Metal-Free Radical Oxidative Annulation of Ynones with Alkanes To Access Indenones

The benzoyl peroxide (BPO) promoted carboannulation of ynones with alkanes is developed, affording a series of 2-alkyl-3-aryl indenones in moderate to good yields. The procedure involves direct functionalization of alkane C­(sp³)–H and arene C­(sp²)–H bonds under metal-free conditions, providing a favorable approach for indenone synthesis

Systemic and lung cytokine and chemokine levels in LCR and HCR rats infected with <i>S</i>. <i>aureus</i>.

<p>LCR rats (Circles) and HCR rats (Squares) were challenged IV with <i>S</i>. <i>aureus</i> (n = 7/group). Levels of IL-6, IL-10, MIP-2, and 1L-17A were quantified in the serum, BALF, and lung homogenates 48 h after challenge with <i>S</i>. <i>aureus</i>. Compared with infected HCR rats, infected LCR rats had higher levels of IL-6 in plasmas, BALF and lung homogenates (**p = 0.007, **p = 0.0006, and *p = 0.0262, respectively), higher levels of MIP-2 in plasmas and lung homogenates (**p = 0.004 and **p = 0.0006, respectively), and higher levels of IL-17A in lung homogenates (**p = 0.0006). In contrast, compared with infected HCR rats, infected LCR rats had lower levels of IL-10 in plasmas, BALF and lung homogenates (**p = 0.007, ***p = 0.0006, and **p = 0.0041, respectively). The figures show levels of cytokines after subtracting out the values measured in control rats treated with sterile saline from the values measured in rats treated with <i>S</i>. <i>aureus</i> (i.e.: cytokine value shown on Y axis for LCR rats = cytokine level of LCR with <i>S</i>. <i>aureus</i> infection—cytokine level of LCR rat treated with sterile saline, similarly for HCR rats). Data were analyzed using Mann Whitney U tests; results are expressed as median with interquartile range. HCR = high capacity runner; LCR = low capacity runner; BALF = bronchoalveolar lavage fluid; IL = interleukin; MIP = macrophage inflammatory protein.</p

Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During <i>Staphylococcus aureus</i> Infection in Rats with the Metabolic Syndrome

<div><p>Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during <i>Staphylococcus (S</i>.<i>) aureus</i> sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with <i>S</i>. <i>aureus</i> bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung <i>S</i>. <i>aureus</i> counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During <i>S</i>. <i>aureus</i> bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.</p></div

Bacterial levels in rats with <i>S</i>. <i>aureus</i> bacteremia.

<p>LCR rats (Circles) and HCR rats (Squares) were challenged IV with <i>S</i>. <i>aureus</i> (n = 7/group). 48 h later levels of <i>S</i>. <i>aureus</i> were significantly higher in the blood, BALF, and lung homogenates of LCR as compared with HCR rats (*p = 0.041, **p = 0.0006, and *p = 0.038, respectively, Mann Whitney U tests). Results are expressed as median with interquartile range. HCR = high capacity runner; LCR = low capacity runner; BALF = bronchoalveolar lavage fluid; CFU = colony-forming units.</p

Lung permeability, edema and histology in LCR and HCR rats infected with <i>S</i>. <i>aureus</i>.

<p>Protein level in the BALF, lung wet-dry weight ratios, and lung histology were assessed 48 h after LCR and HCR rats were challenged IV with <i>S</i>. <i>aureus</i> (n = 7/group). (A) Compared with infected HCR rats (Squares), infected LCR rats (Circles) had higher levels of BALF protein and higher lung wet-dry weight ratios (***p = 0.0006 and *p = 0.0379, respectively, Mann Whitney U tests). Results are expressed as median with interquartile range. The values shown in the figures represent the BALF protein and lung wet-dry ratios after subtracting out the values in control rats treated with sterile saline from the levels measured in rats treated with <i>S</i>. <i>aureus</i> (i.e.: BALF protein or lung wet-dry ratio value shown on Y axis for LCR rats = BALF protein or lung wet-dry ratio of LCR with <i>S</i>. <i>aureus</i> infection—BALF protein or lung wet-dry ratio of LCR rat treated with sterile saline, similarly for HCR rats). (B) H & E staining of lung sections demonstrated augmentation of inflammatory cell influx, blood, edema, and thickening of the lung interstitium in LCR rats as compared with HCR rats (40-fold magnification, scale bar = 40 μm). HCR = high capacity runner; LCR = low capacity runner. BALF = bronchoalveolar lavage fluid.</p

The Benzoyl Peroxide Promoted Dual C–C Bond Formation via Dual C–H Bond Cleavage: α‑Phenanthridinylation of Ether by Isocyanide

The benzoyl peroxide-promoted α-phenanthridinylation of ether by isocyanide is developed, proceeding through dual C–H bond cleavage and dual C–C bond formation. The procedure tolerates a series of functional groups, such as methyl, fluoro, chloro, acetyl, methoxy carbonyl, cyano, and trifluoromethyl. Thus, it represents a facile pathway leading to 6-substituted phenanthridine derivatives. The addition of radical to the isonitrile followed by a radical aromatic cyclization is involved in this transformation