Socially-mediated changes in brain epigenome in the fire ant

Herein, we report a robust way for the formation of biodegradable poly(ethylene glycol)-block-poly(e-caprolactone) (PEG-b-PCL) polymersomes, via direct hydration of a highly concentrated block copolymer/oligo(ethylene glycol) solution. Polymersomes with variable membrane thickness were formed under relatively mild conditions in a short time, by changing the hydrophobic block length. Plunge freezing followed by cryo transmission electron microscopy (Cryo-TEM) was utilized to visualize the morphology of newly-formed polymersomes in their native condition. An MTT cytotoxicity study showed that the as-prepared polymersomes have good biocompatibility to hCMEC/D3 brain endothelial cells. As this method does not involve the use of small molecular organic solvent, sonication or freeze-thawing steps, it can offer the opportunity to form biodegradable polymersomes on-site. The work may facilitate the bench-to-bedside translation of biodegradable polymersomes as robust drug nanocarriers

Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial

Objectives: To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs). Methods: Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period. Results: A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib. Conclusion: Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib.</p