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Three-component C–H bond additions across two different coupling partners remain underdeveloped. Herein, we report the first three-component RhIII-catalyzed C–H bond additions to a wide range of dienes and aldehydes. Our method constitutes a complementary access with Ellman's CoIII-catalytic system to homoallylic alcohols. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) has the capacity to regulate systemic metabolism through the secretion of signaling lipids. N6-methyladenosine (m 6 A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. In this study, we demonstrate that the absence of m 6 A methyltransferase-like 14 (METTL14), modifies the BAT secretome to initiate inter-organ communication to improve systemic insulin sensitivity. Importantly, these phenotypes are independent of UCP1-mediated energy expenditure and thermogenesis. Using lipidomics, we identified prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as M14 KO -BAT-secreted insulin sensitizers. Notably, circulatory PGE2 and PGF2a levels are inversely correlated with insulin sensitivity in humans. Furthermore, in vivo administration of PGE2 and PGF2a in high-fat diet-induced insulin-resistant obese mice recapitulates the phenotypes of METTL14 deficient animals. PGE2 or PGF2a improves insulin signaling by suppressing the expression of specific AKT phosphatases. Mechanistically, METTL14-mediated m 6 A installation promotes decay of transcripts encoding prostaglandin synthases and their regulators in human and mouse brown adipocytes in a YTHDF2/3-dependent manner. Taken together, these findings reveal a novel biological mechanism through which m 6 A-dependent regulation of BAT secretome regulates systemic insulin sensitivity in mice and humans., Highlights: Mettl14 KO -BAT improves systemic insulin sensitivity via inter-organ communication; PGE2 and PGF2a are BAT-secreted insulin sensitizers and browning inducers;PGE2 and PGF2a sensitize insulin responses through PGE2-EP-pAKT and PGF2a-FP-AKT axis; METTL14-mediated m 6 A installation selectively destabilizes prostaglandin synthases and their regulator transcripts; Targeting METTL14 in BAT has therapeutic potential to enhance systemic insulin sensitivity.

Methods for the precise detection and quantification of RNA modifications are critical to uncover functional roles of diverse RNA modifications. The internal m 7 G modification in mammalian cytoplasmic tRNAs is known to affect tRNA function and impact embryonic stem cell self-renewal, tumorigenesis, cancer progression, and other cellular processes. Here, we introduce m 7 G-quant-seq, a quantitative method that accurately detects internal m 7 G sites in human cytoplasmic tRNAs at single-base resolution. The efficient chemical reduction and mild depurination can almost completely convert internal m 7 G sites into RNA abasic sites (AP sites). We demonstrate that RNA abasic sites induce a mixed variation pattern during reverse transcription, including G → A or C or T mutations as well as deletions. We calculated the total variation ratio to quantify the m 7 G modification fraction at each methylated site. The calibration curves of all relevant motif contexts allow us to more quantitatively determine the m 7 G methylation level. We detected internal m 7 G sites in 22 human cytoplasmic tRNAs from HeLa and HEK293T cells and successfully estimated the corresponding m 7 G methylation stoichiometry. m 7 G-quant-seq could be applied to monitor the tRNA m 7 G methylation level change in diverse biological processes.

The synthesis of silacycles is highly appealing due to their important applications in organic synthesis, medicinal chemistry, and materials chemistry. However, sila-tetralins and sila-benzosuberanes are surprisingly under-represented due to a lack of general methods to access these compounds. We successfully developed a Pd-catalyzed strain-release silicon-based cross-coupling as an unprecedented ring-expansion method, which constitutes a general route for preparing diverse sila-tetralins and sila-benzosuberanes., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the effects of a new anticoagulant, annexin V derivative (AND) on anticoagulation and antithrombosis., Methods: High and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bolus injections followed by half the respective AND doses by iv infusion over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was put into femoral artery to induce endothelial denudation 15 min after IV bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The femoral arteries were collected and the thrombi were stripped off for measuring their lengths, wet and dry weights., Results: Anticoagulation parameters: APTT at 15 min after iv bolus in AND group was significantly longer than that in group 4 (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3 were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The dry weight in high-dose AND group was remarkably lighter than that in low-dose group (P = 0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4 (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group than in group 4 (P < 0.05), but not in 3., Conclusion: AND is an effective anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs at 15 min after IV bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.