Synthesis of hydroxyfatty esters by sequential epoxidation-hydrogenolysis: Solvent effects

The tandem/sequential combination of epoxidation and hydrogenolysis for unsaturated fatty esters is not straightforward, due to incompatibility problems with the impurities present or generated in the used solvents. The chlorinated impurities in alpha, alpha, alpha-trifluorotoluene leads to the formation of important amounts of chlorohydrins by HCl formation in the hydrogenolysis step. The use of trifluoroethanol (TFE) in the epoxidation step produces trifluoroacetic acid traces by oxidation, responsible for the opening of the epoxide with water and TFE. The solvent of choice was finally isobutyl acetate, which gathers the required physicochemical properties, with 85 % yield of hydroxystearates from methyl oleate in a sequential process

An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice

<p>Abstract</p> <p>Background</p> <p>Despite its reported pro-inflammatory activity, cyclooxygenase (COX)-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA)-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM)-sensitized mice in which we mimicked altered regulation of COX-2.</p> <p>Methods</p> <p>Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production.</p> <p>Results</p> <p>We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE₂in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR) to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged.</p> <p>Conclusion</p> <p>Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.</p

The United States and the PRC: Macroeconomic Imbalances and Economic Diplomacy

This paper explores the ways in which macroeconomic imbalances have driven policy discussions between the United States (US) and People's Republic of China (PRC) in the last decade. The PRC's current account surplus, its growing foreign exchange reserves, and its shifting policies on exchange rate adjustment have become a central preoccupation of US trade policy. The paper considers the evolving political economy of the US policy stance and of the PRC's response; it assesses the opportunity costs of an approach that has sometimes focused on the exchange rate to the exclusion of other issues; and it explores the ramifications for economic governance in the short- and medium-run. The paper finds that there has been ample mutual misunderstanding between the US and the PRC in their economic arguments; that the momentous debates have the potential to severely impair the institutions of global economic governance; and that there is likely to be an important race between economic and demographic forces that will naturally redress the imbalances and the political imperatives for each country to stand tough and fight

Hypercapnia alters stromal-derived Wnt production limiting β-catenin signaling and proliferation in alveolar type 2 cells

Persistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 pneumonia, low tidal volumes to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here - using a mouse model of hypercapnia exposure, cell lineage tracing, spatial transcriptomics, and 3D cultures - we show that hypercapnia limits β-catenin signaling in alveolar type II (AT2) cells, leading to their reduced proliferative capacity. Hypercapnia alters expression of major Wnts in PDGFRα+ fibroblasts from those maintaining AT2 progenitor activity toward those that antagonize β-catenin signaling, thereby limiting progenitor function. Constitutive activation of β-catenin signaling in AT2 cells or treatment of organoid cultures with recombinant WNT3A protein bypasses the inhibitory effects of hypercapnia. Inhibition of AT2 proliferation in patients with hypercapnia may contribute to impaired lung repair after injury, preventing sealing of the epithelial barrier and increasing lung flooding, ventilator dependency, and mortality.Fil: Dada, Laura Andrea. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Welch, Lynn C.. Northwestern University; Estados UnidosFil: Magnani, Natalia Daniela. Northwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ren, Ziyou. Northwestern University; Estados UnidosFil: Han, Hyebin. Northwestern University; Estados UnidosFil: Brazee, Patricia L.. Northwestern University; Estados UnidosFil: Celli, Diego. Northwestern University; Estados UnidosFil: Flozak, Annette S.. Northwestern University; Estados UnidosFil: Weng, Anthea. Northwestern University; Estados UnidosFil: Herrerias, Mariana Maciel. Northwestern University; Estados UnidosFil: Kryvenko, Vitalii. Justus Liebig Universitat Giessen.; AlemaniaFil: Vadász, István. Justus Liebig Universitat Giessen.; AlemaniaFil: Runyan, Constance E.. Northwestern University; Estados UnidosFil: Abdala Valencia, Hiam. Northwestern University; Estados UnidosFil: Shigemura, Masahiko. Northwestern University; Estados UnidosFil: Casalino Matsuda, S. Marina. Northwestern University; Estados UnidosFil: Misharin, Alexander V.. Northwestern University; Estados UnidosFil: Budinger, G. R. Scott. Northwestern University; Estados UnidosFil: Gottardi, Cara J.. Northwestern University; Estados UnidosFil: Sznajder, Jacob I.. Northwestern University; Estados Unido