Much of the experimental evidence available is from animal models, cell lines or non-strictured patient tissue. Accordingly, these limitations create the basis for many previously published reviews covering the topic. Although this information has contributed to the understanding of fibrotic mechanisms in general, in the end, data must be validated in strictured tissue from patients. As stricture formation is a serious complication of CD, we endeavoured to summarize findings exclusively performed using strictured tissue from patients. Here, we give an update of the mechanism driving this serious complication in patients, and how the strictured tissue differs from adjacent unaffected tissue and controls.Floral nectar is a sugary solution produced by nectaries to attract and reward pollinators. Nectar metabolites, such as sugars, are synthesized within the nectary during secretion from both pre-stored and direct phloem-derived precursors. In addition to sugars, nectars contain nitrogenous compounds such as amino acids; however, little is known about the role(s) of nitrogen (N) compounds in nectary function. In this study, we investigated N metabolism in Cucurbita pepo (squash) floral nectaries in order to understand how various N-containing compounds are produced and determine the role of N metabolism in nectar secretion. The expression and activity of key enzymes involved in primary N assimilation, including nitrate reductase (NR) and alanine aminotransferase (AlaAT), were induced during secretion in C. pepo nectaries. Alanine (Ala) accumulated to about 35% of total amino acids in nectaries and nectar during peak secretion; however, alteration of vascular nitrate supply had no impact on Ala accumulation during secretion, suggesting that nectar(y) amino acids are produced by precursors other than nitrate. In addition, nitric oxide (NO) is produced from nitrate and nitrite, at least partially by NR, in nectaries and nectar. Hypoxia-related processes are induced in nectaries during secretion, including lactic acid and ethanolic fermentation. Finally, treatments that alter nitrate supply affect levels of hypoxic metabolites, nectar volume and nectar sugar composition. The induction of N metabolism in C. pepo nectaries thus plays an important role in the synthesis and secretion of nectar sugar.

This study aimed to investigate the antibacterial ability and action mechanism of dithiocyano-methane against Aeromonas hydrophila, so as to provide a reference for its application in farm disinfection.

After exposing the bacteria to dithiocyano-methane, the minimum inhibitory concentration (MIC), minimum bactericide concentration (MBC), activities of alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and electric conductivity in bacterial suspensions were determined, transmission electron microscope images on cellular structure and SDS-PAGE profile of bacterial proteins were analysed and the expression of genes related to the above experimental observations was confirmed by real-time quantitative PCR. The MIC and MBC of dithiocyano-methane against three tested strains was 1·46 and 2·93mgl

respectively. The results showed that dithiocyano-methane significantly damaged bacterial cell structure, inhibited the biosynthesis of bacterial proteins and changed the integrity and permeability of bacterial cell wall and cell membrane.

Dithiocyano-methane showed remarkable antibacterial ability against three tested strains, indicating it is a potential effective bactericidal agent for preventing animal diseases resulted from Aer. hydrophila.

To our best knowledge, this is the first report to examine the antibacterial ability and action mechanism of dithiocyano-methane against bacteria. The results demonstrate the great potential of dithiocyano-methane as a disinfectant against Aer. hydrophila in settings such as aquaculture ponds and livestock farms.

To our best knowledge, this is the first report to examine the antibacterial ability and action mechanism of dithiocyano-methane against bacteria. The results demonstrate the great potential of dithiocyano-methane as a disinfectant against Aer. hydrophila in settings such as aquaculture ponds and livestock farms.The crude methanolic extract obtained from Verbascum nigrum aerial parts (VNE) and its six fractions (VNF1-VNF6) were initially screened regarding their effects on the viability of immortalized HaCaT keratinocytes and A431 epidermoid carcinoma cells (MTT assay, 24 h). None of the tested samples affected the viability of HaCaT cells in a concentration range of 25-150 μg/mL. VNE and VNF4 exhibited significant cytotoxic effects in A431 cells, with IC50 values of 81.92 and 12.27 μg/mL, respectively; the selectivity index was higher than 10 for VNF4. The untargeted LC/HR-MS/MS metabolite profiling led to the tentative annotation of a total number of 23 compounds. Of these, VNE comprised mainly iridoid glycosides (harpagoside, laterioside, acylated aucubin derivatives), whereas VNF4 showed a high abundance of triterpene saponin glycosides (ilwensisaponins A and C, songarosaponins A and B), constituents known for their selective cytotoxic potential.Senescence is an integrative final stage of plant development that is governed by internal and external cues. The NAM, ATAF1/2, CUC2 (NAC) transcription factor (TF) family is specific to plants and membrane-tethered NAC TFs (MTTFs) constitute a unique and sophisticated mechanism in stress responses and development. However, the function of MTTFs in oilseed rape (Brassica napus L.) remains unknown. Here, we report that BnaNAC60 is an MTTF associated with the endoplasmic reticulum (ER) membrane. Expression of BnaNAC60 was induced during the progression of leaf senescence. Translocation of BnaNAC60 into nuclei was induced by ER stress and oxidative stress treatments. It binds to the NTLBS motif, rather than the canonical NAC recognition site. Overexpression of BnaNAC60 devoid of the transmembrane domain, but not the full-length BnaNAC60, induces significant reactive oxygen species (ROS) accumulation and hypersensitive response-like cell death in both tobacco (Nicotiana benthamiana) and oilseed rape protoplasts. Moreover, ectopic overexpression of BnaNAC60 devoid of the transmembrane domain, but not the full-length BnaNAC60, in Arabidopsis also induces precocious leaf senescence. Furthermore, screening and expression profiling identified an array of functional genes that are significantly induced by BnaNAC60 expression. Further it was found that BnaNAC60 can activate the promoter activities of BnaNYC1, BnaRbohD, BnaBFN1, BnaZAT12, and multiple BnaVPEs in a dual-luciferase reporter assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation coupled to quantitative PCR assays revealed that BnaNAC60 directly binds to the promoter regions of these downstream target genes. To summarize, our data show that BnaNAC60 is an MTTF that modulates cell death, ROS accumulation, and leaf senescence.The inverse relationship between transcription factor MITF and receptor tyrosine kinase AXL has received much attention recently. It is thought that melanoma tumors showing AXLhigh /MITFlow levels are resistant to therapy. We show here that a population of cells within melanoma tumors with extremely high expression of AXL are negative/low for both MITF and the transcription factor BRN2. Depletion of both transcription factors from cultured melanoma cell lines produced an increase in AXL expression greater than depletion of MITF alone. Further, re-expression of BRN2 led to decreased AXL expression, indicating a role for BRN2 in regulation of AXL levels unrelated to effects on MITF level. As AXL has been recognized as a marker of therapy resistance, these cells may represent a population of cells responsible for disease relapse and as potential targets for therapeutic treatment.

What is the topic of this review? This review highlights the central and peripheral mechanisms that alter oxygen transport and utilisation and thereby contribute to exercise limitation in people with cystic fibrosis, considering also viable therapeutic targets for intervention. What advances does it highlight? Although traditionally considered a respiratory condition, pathological intramuscular and cardiovascular changes in people with cystic fibrosis appear to be key determinants of exercise intolerance up until the later stages of respiratory disease. Even young, habitually active patients with normal lung function experience multisystemic abnormalities, which play a role in exercise intolerance.

Cystic fibrosis (CF) is a complex condition, commonly associated with exercise limitation. The mechanisms responsible for this in CF are of interest, given that lower aerobic fitness is associated with an increased risk of being hospitalised with pulmonary exacerbation, a poorer quality of life and a poorer propeutic interventional strategies.

Decision support tools improve decisional conflict and elicit patient preferences related to prostate cancer treatment. It was hypothesized that men using the Personal Patient Profile-Prostate (P3P) would be more likely to pursue guideline-concordant treatment.

Men from a trial assessing the P3P decision support intervention were identified. The primary exposure was allocation to P3P (vs usual care), and the outcome was appropriate treatment per guidelines (eg, low risk = active surveillance). It was assessed whether providers recommended against any treatment options (ie, restricted). A multivariable model was fit for men with low-risk cancer that estimated the odds of the outcome of interest.

This study identified 295 men in the cohort 113 (38%) had low-risk disease, 119 (40%) had favorable intermediate-risk disease, and 63 (21%) had unfavorable intermediate-risk disease. Among low-risk patients, more men pursued active surveillance after using P3P whether they were given unrestricted (62% vs 54% withth more appropriate alignment of treatment with disease risk.Species interactions such as mimicry can promote trait convergence but disentangling this effect from those of shared ecology, evolutionary history, and niche conservatism is often challenging. Here by focusing on wing colour pattern variation within and between three butterfly species living in sympatry in a large proportion of their range, we tested the effect of species interactions on trait diversification. These butterflies display a conspicuous iridescent blue coloration on the dorsal side of their wings and a cryptic brownish colour on the ventral side. Combined with an erratic and fast flight, these colour patterns increase the difficulty of capture by predators and contribute to the high escape abilities of these butterflies. We hypothesize that, beyond their direct contribution to predator escape, these wing patterns can be used as signals of escape abilities by predators, resulting in positive frequency-dependent selection favouring convergence in wing pattern in sympatry. To test this hypothesis, we quantified dorsal wing pattern variations of 723 butterflies from the three species sampled throughout their distribution, including sympatric and allopatric situations and compared the phenotypic distances between species, sex and localities. We detected a significant effect of localities on colour pattern, and higher inter-specific resemblance in sympatry as compared to allopatry, consistent with the hypothesis of local convergence of wing patterns. Our results provide support to the existence of escape mimicry in the wild and stress the importance of estimating trait variation within species to understand trait variation between species, and to a larger extent, trait diversification at the macro-evolutionary scale.