Wildfire Smoke Exposure Is Associated with Adverse Respiratory Events under General Anesthesia in At-risk Pediatric Patients.

Background: Increasing wildfire activity worldwide has led to exposure to poor air quality and numerous detrimental health impacts. This study hypothesized an association between exposure to poor air quality from wildfire smoke and adverse respiratory events under general anesthesia in pediatric patients.

Methods: This was a single-center retrospective double-cohort study examining two significant wildfire events in Northern California.

Ring Expansion of 1-Indanones to 2-Halo-1-naphthols as an Entry Point to Gilvocarcin Natural Products.

Herein, we describe a two-step ring expansion of 1-indanones to afford 2-chloro/bromo-1-naphthols (32 examples). The developed method shows broad functional group tolerance, benefits from mild reaction conditions, and enables rapid access to the tetracyclic core of gilvocarcin natural products. The orthogonally functionalized products allow for selective postmodifications as exemplified in the total synthesis of defucogilvocarcin M.

Colonic Epithelial-Derived Selenoprotein P Is the Source for Antioxidant-Mediated Protection in Colitis-Associated Cancer.

Background & Aims: Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context.

Use of Remifentanil for Open in utero Fetal Myelomeningocele Repair Maintains Uterine Relaxation with Reduced Volatile Anesthetic Concentration.

Introduction: Open fetal repair of myelomeningocele (MMC) is an option for prenatally diagnosed spina bifida. Historically, high-dose volatile anesthetic was used for uterine relaxation but is associated with fetal cardiovascular depression. We examined the impact of administering a supplemental remifentanil infusion on the concentration of inhaled anesthetic required for intraoperative uterine relaxation.

Accessing low-oxidation state taxanes: is taxadiene-4(5)-epoxide on the taxol biosynthetic pathway?

We have shown for the first time that taxadiene () can be epoxidised in a regio- and diastereoselective manner to provide taxadiene-4(5)-epoxide () as a single diastereoisomer, and that this epoxide can be rearranged to give taxa-4(20),11(12)-dien-5α-ol (). Furthermore, the epoxide rearranges under acidic conditions to give taxa-4(20),11(12)-dien-5α-ol (), the known bridged ether OCT () and the new oxacyclotaxane (OCT2) . Contrary to previous speculation, taxadiene-4(5)-epoxide () is susceptible to rearrangement when exposed to an iron porphyrin, and these observations justify consideration of epoxide as a chemically competent intermediate on the taxol biosynthetic pathway.

Ezrin Binds to DEAD-Box RNA Helicase DDX3 and Regulates Its Function and Protein Level.

Ezrin is a key regulator of cancer metastasis that links the extracellular matrix to the actin cytoskeleton and regulates cell morphology and motility. We discovered a small-molecule inhibitor, NSC305787, that directly binds to ezrin and inhibits its function. In this study, we used a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS-MS)-based proteomic approach to identify ezrin-interacting proteins that are competed away by NSC305787.

Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists.

A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP <3.5, chrom logD₇.