effective masses and the interband coupling at zero magnetic field. Our results about the MOC can also be applied to the monolayer black phosphorus. [ABSTRACT FROM AUTHOR]

Ultrasound nanodroplets (NDs) have been reported as a promising nanocarrier for siRNA delivery depending on its unique strengths of sonoporation. Presently, common means for NDs-mediated siRNA delivery is through electrostatic interaction, but challenges like cationic toxicity still exist. In this study, we demonstrated a novel strategy to construct negatively charged and ultrasound (US)-responsive O-carboxymethyl chitosan (O-CMS) NDs as a siRNA targeted delivery system through three-way junction of bacteriophage phi29 DNA packaging motor (3WJ-pRNA) nanotechnology. 39nt A10-3.2 aptamer targeting prostate specific membrane antigen (PSMA) and 21nt siRNA against cationic amino acid transporter 1 (siCAT-1) were annealed to 3WJ-pRNA scaffold via complementation with an extended sequence. The cholesterol molecule attached to one branch facilitates the 3WJ-pRNA nanoparticles anchoring onto NDs. The desired O-CMS NDs with siRNA-loading and RNA-aptamer modification (A10-3.2/siCAT-1/3WJ-NDs) were successfully prepared, which were with spherical shapes, core-shell structures and uniform in sizes (198nm with PDI 0.3). As a main proportion of shell, O-CMC showed a certain anti-tumor effects. In vitro studies demonstrated that A10-3.2/siCAT-1/3WJ-NDs exhibited good contrast-enhanced US imaging, buffering capacity and high bio-safety, were able to deliver siCAT-1 to PSMA-overexpressed prostate cancer cells under US irradiation, thus silence the CAT-1 expression, and consequently suppressing 22RV1 cell proliferation and migration. Taken overall, our findings provide a promising strategy to develop negatively charged and US-responsive NDs for tumor-targeted siRNA delivery. [ABSTRACT FROM AUTHOR]

The construction of multifunctional oncotherapy nanoplatforms that combine diagnosis and treatment remains challenging. Nanodroplets (NDs), which simultaneously enhance ultrasound imaging and therapeutic effects, are a potential strategy for non-invasive drug delivery. To achieve the goals of precise medicine, novel SP94 peptide-modified and doxorubicin-loaded ultrasonic NDs (SP94-DOX-NDs) for castration-resistant prostate cancer (CRPC) targeting and treatment were constructed in this study. The characteristics, contrast-enhanced ultrasound imaging (CEUI), targeting ability to glucose-regulated protein 78 (GRP78)-overexpressing CRPC and anticancer effect of the SP94-DOX-NDs were assessed. The desired SP94-NDs were successfully prepared using the nanoemulsification method using a certain proportion of SP94-PEG-chitosan, perfluoropentane (PFP), Tween 20, and lecithin. SP94-NDs with a size of -300nm showed great biocompatibility and CEUI ability. Compared with blank NDs, SP94-NDs exhibited higher tumor-specific targeting ability due to conjugation between the SP94 peptide and GRP78-overexpressing 22RV1 cells. Most importantly, in vitro and in vivo investigations showed that SP94-DOX-NDs combined with ultrasound could specifically deliver DOX into 22RV1 cells and thereby demonstrated a stronger anticancer effect than DOX-NDs and DOX. Thus, SP94-DOX-NDs may provide an efficient approach for the real-time imaging of tumors and triggered, accurate drug delivery to tumors. [ABSTRACT FROM AUTHOR]

[Objective] This study was to investigate the efficiency and specificity of RNAi silencing on the expression of endogenous fad2 gene in transgenic line W-4. [Method] The relative expression of fad2 gene in seeds at different developmental stages of 7th, 14th, 21st and 28th day after flowering (DAF) as well as the root, stem, leaf at winter seedling stages of both the transgenic line W-4 and non-transgenic control Westar by real-time fluorescence quantitative PCR. [Results] The results showed the relative expression of fad2 gene was gradually increasing with the days after flowering in the seeds of the control Westar, while it was found decreasing significantly since the 21st DAF in the seeds of the line W-4. The decline was up to 60% in comparison with the control Westar. However, no significant difference in the relative expression of fad2 gene in other organs like root, stem and leaf was observed between transgenic line W-4 and non-transgenic control Westar. Fatty acid composition analysis showed the oleic acid desaturation parameter (ODP) in seeds of the line W-4 was 0.07 in average, decreased by nearly 75% than control Westar which was 0.24 in average, while no significant difference in the seedling root, stem and leaf was measured between transgenic rapeseed and control. [Conclusion] The results above validated that RNA interference in transgenic rapeseed W-4 is at a seed-specific manner, not interfering with fad2 gene expression in organs such as the root, stem and leaf. The study also found that the period of fad2 gene expression decline was well coincided with the expression of napin gene, both appeared at the 21st DAF, indicating that the expression of dsRNA of fad2 gene is precisely controlled by the napin promoter. [ABSTRACT FROM AUTHOR]

The genetically modified high-oleic rapeseed(Brassica napus L.) line W-4 was obtained by transforming a binary vector which harbored an inverted repeat expression cassette of fad2 gene into the rapeseed cultivar Westar. The transformation was mediated by Agrobacterium. The flanking sequences to both the left and right borders of T-DNA insertion site were amplified by thermal asymmetric interlaced PCR(TAIL-PCR) from the genomic DNA of the transgenic rapeseed line W-4. The flanking sequences to the right border was 290 bp in length and the nucleotide composition was 31.27% for G+C content while 68.73% for A+T content. The flanking sequence to the left border was 365 bp in length and the G +C content was 32.6% and the A+T content was 67.4%, indicating that the T-DNA was integrated in the A/T-rich region. Further more, sequence alignment analysis showed a deletion of 62 bp including the right border of pCNFIRnos and the integration of the whole left border except a change of G to A. That was to say, the integration of the T-DNA in the transgenic line W-4 not involved in the vector sequences. Based on both flanking sequences as well as the left and right borders of the T-DNA sequences,two pairs of specific primers TLF/TLR and TRF/TRR were designed. Using the primers the event-specific PCR detection method for transgenic rapeseed line W-4 was established. By the PCR, two fragments of 485 and 405 bp were amplified from the W-4 genomic DNA as expected, while no products were amplified from the genomic DNA of other transgenic rapeseed lines and non-transgenic rapeseed line.And by the PCR it is possible to detect the W-4 genomic DNA from a mixed sample of genomic DNA. The limit of the detection for the qualitative PCR assay was 0.1%. The method developed in this work is highly specific, sensitive and suitable for event-specific detection of the transgenic rapeseed line W-4. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB) caused by Fusarium graminearum is a destructive disease of wheat and barley worldwide. In a previous study of systematic characterization of protein kinase genes in F. graminearum, mutants of three putative components of the osmoregulation MAP kinase pathway were found to have distinct colony morphology and hyphal growth defects on PDA plates. Because the osmoregulation pathway is not known to regulate aerial hyphal growth and branching, in this study we further characterized the functions of the FgHog1 pathway in growth, pathogenesis, and development. The Fghog1, Fgpbs2, and Fgssk2 mutants were all reduced in growth rate, aerial hyphal growth, and hyphal branching angle. These mutants were not only hypersensitive to osmotic stress but also had increased sensitivity to oxidative, cytoplasm membrane, and cell wall stresses. The activation of FgHog1 was blocked in the Fgpbs2 and Fgssk2 mutants, indicating the sequential activation of FgSsk2-FgPbs2-FgHog1 cascade. Interestingly, the FgHog1 MAPK pathway mutants appeared to be sensitive to certain compounds present in PDA. They were female sterile but retained male fertility. We also used the metabolomics profiling approach to identify compatible solutes that were accumulated in the wild type but not in the Fghog1 deletion mutant. Overall, our results indicate that the FgSsk2-FgPbs2-FgHog1 MAPK cascade is important for regulating hyphal growth, branching, plant infection, and hyperosmotic and general stress responses in F. graminearum. [ABSTRACT FROM AUTHOR]

Objective: This paper investigates the total polyphenolic and flavonoid content as well as the antioxidant activity of Ziziphora clinopodioides Lam. extracts of different polarity. Materials and Methods: The total polyphenolic content was analysed using the Folin- Ciocalteu method. Total flavonoid content analysis was performed using the colorimetric method. Results: The total polyphenolic content of Z. clinopodioides is concentrated in parts of ethyl acetate (19.27%), chloroform (4.99%) and n-butanol extracts (3.94%) containing a small amount of the total polyphenolic content. The petroleum ether (0.23%) and ethanol extracts (1.64%) contain almost no polyphenolic content. The total flavonoid content of Z. clinopodioides is concentrated in parts of ethyl acetate (65.61%), chloroform (14.36%) and n-butanol extracts (10.76%) containing a small amount of the total polyphenolic content. The Z. clinopodioides Lam. ethyl acetate extract exhibits a good antioxidant activity. Conclusion: Ethyl acetate extracts contain a large number of polyphenolic compounds (19.27%) and flavonoids (65.61%) owing to good antioxidant capacity. [ABSTRACT FROM AUTHOR]

Background: Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, TFPI-2 was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether TFPI-2 was inactivated epigenetically in nasopharyngeal carcinoma (NPC). Methods: Transcriptional expression levels of TFPI-2 was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of TFPI-2 as a tumor suppressor gene in NPC was addressed by re-introducing TFPI-2 expression into the NPC cell line CNE2. Results: TFPI-2 mRNA transcription was inactivated in NPC cell lines. TFPI-2 was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. TFPI-2 expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration. Conclusions: Epigenetic inactivation of TFPI-2 by promoter hypermethylation is a frequent and tumor specific event in NPC. TFPI-2 might be considering as a putative tumor suppressor gene in NPC. [ABSTRACT FROM AUTHOR]

Trichothecenes are isoprenoid mycotoxins produced in wheat infected with the filamentous fungus Fusarium graminearum. Some fungal genes for trichothecene biosynthesis ( Tri genes) are known to be under control of transcription factors encoded by Tri6 and Tri10. Tri6 and Tri10 deletion mutants were constructed in order to discover additional genes regulated by these factors in planta. Both mutants were greatly reduced in pathogenicity and toxin production and these phenotypes were largely restored by genetic complementation with the wild-type gene. Transcript levels for over 200 genes were altered ≥ twofold for Δtri6 or Δtri10 mutants including nearly all known Tri genes. Also reduced were transcript levels for enzymes in the isoprenoid biosynthetic pathway leading to farnesyl pyrophosphate, the immediate molecular precursor of trichothecenes. DNA sequences 5′ to isoprenoid biosynthetic genes were enriched for the Tri6p DNA binding motif, YNAGGCC, in F. graminearum but not in related species that do not produce trichothecenes. To determine the effect of trichothecene metabolites on gene expression, cultures were treated with trichodiene, the first metabolic intermediate specific to the trichothecene biosynthetic pathway. A total of 153 genes were upregulated by added trichodiene and were significantly enriched for genes likely involved in cellular transport. Differentially regulated genes will be targeted for functional analysis to discover additional factors involved in toxin biosynthesis, toxin resistance and pathogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUNDThere has been a striking generational increase in the prevalence of food allergies. We have proposed that this increase can be explained, in part, by alterations in the commensal microbiome.METHODSTo identify bacterial signatures and metabolic pathways that may influence the expression of this disease, we collected fecal samples from a unique, well-controlled cohort of twins concordant or discordant for food allergy. Samples were analyzed by integrating 16S rRNA gene amplicon sequencing and liquid chromatography-tandem mass spectrometry metabolite profiling.RESULTSA bacterial signature of 64 operational taxonomic units (OTUs) distinguished healthy from allergic twins; the OTUs enriched in the healthy twins were largely taxa from the Clostridia class. We detected significant enrichment in distinct metabolite pathways in each group. The enrichment of diacylglycerol in healthy twins is of particular interest for its potential as a readily measurable fecal biomarker of health. In addition, an integrated microbial-metabolomic analysis identified a significant association between healthy twins and Phascolarctobacterium faecium and Ruminococcus bromii, suggesting new possibilities for the development of live microbiome-modulating biotherapeutics.CONCLUSIONTwin pairs exhibited significant differences in their fecal microbiomes and metabolomes through adulthood, suggesting that the gut microbiota may play a protective role in patients with food allergies beyond the infant stage.TRIAL REGISTRATIONParticipants in this study were recruited as part of an observational study (ClinicalTrials.gov NCT01613885) at multiple sites from 2014 to 2018.FUNDINGThis work was supported by the Sunshine Charitable Foundation; the Moss Family Foundation; the National Institute of Allergy and Infectious Diseases (NIAID) (R56AI134923 and R01AI 140134); the Sean N. Parker Center for Allergy and Asthma Research; the National Heart, Lung, and Blood Institute (R01 HL 118612); the Orsak family; the Kepner family; and the Stanford Institute for Immunity, Transplant and Infection. [ABSTRACT FROM AUTHOR]

A fiber sphere-embedded long-period fiber grating (LPFG) sensor has been proposed and fabricated for curvature measurement with high sensitivity. Compared with the normal LPFG, the embedded fiber sphere excites cladding modes and two dips of the output spectrum have been observed. The curvature measurement can be realized by monitoring the shift of the two dips. Experimental results show that the highest curvature sensitivity is up to -104.642 nm/m-1 with the curvature ranging from 0 to 0.71 m-1. The temperature response of the sensor has also been studied and a quadratic linear relationship between the dip shift and the temperature has been observed. The highest temperature sensitivity is 0.36 nm/°C with the temperature range between 20°C and 90°C. [ABSTRACT FROM AUTHOR]

Background: Subjects with elevated Epstein-Barr virus (EBV) immunoglobulin A (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC), indicating that reactivation of EBV in the local mucosa might be important for NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk factors for NPC. However, it remains unclear whether smoking-induced nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal mucosa. Therefore, this study aims to investigate the association between cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk population.Methods: A NPC high-risk cohort study, established from a population-based NPC screening program of 22,816 subjects, consisted of 1045 subjects with elevated serum IgA antibodies against EBV viral capsid antigen (VCA/IgA). Among high-risk subjects, information on detailed cigarette smoking history was collected among 313 male subjects. The associations between cigarette smoking and EBV antibody levels, EBV DNA load of the nasopharynx were analyzed.Results: No significant association was observed between either nasopharyngeal EBV DNA load or serum VCA/IgA titers and smoking status, age at smoking initiation, daily smoking intensity, smoking duration, cigarette type, or pack-years of smoking. Cigarette smoking characteristics in all subgroups did not correlate with nasopharyngeal EBV DNA positivity or EBV VCA/IgA seropositivity.Conclusions: In a population at high risk of NPC, our study suggests that cigarette smoking is neither associated with nasopharyngeal EBV DNA load nor serum VCA/IgA antibody level. Smoking-associated NPC carcinogenesis may act through other mechanisms than reactivating nasopharyngeal EBV replication. [ABSTRACT FROM AUTHOR]

We study the variation of electronic property for zigzag-edge phosphorene nanoribbons (ZPNRs) under a perpendicular electric field (PEF). Using the tight-binding Hamiltonian combined with the surface lattice Green’s function (GF) approach, we show that the response of edge states to PEF for a N-ZPNR with even- or odd-N (number of zigzag chains) is qualitatively different. The field opens a gap between two edge bands near the Fermi energy for even-N ribbons, but for odd-N ones where the two edge bands are always nearly degenerated. This difference is originally from that the Stark-effect-induced energies at the upper and lower edges for even- and odd-N ZPNRs are different due to the peculiar lattice structure of phosphorene. In consequence, the electronic densities are more localized at the edges driven by the field for even-N ZPNRs but not for odd-N ones. This even–odd effect is also reflected in conductance, which indicates that the odd-N ZPNRs may be more suitable for the usage of field-effect transistor. [ABSTRACT FROM AUTHOR]

Metastasis of lung carcinoma cells is a major cause of organ failure and mortality of patients with lung cancer. Lung mast cells are a type of immune cell which reside in the respiratory mucosa. High numbers of mast cells are associated with the majority of common types of cancer; however, the effects of mast cells on cancer remain unclear. In the present study, the effects of mast cell chymase (MCC) on the proliferation and adhesion of the lung carcinoma cell lines A549 and H520 was investigated. After 24 h of treatment, the highest dose of MCC (50 mU/ml) decreased the proliferation rate of A549 and H520 cells, whereas the lowest dose of MCC (5 mU/ml) resulted in a small increase in the viability. A549 cells treated with MCC lost adhesion ability in a MCC dose-dependent manner; however, these detached cells were able to regrow when transferred to a fresh culture. The protein expression of epithelial (E-) cadherin, p53 and p21 in A549 lung carcinoma cells were detected by western blot analysis. The results of the present study revealed that, following 24 h of treatment, the expression level of E-cadherin was decreased, the p53 tumor suppressor protein was expressed in limited quantities and the expression of p21 was decreased. Zymography was used to examine the effects of MCC on the expression and activation of matrix metalloproteinase-9 (MMP-9) in A549 and H520 cells. The expression of MMP-9 in the two cell lines was time- and MCC dose-dependent. The results of the present study demonstrated that MCC stimulated lung carcinoma cell proliferation and adhesion, as well as regulated E-cadherin expression and the cell cycle, all of which are associated with cancer metastasis. Therefore, MCC may be a potential candidate for lung carcinoma therapy. [ABSTRACT FROM AUTHOR]

We demonstrate that the subradiant mode in ultrathin bi-layer metamaterials can be exclusively excited under two-antisymmetric-beam illumination (or equivalently, at a node of the standing wave field), while the superradiant mode is fully suppressed due to their different mode symmetry. Coherent perfect absorption (CPA) with the Lorentzian lineshape can be achieved corresponding to the subradiant mode. A theoretical model is established to distinguish the different behaviors of these two modes and to elucidate the CPA condition. Terahertz ultrathin bi-layer metamaterials on flexible polyimide substrates are fabricated and tested, exhibiting excellent agreement with theoretical predictions. This work provides physical insight into how to selectively excite the antisymmetric subradiant mode via coherence incidence. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease and derived from immune granule cells. It has been suggested playing an important role in the development of rheumatoid arthritis. In this study, a coumarin based fluorescent probe (GF-AFC) was designed and synthesized to evaluate DPPI activity in serum or tissue homogenates of collagen-induced arthritis (CIA) rats, an inflammatory arthropathy model. It was revealed that the fluorescent intensity was significantly increased in a very short time after specific substrate GF-AFC reacted with the DPPI. The fluorophore (AFC) was released to shine after the cleavage reaction which was examined by 19F NMR spectroscopy. It has been shown that DPPI hydrolyzed the GF-AFC in a robust, linear, and time dependent manner at a significant high rate. A serum-based DPPI activity assay was validated by spiking and gradient dilution methods, there were no interferences or auto-fluorescence observed. The Coefficient of Variance calculated for serum-based DPPI activity assays indicates the good reproducibility. The good correlation has been seen between serum DPPI levels and the severity of arthritis during RA development in CIA rats. Our study has demonstrated a new serum based diagnostic assay for detecting DPPI activity using coumarin conjugated fluorescent (GF-AFC) as a substrate. The successful implementation of the case would provide beneficial experience in rheumatoid arthritis research. [ABSTRACT FROM AUTHOR]

Apolipoprotein D (ApoD) is an essential protein for insect internal circulation because of its role in lipid transportation. In this study, we cloned and characterized ApoD and analyzed its expression characteristics in Bombyx mori (L.) (Lepidoptera: Bombycidae). The ApoDcDNA fragment, which has an open reading frame of 522 bp with a lipo-calin domain (PF08212), encodes 174 amino acids. The deduced ApoD protein sequence has 28.2% identity to its ortholog in Mus musculus and 27.8% identity to its ortholog GLaz in Drosophila melanogaster. Several putative cis-acting elements related to development were also examined. Using quantitative real time polymerase chain reaction (RT-PCR), the ApoD gene expression was detected in the head and silk glands. Western blotting showed that ApoD protein was present in the head, hemolymph, fat body, gonad, middle silk gland, and posterior silk gland. ApoD expression was relatively higher in the hemolymph during days 1-3 of fifth-instar larvae and days 6-8 of the pupal stage. The highest mRNA levels were detected in the pupae on day 9 by using quantitative RT-PCR. After an oxidative stress treatment and a bacterial challenge, expression levels of the ApoD gene from B. mori were up-regulated at different time points compared with the control group. Simultaneously, immunohistochemi-cal localization showed that ApoD is widely detected in the brain, eye, ovary, and testis on day 3 of the fifth-instar larval stage. The results indicated that ApoD is involved in insect development and reproduction, and plays an important role in the response to bacterial challenge and other stress signals. [ABSTRACT FROM AUTHOR]

Introduction: Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Methods: Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. Results: 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. Conclusions: This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. [ABSTRACT FROM AUTHOR]

[Objective] To cultivate blanket rapeseed seedlings suitable for automatic mechanical transplanting, the effects of seed soaking with uniconazole and substrate formula on seed germination and seedling quality of rapeseed were investigated using HY4 as the material. [Method] The rapeseed seeds were soaked in different concentrations (0, 5, 10, 20, 30, 40 and 50 mg/L) of uniconazole for 0, 1, 2, 4 and 8 h, respectively. Subsequently, they were dried naturally. After the preliminary screening carried out in petri dishes and in a laboratory, the optimum soaking concentration and time of uniconazole were obtained. On the other hand, the rapeseed seeds were soaked in different concentrations (0, 5, 10, 15 and 20 mg/L) of uniconazole for 0, 1 and 2 h, respectively for outdoor pot experiment. At the same time, the screening of optimum substrate formula for cultivating blanket rapeseed seedlings was carried out. The field test was carried out to verify the screened optimum substrate formula. [Result] The results of petri dish experiment showed that seed soaking with uniconazole could delay seed germination, reduce seed germination rate, inhibit hypocotyl elongation and promote root growth. When the soaking concentration exceeded 30 mg/L and soaking time exceeded 2 h, the effect of seed soaking with uniconazole on seed germination was greater, and the seed soaking inhibited root growth. The results of outdoor pot experiment showed that the soaking concentrations and times all significantly reduced seedling height, slowed shoot growth and promoted root growth, which all contributed to the cultivation of blanket rapeseed seedlings suitable for automatic mechanical transplanting. In the substrate formula, the lower the proportion of soil was, the better the seedling growth was. In the substrate with lower proportion of soil, the seed germination rate, plant height, root vigor and dry matter accumulation were all increased (P<0.05), which was verified by the field test. When the soaking concentration was less than 10 mg/L and soaking time was less than 1 h, the uniconazole showed weaker regulation effect on seedling growth, and the rapeseed seedlings were higher. In the substrate with soil proportion less than 50%, the adequate fertility relatively weakened the regulation effect of uniconazole on seedling growth, and the rapeseed seedlings were larger. [Conclusion] When the soaking concentration ranged within 15-20 mg/L and soaking time ranged within 1-2 h and the proportion of soil in substrate was 50%, the height of cultivated rapeseed seedlings was less than 18 cm, there were 5-6 leaves remained on each plant and the nursing period was shortened to 30-40 d, which were all beneficial to industrial production. [ABSTRACT FROM AUTHOR]

Background: Silencing of tumor suppressor genes (TSGs) or activation of oncogenes by, e.g., aberrant promoter methylation, may be early events during carcinogenesis. The methylation status of such genes can be used for early detection of cancer. We are pursuing this approach in our efforts to develop markers for early detection and follow-up of nasopharyngeal carcinoma (NPC). We set out to develop this approach to allow identification of NPC from Morocco and then also compared with NPC samples from different geographical locations and different ethnicity with different NPC incidences, Epstein-Barr virus (EBV) prevalence, and environments. Results: By multiplex methylation-specific PCR (MMSP), multiple relevant genes can be detected simultaneously, to achieve high sensitivity and specificity. The strong association of EBV with NPC is also very useful in such an approach. We have initially screened for 12 potential marker genes including EBV genes coding for EBV nuclear antigen 1 (EBNA1) and latent membrane protein-1 (LMP1) and ten potential TSGs obtained from previously published data. The resulting assay included EBNA1, LMP1, and three cellular TSGs: ITGA9, RASSF1A, and P16. We evaluated this assay on 64 NPC patient biopsies from Morocco, Italy, and China compared to deoxyribonucleic acid (DNA) from 20 nasopharyngeal control tissues. In the Moroccan NPC cohort (n = 44), prevalence of the EBNA1 gene showed the highest sensitivity (36/44; 82 %) with 94 % specificity. Out of eight (18 %) EBNA1 negative Moroccan samples, only three were positive for at least one methylated cellular gene. By detection of cellular marker genes, the sensitivity increased from 82 to 89 % (39/44). In the whole material of 64 biopsies from three geographical locations, at least any one marker (viral or cellular) could be detected in 91 % of biopsies with 90 % specificity. In a pilot evaluating assay performance on serum DNA from NPC and controls including samples from Italy (n = 11) and China (n = 5), at least any one marker from the MMSP assay could be detected in 88 %, but the specificity was only 50 %. Conclusions: An MMSP assay has the potential for detection of NPC by screening in high-risk populations. Serum-derived DNA seems not as good as earlier published NPC swab DNA for screening purpose. [ABSTRACT FROM AUTHOR]

To clarify the effect of down-regulated expression of fad2 gene on the seed nutritional quality of rapeseed, the fatty acid composition, amino acid composition, oil content, protein content, crude fiber content and glucosinolate content in the seeds of both transgenic line W-4 and its control Westar were compared. The results showed that the oleic acid content in W-4 was 86.03% ±0.20%, which was 29.36% higher than that in the control (P<0.01); the linoleic acid content was 2.86%土 0.01%, which was reduced by 84.03% compared with that in the control (P<0.01); the linolenic acid content in W-4 was 3.040/。±0.040/。，reduced by 57.60%。(P<0.01); the palmitic acid content in W-4 was 3.23%±0.07%, reduced by 18.63% (P<0.01); the eicosenoic acid content in W-4 was increased by 18.46% compared with that in the control (P<0.01); the erucic acid content in W-4 was increased by 13.15% (P< 0.05); there was no significant difference in stearic acid content between the treatment and control groups (P>0.05). The amino acid composition analysis showed that total 18 amino acids, including 8 essential amino acids, were detected in both W-4 and Westar; there were no significant differences in contents of the 18 amino acids between the treatment and control groups except that of tyrosine (P>0.05); the contents of oil, proteins, glucosinolates and crude fiber in W-4 were 45.40% ± 0.17% (P>0.05),（P>0.05), 18.20%±1.21%（$>0.05) and 12.29% ± 0.04% (P>0.05), respectively. All the results above showed that the down-regulated expression of fad2 had great effects on fatty acid composition and accumulation in rapeseed seeds, but had no significant effects on other seed quality traits, such as oil content, protein content, crude fiber content and glucosinolate content. [ABSTRACT FROM AUTHOR]

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these tran-scriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from -10% to as much 40% of the tran-scriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-pro-moter activation as reported by ccg-promoter-luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. [ABSTRACT FROM AUTHOR]

Arginine methylation of non-histone proteins by protein arginine methyltransferase (PRMT) has been shown to be important for various biological processes from yeast to human. Although PRMT genes are well conserved in fungi, none of them have been functionally characterized in plant pathogenic ascomycetes. In this study, we identified and characterized all of the four predicted PRMT genes in Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. Whereas deletion of the other three PRMT genes had no obvious phenotypes, the Damt1 mutant had pleiotropic defects. AMT1 is a predicted type I PRMT gene that is orthologous to HMT1 in Saccharomyces cerevisiae. The Δamt1 mutant was slightly reduced in vegetative growth but normal in asexual and sexual reproduction. It had increased sensitivities to oxidative and membrane stresses. DON mycotoxin production and virulence on flowering wheat heads also were reduced in the Δamt1 mutant. The introduction of the wild-type AMT1 allele fully complemented the defects of the Δamt1 mutant and Amt1-GFP fusion proteins mainly localized to the nucleus. Hrp1 and Nab2 are two hnRNPs in yeast that are methylated by Hmt1 for nuclear export. In F. graminearum, AMT1 is required for the nuclear export of FgHrp1 but not FgNab2, indicating that yeast and F. graminearum differ in the methylation and nucleo-cytoplasmic transport of hnRNP components. Because AMT2 also is a predicted type I PRMT with limited homology to yeast HMT1, we generated the Δamt1 Δamt2 double mutants. The Δamt1 single and Δamt1 Δamt2 double mutants had similar defects in all the phenotypes assayed, including reduced vegetative growth and virulence. Overall, data from this systematic analysis of PRMT genes suggest that AMT1, like its ortholog in yeast, is the predominant PRMT gene in F. graminearum and plays a role in hyphal growth, stress responses, and plant infection. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatic stellate cells (HSC) are known to synthesise excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the matrix-degrading matrix metalloproteinase enzymes (MMPs) and their tissue inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis, the expression of TIMP-1 declines and hepatic collagenolytic activity increases. This is accompanied by HSC apoptosis. In this study, we examine a potential mechanism whereby MMP activity might induce HSC apoptosis by cleaving N-cadherin at the cell surface. Results: N-cadherin expression was upregulated in human HSC during activation in culture. Addition of function-blocking antibodies or a peptide targeting the extracellular domain of N-cadherin, to cultured HSC, promoted apoptosis. During apoptosis, there was cleavage of N-cadherin into 20–100 kDa fragments. MMP-2 became activated early during HSC apoptosis and directly cleaved N-cadherin in vitro. Addition of activated MMP-2 to HSCs in culture resulted in enhanced apoptosis and loss of N-cadherin. Conclusions: Together, these studies identify a role for both N-cadherin and MMP-2 in mediating HSC apoptosis, where N-cadherin works to provide a cell survival stimulus and MMP-2 promotes HSC apoptosis concomitant with N-cadherin degradation. [ABSTRACT FROM AUTHOR]

We study the influence of electrodes on the exponential transport rule for the junction of oligophenylene-linked and oligoacene-linked molecules between two zigzag phosphorene nanoribbons (ZPNRs), where molecules consisting of one, two and three benzene rings are considered, respectively. We find by ab initio calculations that the amplitude of current through the junction is dependent on both the molecular length and the molecule–ZPNR coupling manner. In specification, the current through the single-bond coupled junction with the molecular plane perpendicular to the ZPNRs is almost two times that with parallel configuration due to the greater number of transport channels provided by the p y  orbital in the former case. In contrast, the current of the junction with double-bond coupling is nearly two orders of magnitude larger because of the stronger coupling strength. Nevertheless, in any case the ZPNR–electrode junction, like metal–electrode junctions, also obeys the exponential decaying rule in transport with the variation of molecular length. Importantly, the relationship between the resistance and the molecular length, regardless of the coupling details, can be fitted by a linear line in the semilog coordinate but with different slopes determined by the coupling manner. This indicates that the exponential rule of transport under small bias voltages is electrode-material-independent for molecular junctions with any electrode. But the value of the decaying factor, importantly, is heavily dependent not only on the molecule itself but also on the electrode materials as well as the molecule–electrode coupling method. [ABSTRACT FROM AUTHOR]