Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor ...(GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and
H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.
Environmental inspection is to use GIS technology to design an environmental inspection network. The information collected through environmental testing can be saved and displayed in time through ...GIS, and the selected evaluation field can be monitored and analyzed in detail. This is the basis of scientific environmental management and environmental law enforcement supervision, and the basic work of environmental protection. The central goal of environmental monitoring is to provide data on the status quo and trend of environmental quality, judge environmental quality, assess current major environmental issues, and contribute to environmental management. Based on the analysis and classification of related literature, this paper adopts the method of literature induction to analyze the development trend of current research on the improvement and upgrade of network theory by domestic and foreign scholars. On this basis, the research on the network theory of improvement and upgrade is divided into three parts: the research on the dynamic factors of the upgrade, the research on the upgrade mechanism, and the research on the upgrade path. In China, the sources of PM2.5 are very complex, most of which come from the linear contribution of primary particulate matter. Therefore, the improvement of the response surface model and the establishment of real-time environmental detection and analysis tools suitable for PM2.5 emission characteristics and environmental concentration have high application value. The source of PM2.5 in indoor air environment can be divided into two parts. One is the emission of PM2.5 pollution sources in indoor buildings, and the other is the spread of PM2.5 pollutants from outdoor air to the indoor environment. In order to deal with air pollutants, we adopt pollutant emission control technology and control pollutant emission policies to achieve air pollution control.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Electronically matched nucleophilic 1,6‐conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5‐conjugate addition represents an electronically ...forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5‐conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5‐conjugate reaction, followed by inter‐ or intramolecular 3+2 cyclization. A migratory 1,5‐addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5‐addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis.
An unconventional umpolung protocol was demonstrated for novel 1,5‐conjugate additions via palladium hydride catalyst. Three catalytic reaction modes including 1,5‐addition cascade with inter‐ and intramolecular 3+2 cyclization and migratory 1,5‐addition were established via palladium or palladium/organo‐cocatalysis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The journal-thrust coupled bearing in diesel engine operates under complex load and high working temperature. Under extreme working conditions, it supports the crankshaft and prevents its axial ...movement through the lubrication of journal and thrust parts. This study is mainly aimed to establish the thermal elastohydrodynamic (TEHD) lubrication analysis model for textured journal-thrust coupled bearing, which considered the thermal and pressure coupled effects in the lubrication process by proposing the flow, pressure and thermal continuity conditions between the journal and thrust parts. A specific coupled bearing testing equipment was set up and the experimental results validated the correctness of the TEHD lubrication model. Necessity of considering thermal and pressure coupled effect was confirmed through comparison of different models. Apart from that, parametric analyses were conducted to explore the influences of thermal and pressure coupled effects on lubrication performances and dynamic characteristics under different eccentricity ratio of journal part, geometry film thickness of thrust part and surface topography (mainly realized by texture distribution of thrust part).
•The journal-thrust coupled bearing in diesel engine is found necessary to consider the flow, pressure and thermal continuity conditions of the common boundary.•After considering the coupled effect mentioned above, the bearing capacity, maximum temperature, stiffness and damping of journal and thrust parts are improved.•With the reduction of geometry oil film thickness, the coupled effect has more significant influence on lubrication performances and dynamic characteristics, and the trend of each part is different. Similarly, the coupled effect also has a similar influence with the change of texture distribution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ribbon‐shaped single crystal transistors based on naphthalene diimide Cl2‐NDI exhibit excellent n‐channel performance with the mobility as high as 8.6 cm2V−1s−1 in air. The combination of ambient ...stability and high mobility n‐channel transport closes the gap between p‐ and n‐channel SCFETs and opens the door for the manufacture of high performance complementary organic circuits.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This article reviews the molecular structure, expression pattern, physiological function, pathological roles and mo- lecular mechanisms of Twistl in development, genetic disease and cancer. Twistl is ...a basic helix-loop-helix domain- containing transcription factor. It forms homo- or hetero-dimers in order to bind the Ndel E-box element and acti- vate or repress its target genes. During development, Twistl is essential for mesoderm specification and differentia- tion. Heterozygous loss-of-function mutations of the human Twistl gene cause several diseases including the Saethre- Chotzen syndrome. The Twistl-null mouse embryos die with unclosed cranial neural tubes and defective head mesen- chyme, somites and limb buds. Twistl is expressed in breast, liver, prostate, gastric and other types of cancers, and its expression is usually associated with invasive and metastatic cancer phenotypes. In cancer cells, Twistl is upregulated by multiple factors including SRC-1, STAT3, MSX2, HIF-la, integrin-linked kinase and NF-κB. Twistl significantly enhances epithelial-mesenchymal transition (EMT) and cancer cell migration and invasion, hence promoting cancer metastasis. Twistl promotes EMT in part by directly repressing E-cadherin expression by recruiting the nucleosome remodeling and deacetylase complex for gene repression and by upregulating Bmil, AKT2, YB-1, etc. Emerging evi- dence also suggests that Twistl plays a role in expansion and chemotherapeutic resistance of cancer stem cells. Fur- ther understanding of the mechanisms by which Twistl promotes metastasis and identification of Twistl functional modulators may hold promise for developing new strategies to inhibit EMT and cancer metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Transition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective ...allylic C(sp
3
)-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp
3
)-H functionalization. Through palladium hydride-catalyzed chain-walking and allylic substitution, allylic C-H functionalization of a wide range of acyclic nonconjugated dienes is achieved in high yields (up to 93% yield), high enantioselectivities (up to 98:2 er), and with 100% atom efficiency. Exploring the reactivity of substrates with varying p
K
a
values uncovers a reasonable scope of nucleophiles and potential factors controlling the reaction. A set of efficient downstream transformations to enantiopure skeletons showcase the practical value of the methodology. Mechanistic experiments corroborate the PdH-catalyzed asymmetric migratory allylic substitution process.
The development of interfacial polymerization (IP) technique has revolutionarily changed our methods for water treatment and desalination. Over decades, researchers have devoted their efforts to ...further improve this marvelous technology through versatile approaches such as optimizing chemical compositions, improving membrane structures and reducing the thickness of selective layers. Recently, constructing interlayers on a support membrane is proven to be a powerful tool to mediate the IP kinetics, which facilitates the formation of thinner polyamide (PA) layers with desired nanostructures. Decreased permeation resistance based on thinner PA layer and enhanced permeable area derived from nanostructures synergistically bring the membrane permeability to an unprecedented height. In this review, we will comprehensively analyze these up-to-date works to discuss the functions of different interlayers from material composition, fabrication methods and designed applications. An empirical relationship between interlayer building materials (chemical composition and dimensionality on a nanoscale) and initial membrane performances (permeability and selectivity) will be established to give inspirations to future works.
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•Recent advances in interlayer enhanced TFC membranes have been summarized.•The relationship between the initial membranes permeability and selectivity and the interlayer materials has been established.•The influence of the nanoscale dimensionality of interlayer materials on the interfacial polymerization reaction has been discussed.•An outlook and challenge for fabricating interlayer enhanced reverse osmosis membranes and hollow fiber membranes have been proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The enantioselective construction of carbon-heteroatom and carbon-carbon bonds that are alpha to ketones leads to the formation of substructures that are ubiquitous in natural products, ...pharmaceuticals and agrochemicals. Traditional methods to form such bonds have relied on combining ketone enolates with electrophiles. Reactions with heteroatom-based electrophiles require special reagents in which the heteroatom, which is typically nucleophilic, has been rendered electrophilic by changes to the oxidation state. The resulting products usually require post-synthetic transformations to unveil the functional group in the final desired products. Moreover, different catalytic systems are typically required for the reaction of different electrophiles. Here, we report a strategy for the formal enantioselective α-functionalization of ketones to form products containing a diverse array of substituents at the alpha position with a single catalyst. This strategy involves an unusual reversal of the role of the nucleophile and electrophile to form C-N, C-O, C-S and C-C bonds from a series of masked ketone electrophiles and a wide range of conventional heteroatom and carbon nucleophiles catalysed by a metallacyclic iridium catalyst.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ