Total Synthesis of the Diterpenoid (+)â Harringtonolide

Described herein is the first asymmetric total synthesis of (+)â harringtonolide, a natural diterpenoid with an unusual tropone imbedded in a cagelike framework. The key transformations include an intramolecular Dielsâ Alder reaction and a rhodiumâ complexâ catalyzed intramolecular [3+2] cycloaddition to install the tetracyclic core as well as a highly efficient tropone formation.Ever more rings: The first asymmetric total synthesis of the diterpenoid (+)â harringtonolide is described. The key features include an asymmetric transfer hydrogenation, an intramolecular Dielsâ Alder reaction, chemoselective functionalization of an olefin in the presence of an acetylenic group, a rhodiumâ catalyzed intramolecular [3+2] cycloaddition, and efficient formation of the tropone.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137303/1/anie201605879-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137303/2/anie201605879_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137303/3/anie201605879.pd

iTRAQ-based quantitative proteomics analysis identifies host pathways modulated during toxoplasma gondii infection in swine

Toxoplasma gondii is a leading cause of foodborne illness and consumption of undercooked pig meat is a major risk factor for acquiring toxoplasmosis, which causes a substantial burden on society. Here, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify cellular proteins and pathways altered during T. gondii infection in pigs. We also used parallel reaction monitoring-based LC-MS/MS to verify the levels of protein expression of infected spleens and mesenteric lymph nodes (MLNs). At 6 days post-infection (dpi), 156, 391, 170, 292, and 200 differentially expressed proteins (DEPs) were detected in the brain, liver, lung, MLNs and spleen, respectively. At 18 dpi, 339, 351, 483, 388, and 303 DEPs were detected in the brain, liver, lung, MLNs and spleen, respectively. Although proteins involved in immune responses were upregulated in all infected tissues, protein expression signature in infected livers was dominated by downregulation of the metabolic processes. By weighted gene co-expression network analysis, we could further show that all proteins were clustered into 25 co-expression modules and that the pink module significantly correlated with the infection status. We also identified 163 potential anti-T. gondii proteins (PATPs) and provided evidence that two PATPs (HSP70.2 and PDIA3) can reduce T. gondii burden in porcine macrophages in vitro. This comprehensive proteomics analysis reveals new facets in the pathogenesis of T. gondii infection and identifies key proteins that may contribute to the pig’s defense against this infection

A Search for Radio Pulsars in Supernova Remnants Using FAST with One Pulsar Discovered

We report on the results of a search for radio pulsars in five supernova remnants (SNRs) with FAST. The observations were made using the 19-beam receiver in the Snapshot mode. The integration time for each pointing is 10 min. We discovered a new pulsar PSR J1845$-$0306 which has a spin period of 983.6 ms and a dispersion measure of 444.6$\pm$2.0 cm$^{-3}$ pc in observations of SNR G29.6+0.1. To judge the association between the pulsar and the SNR, further verification is needed. We also re-detected some known pulsars in the data from SNRs G29.6+0.1 and G29.7$-$0.3. No pulsars were detected in observations of other three SNRs.Comment: 6 pages, 2 figures, 2 tables published in CP

High-resolution chalcogenide fiber bundles for infrared imaging

An ordered chalcogenide fiber bundle with a high resolution for infrared imaging was fabricated using a stack-and-draw approach. The fiber bundle consisted of about 810,000 single fibers with an As2S3 glass core of 9 μm in diameter and a polyetherimide (PEI) polymer cladding of 10 μm in diameter. The As2S3 fibers showed good transparency in the 1.5–6.5 μm spectral region. It presented a resolution of ~45 lp/mm and a crosstalk of ~2.5%. Fine thermal images of a hot soldering iron tip were delivered through the fiber bundle

Global Transcriptome Profiling of Multiple Porcine Organs Reveals Toxoplasma gondii-Induced Transcriptional Landscapes

© 2019 He, Ma, Wang, Zhang, Li, Zhai, Wang, Elsheikha and Zhu. We characterized the porcine tissue transcriptional landscapes that follow Toxoplasma gondii infection. RNAs were isolated from liver, spleen, cerebral cortex, lung, and mesenteric lymph nodes (MLNs) of T. gondii-infected and uninfected (control) pigs at days 6 and 18 postinfection, and were analyzed using next-generation sequencing (RNA-seq). T. gondii altered the expression of 178, 476, 199, 201, and 362 transcripts at 6 dpi and 217, 223, 347, 119, and 161 at 18 dpi in the infected brain, liver, lung, MLNs and spleen, respectively. The differentially expressed transcripts (DETs) were grouped into five expression patterns and 10 sub-clusters. Gene Ontology enrichment and pathway analysis revealed that immune-related genes dominated the overall transcriptomic signature and that metabolic processes, such as steroid biosynthesis, and metabolism of lipid and carboxylic acid, were downregulated in infected tissues. Co-expression network analysis identified transcriptional modules associated with host immune response to infection. These findings not only show how T. gondii infection alters porcine transcriptome in a tissue-specific manner, but also offer a gateway for testing new hypotheses regarding human response to T. gondii infection

Acetylome analysis of the feline small intestine following Toxoplasma gondii infection

Toxoplasma gondii is a protozoan parasite capable of infecting a large number of warm-blooded animals and causes serious health complications in immunocompromised patients. T. gondii infection of the feline small intestine is critical for the completion of the life cycle and transmission of T. gondii. Protein acetylation is an important posttranslational modification, which plays roles in the regulation of various cellular processes. Therefore, understanding of how T. gondii reprograms the protein acetylation status of feline definitive host can help to thwart the production and spread of T. gondii. Here, we used affinity enrichment and high-resolution liquid chromatography with tandem mass spectrometry to profile the alterations of the acetylome in cat small intestine 10 days after infection by T. gondii Prugniuad (Pru) strain. Our analysis showed that T. gondii induced significant changes in the acetylation of proteins in the cat intestine. We identified 2606 unique lysine acetylation sites in 1357 acetylated proteins. The levels of 334 acetylated peptides were downregulated, while the levels of 82 acetylated peptides were increased in the infected small intestine. The proteins with differentially acetylated peptides were particularly enriched in the bioenergetics-related processes, such as tricarboxylic acid cycle, oxidative phosphorylation, and oxidation-reduction. These results provide the first baseline of the global acetylome of feline small intestine following T. gondii infection and should facilitate further analysis of the role of acetylated protein in the pathogenesis of T. gondii infection in its definitive host

An optimized short‐term steroid therapy for chronic drug‐induced liver injury: A prospective randomized clinical trial

Background and AimsThe use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR.MethodsA randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety.ResultsOf the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed.ConclusionsBoth the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146)

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe