Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

We compare genome sequences of three closely related soft-rot pathogens that vary in host range and geographical distribution to identify genetic differences that could account for lifestyle differences. The isolates compared, Pectobacterium atrosepticum SCRI1043, P. carotovorum WPP14, and P. brasiliensis 1692, represent diverse lineages of the genus. P. carotovorum and P. brasiliensis genome contigs, generated by 454 pyrosequencing ordered by reference to the previously published complete circular chromosome of P. atrosepticum genome and each other, account for 96% of the predicted genome size. Orthologous proteins encoded by P. carotovorum and P. brasiliensis are approximately 95% identical to each other and 92% identical to P. atrosepticum. Multiple alignment using Mauve identified a core genome of 3.9 Mb conserved among these Pectobacterium spp. Each core genome is interrupted at many points by species-specific insertions or deletions (indels) that account for approximately 0.9 to 1.1 Mb. We demonstrate that the presence of a hrpK-like type III secretion system-dependent effector protein in P. carotovorum and P. brasiliensis and its absence from P. atrosepticum is insufficient to explain variability in their response to infection in a plant. Additional genes that vary among these species include those encoding peptide toxin production, enzyme production, secretion proteins, and antibiotic production, as well as differences in more general aspects of gene regulation and metabolism that may be relevant to pathogenicity.

Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100nM to 200nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100nM to 500nM. Intraperitoneal injection with a dosage of 5mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound.

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Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.

These results revealed obvious regional variation in cyantraniliprole susceptibilities among populations of S. litura from different areas, and potential cross-resistance to chlorantraniliprole, which suggested that S. litura could develop resistance to cyantraniliprole. Detoxification enzymes might not be involved in the observed tolerance in field-collected populations and the cyantraniliprole-resistant strain.

Fusarium head blight (FHB) is a destructive wheat disease present throughout the world, and host resistance is an effective and economical strategy used to control FHB. Lack of adequate resistance resource is still a main bottleneck for FHB genetics and wheat breeding research. The synthetic-derived bread wheat line C615, which does not carry the Fhb1 gene, is a promising source of FHB resistance for breeding. A population of 198 recombinant inbred lines (RILs) produced by crossing C615 with the susceptible cultivar Yangmai 13 was evaluated for FHB response using point and spray inoculations. As the disease phenotype is frequently complicated by other agronomic traits, we used both traditional and multivariate conditional QTL mapping approaches to investigate the genetic relationships (at the individual QTL level) between FHB resistance and plant height (PH), spike compactness (SC), and days to flowering (FD). A linkage map was constructed from 3,901 polymorphic SNP markers, which covered 2,549.2 cM. Traditional and conditional QTL mapping analyses found 13 and 22 QTL for FHB, respectively; 10 were identified by both methods. Among these 10, three QTL from C615 were detected in multiple years; these QTL were located on chromosomes 2AL, 2DS, and 2DL. Conditional QTL mapping analysis indicated that, at the QTL level, SC strongly influenced FHB in point inoculation; whereas PH and SC contributed more to FHB than did FD in spray inoculation. The three stable QTL (QFhbs-jaas.2AL, QFhbp-jaas.2DS, and QFhbp-jaas.2DL) for FHB were partly affected by or were independent of the three agronomic traits. The QTL detected in this study improve our understanding of the genetic relationships between FHB response and related traits at the QTL level and provide useful information for marker-assisted selection for the improvement of FHB resistance in breeding.

We previously developed a series of anticancer agents based on cyclooxygenase-2 (COX-2) inhibitor nimesulide as a lead compound. However, the molecular targets of these agents still remain unclear. In this study, we synthesized a biotinylated probe based on a representative molecule of the compound library and performed protein pull-down assays to purify the anticancer targets of the compound. Via proteomic approaches, the major proteins bound to the probe were identified to be tubulin and heat shock protein 27 (Hsp27), and the compound inhibited tubulin polymerization by binding at the colchicine domain. However, the tubulin inhibitory effect of the compound activated the Hsp27 phosphorylation and possibly overrode the direct Hsp27 inhibitory effects, which made it difficult to solely validate the Hsp27 target. Taken together, the compound was a dual ligand of tubulin and Hsp27, inhibited tubulin polymerization, and had the potential to be a class of new chemotherapeutic agents.