Gold-Catalyzed Cascade Reaction of Diynamides with Allylic Alcohols: A Versatile Platform to Allenamide, 2-Aminofuran and Bridged [2.2.2]Octadiene Derivatives.

Transition metal-catalyzed divergent synthesis through alternation of the catalyst is appealing, as it provides an operationally simple way to access different valuable products, while using the same reactants as starting materials. Herein, a gold-catalyzed cascade reaction of conjugated diynamides with allylic alcohols is described. By variation of the catalysts, substituted allenes and furans could be obtained selectively. Mechanistic studies indicate that, after the addition of allylic alcohol to gold-activated diynamide, a [3,3]-sigmatropic rearrangement would take place and lead to the formation of a common reactive intermediate, which would further convert to the final products selectively. Further variation of the structure of diynamides has unveiled an additional reaction sequence involving intramolecular Himbert arene/allene Diels-Alder cycloaddition to afford a series of dearomatized products bearing bicyclo[2,2,2]octadiene core.

Sex-specific non-linear associations between body mass index and impaired pulmonary ventilation function in a community-based population: Longgang COPD study.

Aim: To investigate the prevalence of pulmonary airflow limitation and its association with body mass index (BMI) in a community-based population in Shenzhen, China. Methods: Study participants were recruited from Nanlian Community in Shenzhen, China, and spirometry was performed to assess lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and FEV1 divided by predicted value. Pulmonary airflow limitation was determined by the Chinese Guideline of Pulmonary Function Examination. Multivariable logistic regression models were used to examine the association between BMI and pulmonary airflow limitation. Age, sex, educational attainment, occupation, and current cigarette smoking were used as potential confounders. Results: Of the 1206 participants, 612 (50.7%) were men and 594 (49.3%) were women with the average age being 53.7 years old. After adjusting for age, sex, educational attainment, occupation, and current cigarette smoking, higher BMI was associated with lower odds (odds ratio: 0.98, 95% confidence interval: 0.97, 0.99) of pulmonary airflow limitation by assuming a linear relationship. Further investigation of the interaction terms, we found that the magnitudes of the associations differed in men and women. A U-shaped relationship was observed in women, while the association was almost linear in men. Conclusion: The relationship between BMI and pulmonary airflow limitation was U-shaped in women and linear in men.

Alkyne Insertion Enabled Vinyl to Acyl 1,5-Palladium Migration: Rapid Access to Substituted 5-Membered-Dihydrobenzofurans and Indolines.

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C-H bond. Compared with relatively extensive exploited 1,4-palladium migration process, the relevant 1,5-Pd/H shift was far less investigated. We herein report a novel 1,5-Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5-membered-dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5-palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5-palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate.

Resistance optimization of a coil with substrate and design of a high-power-density coupler for wireless power transfer.

Wireless power transfer (WPT) technology has been popularized due to its convenience, safety, and unmanned nature. To improve the transmission performance of couplers and reduce the magnetic field, the designers of such couplers often adopt a combination of coils and substrates: however, the non-ferromagnetic substrate often leads to the enhancement of coil equivalent resistance and the decrease of the efficiency of a WPT system. In the present work, the effect of a substrate on coil equivalent resistance is evaluated by finite element simulation. The effects of the distance between a substrate and a coil and the number of turns of coil on the equivalent resistance of coils are studied. Based on the calculation method of alternating current resistance for Litz-wire, the equivalent resistance reduction method involving use of a coil with substrates is proposed to significantly reduce equivalent resistance of the coil with its substrate. A high-power-density coupler is designed based on the above method. The power densities of a transmitting coil and a receiving coil are only 0.542 W/cm 3 and 0.81 W/cm 3 respectively. When the transmission distance is 200 mm, a power transmission of 3.61 kW is realized, and the efficiency of the coupler and system reaches 94.61% and 92.56%, respectively.

Divergent Access to Polycyclic N-Heterocyclic Compounds through Büchner-Type Dearomatization Enabled Cycloisomerization of Diynamides under Gold Catalysis.

Catalytic dearomatization has been considered as a valuable approach to convert readily accessible flat molecules to products with three-dimensional frameworks. Herein, an unprecedented gold-catalyzed oxidative Büchner-type cyclopropanation is described that enables the cycloisomerization of diynamides. By variation of the position of substituents on the phenyl ring, a variety of fused N-heterocyclic products with challenging structural skeletons were obtained divergently.

Palladium-Catalyzed Three-Component Selective Aminoallylation of Diazo Compounds.

We describe a Xantphos-containing dinuclear palladium complex-enabled geminal aminoallylation of diazocarbonyl compounds, which selectively provides a range of quaternary α-amino esters. Direct N-H insertion, allylic alkylation of amino nucleophiles, and diene formation were not observed under standard conditions. Mechanistic studies indicated that a relayed pathway via allylation of the N-H insertion product or [2,3]-sigmatropic rearrangement of an ylide intermediate was unlikely.

Efficient access to 1,3,4-trisubstituted pyrroles via gold-catalysed cycloisomerization of 1,5-diynes.

A gold-catalysed cycloisomerization of 1,5-diynes is described, which offers a selective approach to access 1,3,4-trisubstituted pyrroles. In this reaction, the cationic gold catalyst activates the ynamide moiety, initiating the cycloisomerization to produce the pyrrole core, and H2O acts as an external nucleophile to trap the vinyl cationic species, thus leading to the formation of 1,3,4-trisubstituted pyrroles with high selectivity.

Toward Robust Non-Intrusive Load Monitoring via Probability Model Framed Ensemble Method.

As a pivotal technological foundation for smart home implementation, non-intrusive load monitoring is emerging as a widely recognized and popular technology to replace the sensors or sockets networks for the detailed household appliance monitoring. In this paper, a probability model framed ensemble method is proposed for the target of robust appliance monitoring. Firstly, the non-intrusive load disaggregation-oriented ensemble architecture is presented. Then, dictionary learning model is utilized to formulate the individual classifier, while the sparse coding-based approach is capable of providing multiple solutions under greedy mechanism. Furthermore, a fully probabilistic model is established for combined classifier, where the candidate solutions are all labelled with probability scores and evaluated via two-stage decision-making. The proposed method is tested on both low-voltage network simulator platform and field measurement datasets, and the results show that the proposed ensemble method always guarantees an enhancement on the performance of non-intrusive load disaggregation. Besides, the proposed approach shows high flexibility and scalability in classification model selection. Therefore, by initializing the architecture and approach of ensemble method-based NILM, this work plays a pioneer role in using ensemble method to improve the robustness and reliability of non-intrusive appliance monitoring.

An Enhanced Ensemble Approach for Non-Intrusive Energy Use Monitoring Based on Multidimensional Heterogeneity.

Acting as a virtual sensor network for household appliance energy use monitoring, non-intrusive load monitoring is emerging as the technical basis for refined electricity analysis as well as home energy management. Aiming for robust and reliable monitoring, the ensemble approach has been expected in load disaggregation, but the obstacles of design difficulty and computational inefficiency still exist. To address this, an ensemble design integrated with multi-heterogeneity is proposed for non-intrusive energy use disaggregation in this paper. Firstly, the idea of utilizing a heterogeneous design is presented, and the corresponding ensemble framework for load disaggregation is established. Then, a sparse coding model is allocated for individual classifiers, and the combined classifier is diversified by introducing different distance and similarity measures without consideration of sparsity, forming mutually heterogeneous classifiers. Lastly, a multiple-evaluations-based decision process is fine-tuned following the interactions of multi-heterogeneous committees, and finally deployed as the decision maker. Through verifications on both a low-voltage network simulator and a field measurement dataset, the proposed approach is demonstrated to be effective in enhancing load disaggregation performance robustly. By appropriately introducing the heterogeneous design into the ensemble approach, load monitoring improvements are observed with reduced computational burden, which stimulates research enthusiasm in investigating valid ensemble strategies for practical non-intrusive load monitoring implementations.

Divergent synthesis of 1,3,5-tri and 1,3-disubstituted pyrazoles under transition metal-free conditions.

Pyrazole cores are common structural motifs existing in various agrochemicals and pharmaceuticals. Herein, a transition metal-free, three-component reaction of arylaldehydes, ethyl acrylate and N-tosylhydrazones is described, which leads to the formation of 1,3,5-trisubstituted and 1,3-disubstituted pyrazoles divergently under slightly different conditions.

A Modular Approach to Dibenzo-fused ϵ-Lactams: Palladium-Catalyzed Bridging-C-H Activation.

Tricyclic ring systems possessing a dibenzo structure joined to a seven-membered heterocyclic ring frequently show important biological activities. However, a modular approach to these molecules based on efficient intermolecular reaction of readily available chemicals is lacking. Herein, an unprecedented palladium-catalyzed formal [4+3] annulation for modular construction of these tricyclic systems is described. This reaction features easily accessible reactants (o-haloarylaldehydes and N-tosylhydrazones), broad substrate scope, and excellent functional group compatibility. The synthetic potential is demonstrated by the easy scale-up reactions, late-stage modification of complex molecules, and collective synthesis of bioactive molecules and approved drugs.

Facile access to 2,2-diaryl 2H-chromenes through a palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones.

A palladium-catalyzed cascade reaction of ortho-vinyl bromobenzenes with N-tosylhydrazones has been developed, which provides a facile approach to 2,2-disubstituted 2H-chromenes. The migration of palladium from the aryl to vinyl position is crucial, as the in situ produced vinyl palladium intermediate could further react with diazo compounds to generate the reactive species for the sequential annulation.

Understanding the Chemoselectivity in Palladium-Catalyzed Three-Component Reaction of o-Bromobenzaldehyde, N-Tosylhydrazone, and Methanol.

To understand the ligand-controlled palladium-catalyzed coupling of o-bromobenzaldehyde, N-tosylhydrazone, and methanol to give methyl 2-benzylbenzoic ester or methyl ether, we herein investigated the mechanisms which account for how C-C and C-O bonds are formed and why bidentate dppf/dppb ligands afford ester, whereas P(o-tolyl)3 ligand gives ether. The ester chemoselectivity of the bidentate ligands is attributed to the strong electron-donating effect that disfavors the C,Br-reductive elimination of the coupling intermediate of o-bromobenzaldehyde and N-tosylhydrazone.

Gold-Catalyzed Oxidative Cascade Cyclization of 1,3-Diynamides: Polycyclic N-Heterocycle Synthesis via Construction of a Furopyridinyl Core.

A facile and practical approach to construct a furopyridinyl motif through a gold-catalyzed cascade cyclization of easily accessible diynamides is described. This strategy offers a straightforward approach to furo[2,3-c]isoquinoline and 6H-furo[3',2':5,6]pyrido[3,4-b]indole derivatives. The reaction could build up four new bonds and two additional heteroaromatic rings via a single operation. The heterocyclic products show promising blue luminous performance with fluorescence quantum yields up to 75%.

Palladium-Catalyzed Three-Component Coupling Reaction of o-Bromobenzaldehyde, N-Tosylhydrazone, and Methanol.

A ligand-controlled palladium-catalyzed three-component reaction of o-bromobenzaldehyde, N-tosylhydrazone, and methanol is described. This reaction uses readily available compounds as starting materials while displaying a broad substrate scope and good functional group compatibility.

Easy access to medium-sized lactones through metal carbene migratory insertion enabled 1,4-palladium shift.

Reactions that efficiently construct medium-sized lactones are significant, as they overcome the unfavorable entropic factor and transannular interactions for ring closure, and the lactones produced are common structural motifs recurring in many biologically active compounds. Herein, we describe a valuable strategy for medium-sized lactone synthesis by accomplishing site-selective C-H bond functionalization via a palladium carbene migratory insertion enabled 1,4-palladium shift. The overall process achieves the formal dimerization of two readily available benzaldehyde derivatives, providing value-added products medium-sized lactones. Our method is amenable to late-stage modification of approved drugs and other complex molecules. Mechanistic studies including deuterium-labeling experiments and DFT calculation shed light on the reaction pathways.

Filter-based measurement of light absorption by brown carbon in PM2.5 in a megacity in South China.

Carbonaceous aerosols represent an important nexus between air pollution and climate change. Here we collected filter-based PM2.5 samples during summer and autumn in 2015 at one urban and two rural sites in Guangzhou, a megacity in southern China, and got the light absorption by black carbon (BC) and brown carbon (BrC) resolved with a DRI Model 2015 multi-wavelength thermal/optical carbon analyzer apart from determining the organic carbon (OC) and elemental carbon (EC) contents. On average BrC contributed 12-15% of the measured absorption at 405nm (LA405) during summer and 15-19% during autumn with significant increase in the LA405 by BrC at the rural sites. Carbonaceous aerosols, identified as total carbon (TC), yielded average mass absorption efficiency at 405nm (MAE405) that were approximately 45% higher in autumn than in summer, an 83% increase was noted in the average MAE405 for OC, compared with an increase of only 14% in the average MAE405 for EC. The LA405 by BrC showed a good correlation (p<0.001) with the ratios of secondary OC to PM2.5 in summer. However, this correlation was poor (p>0.1) in autumn, implying greater secondary formation of BrC in summer. The correlations between levoglucosan (a marker of biomass burning) and the LA405 by BrC were significant during autumn but insignificant during summer, suggesting that the observed increase in the LA405 by BrC during autumn in rural areas was largely related to biomass burning. The measurements of light absorption at 550nm presented in this study indicated that the use of the IMPROVE algorithm with an MAE value of 10m2/g for EC to approximate light absorption may be appropriate in areas not strongly affected by fossil fuel combustion; however, this practice would underestimate the absorption of light by PM2.5 in areas heavily affected by vehicle exhausts and coal burning.

Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of hepatocellular carcinoma.

Exosomal microRNAs have recently been studied as the potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and Western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 was further analyzed and significantly higher in HCC than LC and normal control (NC) groups (P < 0.001), but not different from chronic hepatitis group (P > 0.05). The receiver operating characteristic curve was used to evaluate the diagnostic performance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95% confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha-fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607-0.803). Binary logistic regression was adopted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a, and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggest that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.

Palladium-Catalyzed Intermolecular Acylation of Aryl Diazoesters with ortho-Bromobenzaldehydes.

In this work, we describe a palladium-catalyzed intermolecular O acylation of α-diazoesters with ortho-bromobenzaldehydes. The C(sp2 )-H bond activation of the aldehyde is enabled by migratory insertion of a palladium carbene intermediate. The diazoesters act as modular three-atom units to build up key seven-membered palladacycles, which are transformed into a variety of isocoumarin derivatives upon reductive elimination. Mechanistic experiments and DFT calculations provide insight into the reaction pathway.

Dynamic changes in serum cytokine levels and their clinical significance in predicting acute GVHD.

To explore the clinical significance of cytokines and biochemical tests in acute graft-versus-host disease (aGVHD), we detected the concentrations of 8 cytokines and 19 conventional biochemical markers in the sera of aGVHD and non-GVHD patients throughout the process of allogeneic hematopoietic stem cell transplantation and the onset of aGVHD. Predictive models were then established using the 27 indices, and models were verified by a prospective trial. The 27 indices showed significant differences between aGVHD patients and non-GVHD control subjects (two-tailed p<0.05) prior to transplantation and before the onset of aGVHD. Our models, established by binary logistic regression on days +7 and +14, showed a significant absolute capacity of predicting grade 2∼4 aGVHD with positive and negative predictive values of at least 70%. Our data showed that the progression of aGVHD could induce dynamic changes in the levels of serum cytokines and biochemical markers. Because most of these tests were less specific for aGVHD, these changes were easily neglected in clinical work. However, by combining cytokine and biochemical tests, the established prediction model can greatly improve the ability of these biomarkers to predict the development of aGVHD one or two weeks earlier.