Chain walking has been an efficient route to realize the functionalization of inert C(sp3)−H bonds, but this strategy is limited to mono‐olefin migration and functionalization. Herein, we demonstrate ...the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp3)−H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes.
The enantioselective migratory allylation of remote dienes via palladium‐catalyzed simultaneous/directed chain walking is reported. The transformation provides a potential route to achieving stereoselective functionalization of multiple continuous C(sp3)−H bonds.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and β subunits
. A tethered agonism mediated by ...the 'Stachel sequence' of the β subunit has been proposed to have central roles in aGPCR activation
. Here we present three cryo-electron microscopy structures of aGPCRs coupled to the G
heterotrimer. Two of these aGPCRs are activated by tethered Stachel sequences-the ADGRG2-β-G
complex and the ADGRG4-β-G
complex (in which β indicates the β subunit of the aGPCR)-and the other is the full-length ADGRG2 in complex with the exogenous ADGRG2 Stachel-sequence-derived peptide agonist IP15 (ADGRG2(FL)-IP15-G
). The Stachel sequences of both ADGRG2-β and ADGRG4-β assume a U shape and insert deeply into the seven-transmembrane bundles. Constituting the FXφφφXφ motif (in which φ represents a hydrophobic residue), five residues of ADGRG2-β or ADGRG4-β extend like fingers to mediate binding to the seven-transmembrane domain and activation of the receptor. The structure of the ADGRG2(FL)-IP15-G
complex reveals the structural basis for the improved binding affinity of IP15 compared with VPM-p15 and indicates that rational design of peptidic agonists could be achieved by exploiting aGPCR-β structures. By converting the 'finger residues' to acidic residues, we develop a method to generate peptidic antagonists towards several aGPCRs. Collectively, our study provides structural and biochemical insights into the tethered activation mechanism of aGPCRs.
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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
Optical fiber distributed acoustic sensing (DAS) based on phase sensitive optical time domain reflectometry (ϕ-OTDR) has a great demand in many application fields with large signals, such as railway ...safety monitoring, cable vibration detection, etc. However, due to the inherent limits of phase unwrapping algorithm, the large signal whose phase change exceeds π cannot be recovered correctly by DAS. In this work, the differential-unwrapping-integral (DUI) algorithm is proposed and demonstrated to replace the traditional unwrapping algorithm for large signal recovery. By utilizing differential operation to compress the signal amplitude, the large phase signal can be converted into small signal which can be recovered through unwrapping. Then, multiple integral operations and polynomial fitting compensation algorithm are applied onto the differential signal to recover the original phase signal without any signal-to-noise ratio(SNR) sacrificed. In theory, the maximum measurable phase of DUI can be improved 1390 times compared with traditional DUI algorithm. Further, the experimental results demonstrate that the dynamic range of DAS with DUI can reach up to 131.7 dB. Moreover, DUI algorithm has been tested and verified in the field test for recording the digging signals with large amplitude. This scheme can be applicable for all phase-demodulation-based sensing techniques without increasing the system complexity.
Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes ...influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP‐1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium‐based and Transwell‐based coculture systems. Furthermore, the potential pathways and cyto‐/chemokines involved in Mφ‐mediated cementoblastic differentiation were screened and identified. In both systems, M2 subsets increased cementoblastic differentiation‐related gene/protein expression levels in cocultured PDLSCs, induced more PDLSCs to differentiate into polygonal and square cells, and enhanced alkaline phosphatase activity in PDLSCs. Furthermore, Akt and c‐Jun N‐terminal Kinase (JNK) signaling was identified as a potential pathway involved in M2 Mφ‐enhanced PDLSC cementoblastic differentiation, and cyto‐/chemokines (interleukin (IL)‐10 and vascular endothelial growth factor VEGF) secreted by M2 Mφs were found to be key players that promoted cell cementoblastic differentiation by activating Akt signaling. Our data indicate for the first time that Mφs are key modulators during PDLSC cementoblastic differentiation and are hence very important for the regeneration of multiple periodontal tissues, including the cementum. Although the Akt and JNK pathways are involved in M2 Mφ‐enhanced cementoblastic differentiation, only the Akt pathway can be activated via a cyto‐/chemokine‐associated mechanism, suggesting that players other than cyto‐/chemokines also participate in the M2‐mediated cementoblastic differentiation of PDLSCs. Stem Cells 2019;37:1567–1580
Both the Akt and JNK axes are involved in the M2 macrophage‐enhanced cementoblastic differentiation of periodontal ligament stem cells, but only the Akt pathway can be activated via a cyto‐/chemokine‐associated mechanism.
CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its ...utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting “core-shell” artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.
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IJS, KILJ, NUK, PNG, UL, UM
Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing a remote leaving group is scarcely viewed as a potential allylation substrate. Herein, we ...describe feasible protocols to achieve regiodivergent allylic C−H functionalizations via palladium‐catalyzed remote substitution, which provides a novel strategy for the seldomly studied migratory Tsuji–Trost reaction. Dictated by a suitable ligand, a process that involved 4,3‐hydrofunctionalization of the generated conjugated diene intermediate via metal walking is observed in generally >20 : 1 regioselectivity. Unexpectedly, a related 1,4‐hydrofunctionalization pathway is found to be a major route with a newly synthesized electron‐rich bisphosphine ligand, which challenges the conventional viewpoint on the potential regioselectivity of hydrofunctionalizations of linear internal conjugated dienes via η3‐substitution. A series of deuterium experiments and kinetic studies provide a preliminary insight into the potential catalytic cycle.
Palladium‐catalyzed regiodivergent allylic C−H functionalizations were established via remote substitution, which provides a novel model for the seldomly studied migratory Tsuji–Trost reaction. 1,4‐Hydrofunctionalization of a conjugated diene intermediate was demonstrated to be feasible via a newly synthesized bisphosphine ligand.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Earth's climate is largely determined by its energy budget. Since the 1960s, satellite remote sensing has been used in estimating these energy budget components at both the top of the atmosphere ...(TOA) and the surface. Besides the broadband sensors that have been traditionally used for monitoring Earth's Energy Budget (EEB), data from a variety of narrowband sensors aboard both polar-orbiting and geostationary satellites have also been extensively employed to estimate the EEB components. This paper provides a comprehensive review of the satellite missions, state-of-the art estimation algorithms and the satellite products, and also synthesizes current understanding of the EEB and spatio-temporal variations. The TOA components include total solar irradiance, reflected shortwave radiation/planetary albedo, outgoing longwave radiation, and energy imbalance. The surface components include incident solar radiation, shortwave albedo, shortwave net radiation, longwave downward and upwelling radiation, land and sea surface temperature, surface emissivity, all-wave net radiation, and sensible and latent heat fluxes. Some challenges, and outlook such as virtual constellation of different satellite sensors, temporal homogeneity tests of long time-series products, algorithms ensemble, and products intercomparison are also discussed.
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BFBNIB, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In tandem: The title reaction of cyclohexadienone‐containing meso‐1,6‐dienynes with arylboronic acids through a tandem arylrhodation/conjugate addition sequence has been realized, and provides a ...novel approach to the enantioenriched cis‐hydrobenzofurans with both excellent yields and enantioselectivities. binap=2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl, Boc=tert‐butoxycarbonyl.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Microporous organic nanotubes (MONs) hold considerable promise for designing molecular-sieving membranes because of their high microporosity, customizable chemical functionalities, and favorable ...polymer affinity. Herein, we report the use of MONs derived from covalent organic frameworks to engineer 15-nm-thick microporous membranes via interfacial polymerization (IP). The incorporation of a highly porous and interpenetrated MON layer on the membrane before the IP reaction leads to the formation of polyamide membranes with Turing structure, enhanced microporosity, and reduced thickness. The MON-modified membranes achieve a remarkable water permeability of 41.7 L m
h
bar
and high retention of boron (78.0%) and phosphorus (96.8%) at alkaline conditions (pH 10), surpassing those of reported nanofiltration membranes. Molecular simulations reveal that introducing the MONs not only reduces the amine molecule diffusion toward the organic phase boundary but also increases membrane porosity and the density of water molecules around the membrane pores. This MON-regulated IP strategy provides guidelines for creating high-permeability membranes for precise nanofiltration.
In the face of huge amounts of image data, how to let the computer simulate human cognition of images and automatically classify images into different semantic categories have become a key issue in ...image semantic analysis. Image classification is based on some attribute of the image, and it is divided into pre-set categories. For human beings, image classification is not difficult but there is a series of problems in using computers to classify images: (1) images contain a large amount of information, which is complex, diverse, and indescribable; and (2) there is a huge difference between the physical expression of images and the conceptual information known by human beings. The traditional sparse coding method loses the spatial information when classifying images. In this paper, spatial pyramid multi-partition method is used to add spatial information restriction to the feature. The proposed multi-scale spatial latent semantic analysis method based on sparse coding has higher average classification accuracy than many existing methods, which verifies its effectiveness and robustness. Experiments also show that the classification accuracy of this paper is 2.1% higher than that of sparse coding for image classification (ScSPM) and the classification performance is 3.1% higher than that of ScSPM when the number of training images is 40. Compared with other methods, the classification performance of the proposed method is improved significantly.
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