Langston Hess (turnipnapkin75)

Supporting these findings, our in vitro experiments revealed that rTM reduces Ang II-triggered overproduction of sFlt-1 in human trophoblast cells. Moreover, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), well-known key inflammatory mediators in PE pathogenesis, were diminished by rTM. SiRNA knockdown experiments further determined that these processes were directly mediated by HMGB1. Our studies demonstrate that rTM exerts its clinical effect as HMBG1 inhibitor and ameliorates placental dysfunction, which is central to PE pathogenesis. Our findings suggest that rTM could be a promising therapeutic that significantly improve the outcomes of PE patients.We report a series of synthetic, nucleic acid mimics with highly customizable thermodynamic binding to DNA. Incorporation of helix-promoting cyclopentanes into peptide nucleic acids (PNAs) increases the melting temperatures (Tm) of PNA+DNA duplexes by approximately +5°C per cyclopentane. Sequential addition of cyclopentanes allows the Tm of PNA + DNA duplexes to be systematically fine-tuned from +5 to +50°C compared with the unmodified PNA. Containing only nine nucleobases and an equal number of cyclopentanes, cpPNA-9 binds to complementary DNA with a Tm around 90°C. Additional experiments reveal that the cpPNA-9 sequence specifically binds to DNA duplexes containing its complementary sequence and functions as a PCR clamp. An X-ray crystal structure of the cpPNA-9-DNA duplex revealed that cyclopentanes likely induce a right-handed helix in the PNA with conformations that promote DNA binding.Just as eukaryotic circular RNA (circRNA) is a product of intracellular backsplicing, custom circRNA can be synthesized in vitro using a transcription template in which transposed halves of a split group I intron flank the sequence of the RNA to be circularized. Such permuted intron-exon (PIE) constructs have been used to produce circRNA versions of ribozymes, mimics of viral RNA motifs, a streptavidin aptamer, and protein expression vectors for genetic engineering and vaccine development. One limitation of this approach is the obligatory incorporation of small RNA segments (E1 and E2) into nascent circRNA at the site of end-joining. This restriction may preclude synthesis of small circRNA therapeutics and RNA nanoparticles that are sensitive to extraneous sequence, as well as larger circRNA mimics whose sequences must precisely match those of the native species on which they are modelled. In this work, we used serial mutagenesis and in vitro selection to determine how varying E1 and E2 sequences in a thymidylate synthase (td) group I intron PIE transcription template construct affects circRNA synthesis yield. Based on our collective findings, we present guidelines for the design of custom-tailored PIE transcription templates from which synthetic circRNAs of almost any sequence may be efficiently synthesized. Oseltamivir shows effectiveness in reducing influenza-related symptoms, morbidity and mortality. Its prescription remains suboptimal. We aim to describe oseltamivir prescription in confirmed cases of influenza and to identify associated factors. A prospective monocentric observational study was conducted between 1 December 2018 and 30 April 2019. All patients with a virologically confirmed influenza diagnosis were included. Factors associated with oseltamivir prescription were studied. Influenza was confirmed in 755 patients (483 children and 272 adults), of which 188 (25.1%) were hospitalized and 86 (11.4%) had signs of severity. Oseltamivir was prescribed for 452 patients (59.9%), more frequently in children than in adults [329/483 (68.1%) versus 123/272 (45.2%), P < 0.001]. Factors associated with oseltamivir prescription were evaluated in 729 patients (246 adults and 483 children). Patients with at least one risk factor for severe influenza received oseltamivir less frequently (50%, 137/274) than those without risk factors (70