The selective radical/radical cross-coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper-catalyzed radical/radical C(sp 3)-H/P-H cross-coupling has been developed. It provides a radical/radical cross-coupling in a selective manner. This work offers a simple way toward β-ketophosphonates by oxidative coupling of aryl ketone o-acetyloximes with phosphine oxides using CuCl as catalyst and PCy3 as ligand in dioxane under N2 atmosphere at 130 °C for 5 h, and yields ranging from 47% to 86%. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o-acetyloximes generates iminium radicals, which could isomerize to α-sp(3) -carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o-acetyloximes and phosphine oxides were suitable for this transformation.

Remodelling of M2 and M3 receptors is not associated with AF, but with the dilated left atrium.

Leukemia stem cells (LSCs) are regarded as the origins and key therapeutic targets of leukemia, but limited knowledge is available on the key determinants of LSC ‘stemness’. Using single-cell RNA-seq analysis, we identify a master regulator, SPI1, the LSC-specific expression of which determines the molecular signature and activity of LSCs in the murine Pten-null T-ALL model. Although initiated by PTEN-controlled β-catenin activation, Spi1 expression and LSC ‘stemness’ are maintained by a β-catenin-SPI1-HAVCR2 regulatory circuit independent of the leukemogenic driver mutation. Perturbing any component of this circuit either genetically or pharmacologically can prevent LSC formation or eliminate existing LSCs. LSCs lose their ‘stemness’ when Spi1 expression is silenced by DNA methylation, but Spi1 expression can be reactivated by 5-AZ treatment. Importantly, similar regulatory mechanisms may be also present in human T-ALL.

Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability. Moreover, MD1-KO-AB cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca2+ leak, reduced Ca2+ transient amplitude and SR Ca2+ content, decreased SR Ca2+-ATPase2 expression, and increased phospholamban and Na+/Ca2+-exchanger 1 protein expression. Mechanistically, the adverse effects of MD1 deletion on LV remodelling were related to hyperactivated CaMKII signalling and increased impairment of intracellular Ca2+ homeostasis, whereas the increased electrophysiological instability was partly attributed to exaggerated prolongation of cardiac repolarisation, decreased action potential duration alternans threshold, and increased diastolic SR Ca2+ leak. Therefore, our study on MD1 could provide new therapeutic strategies for preventing/treating heart failure.

The observed surface energy balance fluxes are essential to improve model forecasting ability but such data are scarce for subtropical cities and urban areas with tall buildings. One year of eddy covariance flux data for an area within Shanghai with a wide range of building heights (8-150 m, mean by direction) are analysed by wind direction. Consideration is given to how to distinguish between local-and micro-scale fluxes. At the local-scale, median daily peaks of sensible heat flux occur in the early afternoon (winter: 87 W m −2 , spring: 205 W m −2 , summer: 292 W m −2 , autumn: 135 W m −2 ). The latent heat flux is small in winter (median daily maxima 21 W m −2 ) and slightly larger in spring, summer and autumn (49, 65, 49 W m −2 , respectively). The monthly mean daytime Bowen ratio under all-sky conditions ranges from 2 to 4.7. At this site, with predominately impervious surface (85% buildings/pavement, 14% vegetation), the enhancement of evaporation following rainfall usually lasts for about 12 h. Consistently larger Bowen ratios at the micro-scale than the local-scale are attributed to roughness effects and the impact of extensive areas of dry walls. The daily median CO 2 flux is dominated by traffic emissions, with two peaks associated with morning and evening rush hours. The data provide insights into urban surface controls on momentum, energy and carbon dynamics, with implications for urban planning strategies in the context of rapid global urbanization and climate change.

Chemical cross-linking of proteins coupled with mass spectrometry analysis (CXMS) is widely used to study protein-protein interactions (PPI), protein structures, and even protein dynamics. However, structural information provided by CXMS is still limited, partly because most CXMS experiments use lysine-lysine (K-K) cross-linkers. Although superb in selectivity and reactivity, they are ineffective for lysine deficient regions. Herein, we develop aromatic glyoxal cross-linkers (ArGOs) for arginine-arginine (R-R) cross-linking and the lysine-arginine (K-R) cross-linker KArGO. The R-R or K-R cross-links generated by ArGO or KArGO fit well with protein crystal structures and provide information not attainable by K-K cross-links. KArGO, in particular, is highly valuable for CXMS, with robust performance on a variety of samples including a kinase and two multi-protein complexes. In the case of the CNGP complex, KArGO cross-links covered as much of the PPI interface as R-R and K-K cross-links combined and improved the accuracy of Rosetta docking substantially.

Building change detection is important for urban area monitoring, disaster assessment and updating geo-database. 3D information derived from image dense matching or airborne light detection and ranging (LiDAR) is very effective for building change detection. However, combining 3D data from different sources is challenging, and so far few studies have focused on building change detection using both images and LiDAR data. This study proposes an automatic method to detect building changes in urban areas using aerial images and LiDAR data. First, dense image matching is carried out to obtain dense point clouds and then co-registered LiDAR point clouds using the iterative closest point (ICP) algorithm. The registered point clouds are further resampled to a raster DSM (Digital Surface Models). In a second step, height difference and grey-scale similarity are calculated as change indicators and the graph cuts method is employed to determine changes considering the contexture information. Finally, the detected results are refined by removing the non-building changes, in which a novel method based on variance of normal direction of LiDAR points is proposed to remove vegetated areas for positive building changes (newly building or taller) and nEGI (normalized Excessive Green Index) is used for negative building changes (demolish building or lower). To evaluate the proposed method, a test area covering approximately 2.1 km 2 and consisting of many different types of buildings is used for the experiment. Results indicate 93% completeness with correctness of 90.2% for positive changes, while 94% completeness with correctness of 94.1% for negative changes, which demonstrate the promising performance of the proposed method.

Increased NADPH oxidase activity is found in both experimental and clinical HF. Here, we investigated the effects and mechanisms of NADPH oxidase inhibition on cardiac function in rabbits with HF. HF was induced by combined volume and pressure overload. Rabbits with HF or sham operation were randomized to orally receive apocynin, an inhibitor of NADPH oxidase (15 mg per day) or placebo for 8 weeks. Echocardiography was performed to examine the cardiac function and structure of the rabbits. Cardiac fibrosis was evaluated by masson's trichrome staining. The transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) expression were measured by real-time PCR. The expression of SERCA2a and phospholamban (PLB) was detected by reverse transcription-polymerase chain reaction and Western Blot. SERCA2a activity was evaluated by measuring the Pi liberated from ATP hydrolysis. Rabbits with HF exhibited cardiac dysfunction and fibrosis. These changes were associated with significant increases in myocardial NADPH oxidase activity and oxidative stress. Compared with sham-operated rabbits, the TGF-β, CTGF, MMP-2, and MMP-9 mRNA expression significantly increased, the expression of SERCA2a and PLB dramatically decreased, and the SERCA2a activity was lower in HF rabbits. Apocynin reduced NADPH oxidase activity and oxidative stress, decreased TGF-β, CTGF, MMP-2, and MMP-9 expression, attenuated cardiac fibrosis, increased SERCA2a and PLB expression, restored SERCA2a activity, and thereby ameliorated cardiac dysfunction. Thus, chronic NADPH oxidase inhibition ameliorated cardiac dysfunction by decreasing cardiac fibrosis and preserving SERCA2a expression and activity.