The palladium‐catalyzed asymmetric carboamination reaction is one of the most significant transformations in organic chemistry. Herein, we report the first palladium‐catalyzed asymmetric ...alleneamination of β,γ‐unsaturated hydrazones with propargylic acetates. This protocol enables the efficient installation of various multisubstituted allene groups onto dihydropyrazoles in good yields with excellent enantioselectivities. The chiral sulfinamide phosphine ligand Xu‐5 exhibits highly efficient stereoselective control in this protocol. The salient features of this reaction include the readily available starting materials, a broad substrate scope, an easy scale‐up, mild reaction conditions and versatile transformations.
A new robust palladium‐catalyzed enantioselective alleneamination reaction of β,γ‐unsaturated hydrazones with propargylic acetates is described. The salient features of this reaction include general substrate scope, good functional group tolerance, good yields and high enantioselectivities.
The initiation mechanism of debris flow is regarded as the key step in understanding the debris- flow processes of occurrence, development and damage. Moreover, migration, accumulation and blocking ...effects of fine particles in soil will lead to soil failure and then develop into debris flow. Based on this hypothesis and considering the three factors of slope gradient, rainfall duration and rainfall intensity, 16 flume experiments were designed using the method of orthogonal design and completed in a laboratory. Particle composition changes in slope toe, volumetric water content, fine particle movement characteristics and soil failure mechanism were analyzed and understood as follows： the soil has complex, random and unstable structures, which causes remarkable pore characteristics of poor connectivity, non-uniformity and easy variation. The major factors that influence fine particle migration are rainfall intensity and slope. Rainfall intensity dominates particle movement, whereby high intensity rainfall induces a large number of mass movement and sharp fluctuation, causing more fine particles to accumulate at the steep slope toe. The slope toe plays an important role in water collection and fine particle accumulation. Both fine particle migration and coarse particle movement appears similar fluctuation. Fine particle migration is interrupted in unconnected pores, causing pore blockage and fine particle accumulation, which then leads to the formation of a weak layer and further soil failure or collapses. Fine particle movement also causes debris flow formation in two ways： movement on the soil surface and migration inside the soil. The results verify the hypothesis that the function of fine particle migration in soil failure process is conducive for further understanding the formation mechanism of soil failure and debris flow initiation.
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•Seven deep eutectic solvents were prepared and applied in corn stover (CS) pretreatment.•ChCl:formic acid showed best performance with 17.0gL−1 glucose in CS hydrolysate.•CS ...hydrolysate pretreated by ChCl:formic acid was successfully applied in butanol fermentation.
In this study, an effective corn stover (CS) pretreatment method was developed for biobutanol fermentation. Deep eutectic solvents (DESs), consisted of quaternary ammonium salts and hydrogen donors, display similar properties to room temperature ionic liquid. Seven DESs with different hydrogen donors were facilely synthesized. Choline chloride:formic acid (ChCl:formic acid), an acidic DES, displayed excellent performance in the pretreatment of corn stover by removal of hemicellulose and lignin as confirmed by SEM, FTIR and XRD analysis. After optimization, glucose released from pretreated CS reached 17.0gL−1 and yield of 99%. The CS hydrolysate was successfully utilized in butanol fermentation by Clostridium saccharobutylicum DSM 13864, achieving butanol titer of 5.63gL−1 with a yield of 0.17gg−1 total sugar and productivity of 0.12gL−1h−1. This study demonstrates DES could be used as a promising and biocompatible pretreatment method for the conversion of lignocellulosic biomass into biofuel.
As the largest developing country, China has some of the worst air quality in the world. Heavy smog in January 2013 led to unprecedented public concern about the health impact of exposure to ...particulate matter. Conducting health impact assessments of particulate matter has thus become an urgent task for public health practitioners. Combined estimates of the health effects of exposure to particulate matter from quantitative reviews could provide vital information for epidemiology-based health impact assessments, but estimates for the Chinese population are limited.
On December 31, 2013, we systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases using as keywords names of 127 major cities in Mainland China, Hong Kong, and Taiwan. From among the 1464 articles identified, 59 studies were manually screened. Random-effects or fixed-effects models were used to combine their risk estimates, the funnel plots with Egger test were performed to evaluate the publication bias and Meta regression were run to explore the association between exposure to particulate matter with aerodynamic diameters less than 10 and 2.5µm (PM10 and PM2.5) and the resulting health effects by the Comprehensive Meta Analysis.
In terms of short-term effects, the combined excess risks of total non-accidental mortality, mortality due to cardiovascular disease, and mortality due to respiratory disease were 0.36% (95% confidence interval 95%CI: 0.26%, 0.46%), 0.36% (95%CI: 0.24%, 0.49%), and 0.42% (95%CI: 0.28%, 0.55%), for each 10μg/m3 increase in PM10. A 10μg/m3 increase in PM2.5 was associated with a 0.40% (95%CI: 0.22%, 0.59%) increase in total non-accidental mortality, a 0.63% (95%CI: 0.35%, 0.91%) increase in mortality due to cardiovascular disease, and a 0.75% (95%CI: 01.39%, 1.11%) increase in mortality due to respiratory disease. For constituent-specific mortality, increases of 0.40–3.11% were associated with an increase of 10ng/m3 for nickel in PM. The summary estimate ranges of hospital utilization were 0.08% ~0.72% and –0.58% ~1.32% for a 10μg/m3 increase in PM10 and PM2.5. In terms of long-term effects, a 10μg/m3 increase of PM10 corresponded to 23–67% increase in the risk of mortality.
Short exposures to PM10 and PM2.5 are associated with increases in mortality, but evidence of constituent-associated health effects, long-term effects and morbidity in China is still inadequate.
•Of 1464 indentified articles, 59 epidemiological studies reported from 1999 to 2013 were included in the meta-analysis, which involved 22 cities in mainland China, Hong Kong and Taiwan.•For a standardized increment in particulate matter with aerodynamic diameters less than 10 and 2.5µm (PM10 and PM2.5), excess risks of mortality and morbidity, as reflected in hospital utilization, were summarized.•Short exposures of aerodynamic diameters less than 10 and 2.5µm (PM10 and PM2.5) are positively associated with increases in mortality due to non-accidental cause, cardiovascular disease and respiratory disease.•Evidence of constituent-associated health effect, long-term effects and morbidity in China is still insufficient.
Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes
. Many aGPCRs are activated by a conserved internal (tethered) ...agonist sequence known as the Stachel sequence
. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G
: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-β-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W
and the constitution of a hydrogen-bond network formed by Q
/Y
and the P
/V
φφG
motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G
coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G
-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G
. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G
coupling.
Many animals exploit several niches sequentially during their life cycles, a fitness referred to as ontogenetic niche shift (ONS). To successfully accomplish ONS, transition between development ...stages is often coupled with changes in one or more primitive, instinctive behaviors. Yet, the underlining molecular mechanisms remain elusive. We show here that Leptinotarsa decemlineata larvae finish their ONS at the wandering stage by leaving the plant and pupating in soil. At middle wandering phase, larvae also switch their phototactic behavior, from photophilic at foraging period to photophobic. We find that enhancement of juvenile hormone (JH) signal delays the phototactic switch, and vise verse. Moreover, RNA interference (RNAi)-aided knockdown of LdPTTH (prothoracicotropic hormone gene) or LdTorso (PTTH receptor gene) impairs avoidance response to light, a phenotype nonrescuable by 20-hydroxyecdysone. Consequently, the RNAi beetles pupate at the soil surface or in shallow layer of soil, with most of them failing to construct pupation chambers. Furthermore, a combination of depletion of LdPTTH/LdTorso and disturbance of JH signal causes no additive effects on light avoidance response and pupation site selection. Finally, we establish that TrpA1 (transient receptor potential (TRP) cation channel) is necessary for light avoidance behavior, acting downstream of PTTH. We conclude that JH/PTTH cascade concomitantly regulates metamorphosis and the phototaxis switch, to drive ONS of the wandering beetles from plant into soil to start the immobile pupal stage.
Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial ...omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G
or G
trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.
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•A new solid acid catalyst based on coal fly ash solid acid was developed for furfural production.•SO42−/SnO2-Al2O3-CFA displayed high activity in NH4Cl-solution/toluene biphasic ...system.•The highest furfural yield of 84.7% and selectivity of 85.1% were achieved.•SO42−/SnO2-Al2O3-CFA and toluene could be recycled for five times.
A solid acid catalyst SO42−/SnO2-Al2O3-CFA was synthesized based on industrial waste coal fly ash (CFA) as carrier and applied in the conversion of oxalic acid pretreated corn stover hydrolysate to produce furfural. Physical properties of the solid acid catalyst were characterized by SEM, FTIR, XRD, BET, EDAX, and NH3-TPD. Highly wrinkled structure of SO42−/SnO2-Al2O3-CFA could provide more specific surface area for the covalent linkage between SiO2 and SnO2. Factors influencing the efficacy of SO42−/SnO2-Al2O3-CFA were systematically explored. The highest furfural yield of 84.7% was reached in NH4Cl-toluene biphasic system at 180 °C for 30 min. The recyclability of SO42−/SnO2-Al2O3-CFA and toluene could be achieved for five batches with stable performance in transformation of xylose-rich corn stover hydrolysate. This study provided a novel solid acid catalyst with promising potential in the synthesis of furfural from corn stover.
Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) turn out to be a promising source of cell‐free therapy. Here, we investigated the biodistribution and effect of nebulized human ...adipose‐derived MSC‐EVs (haMSC‐EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC‐EVs in healthy volunteers. DiR‐labelled haMSC‐EVs were used to explore the distribution of nebulized haMSC‐EVs in the murine model. Pseudomonas aeruginosa‐induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL‐6, TNF‐α and IL‐10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC‐EVs through the nebulized route. Twenty‐four healthy volunteers were involved and received the haMSC‐EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC‐EVs improved survival rate to 80% at 96 h in P. aeruginosa‐induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC‐EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC‐EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC‐EVs in lung injury diseases.
Pd/Cu-catalyzed cascade Heck-type reactions of alkenyl halides with terminal alkynes have been developed. This research provides an efficient atom-economical approach to access a variety of highly ...substituted pyrrolidines in moderate to good yields. This protocol features readily available substrates, broad substrate scope, easy scale-up, high selectivities and versatile transformations.
Pd/Cu-catalyzed cascade Heck-type reactions of alkenyl halides with terminal alkynes have been developed. This research provides an efficient atom-economical approach to access a variety of highly substituted pyrrolidines in moderate to good yields.
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