Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic ...synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N‐heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late‐stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.
Organocatalytic acylfluoroalkylation: A multicomponent radical acylfluoroalkylation of olefins through NHC organocatalysis was developed, and over 120 examples of fluoroketones were facilely accessed from simple materials. Moreover, a dearomative difunctionalization of indoles could be readily achieved in a highly diastereoselective manner. The generality and practicality were highlighted by the late‐stage modification of drug skeletons.
The anomalous Hall effect is a fundamental transport process in solids arising from the spin-orbit coupling. In a quantum anomalous Hall insulator, spontaneous magnetic moments and spin-orbit ...coupling combine to give rise to a topologically nontrivial electronic structure, leading to the quantized Hall effect without an external magnetic field. Based on first-principles calculations, we predict that the tetradymite semiconductors Bi₂Te₃, Bi₂Se₃, and Sb₂Te₃ form magnetically ordered insulators when doped with transition metal elements (Cr or Fe), in contrast to conventional dilute magnetic semiconductors where free carriers are necessary to mediate the magnetic coupling. In two-dimensional thin films, this magnetic order gives rise to a topological electronic structure characterized by a finite Chern number, with the Hall conductance quantized in units of e²/h (where e is the charge of an electron and h is Planck's constant).
Elevated levels of neutrophils have been associated with poor survival in various cancers, but direct evidence supporting a role for neutrophils in the immunopathogenesis of human cancers is lacking.
...A total of 573 patients with gastric cancer were enrolled in this study. Immunohistochemistry and real-time PCR were performed to analyze the distribution and clinical relevance of neutrophils in different microanatomic regions. The regulation and function of neutrophils were assessed both
and
Increased neutrophil counts in the peripheral blood were associated with poor prognosis in gastric cancer patients. In gastric cancer tissues, neutrophils were enriched predominantly in the invasive margin, and neutrophil levels were a powerful predictor of poor survival in patients with gastric cancer. IL17
neutrophils constitute a large portion of IL17-producing cells in human gastric cancer. Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. Moreover, neutrophils at the invasive margin were a major source of matrix metalloproteinase-9, a secreted protein that stimulates proangiogenic activity in gastric cancer cells. Accordingly, high levels of infiltrated neutrophils at the invasive margin were positively correlated with angiogenesis progression in patients with gastric cancer.
These data provide direct evidence supporting the pivotal role of neutrophils in gastric cancer progression and reveal a novel immune escape mechanism involving fine-tuned collaborative action between cancer cells and immune cells in the distinct tumor microenvironment.
.
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β‐fluoroalkyl‐containing cinnamate derivatives. The ...reaction proceeds through visible‐light‐promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio‐ and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
Leading light: A regio‐ and stereoselective fluoroarylation of allenic esters through visible‐light‐promoted gold redox catalysis with cost‐effective Et3N⋅3 HF as the nucleophilic fluorine source is reported. Preliminary mechanistic studies reveal concomitant activation of the allene motif by a high‐valent gold complex and the hydrogen fluoride by hydrogen bonding with the ester group, thereby enabling the otherwise challenging fluorine incorporation.
Abstract
Rationally constructing and manipulating the in situ formed catalytically active surface of catalysts remains a tremendous challenge for a highly efficient water electrolysis. Herein, an ...anion and cation co‐induced strategy is presented to modulate in situ catalyst dissolution‐redeposition and to achieve the directional reconstruction of Zn and S co‐doped Fe
2
O
3
and Fe
3
O
4
on iron foams (Zn,S‐Fe
2
O
3
‐Fe
3
O
4
/IF), for oxygen evolution reaction (OER). Benefiting from Zn, S co‐doping and the presence of Fe
3
O
4
, a directionally reconstructed surface is obtained. The Fe
2
O
3
in the Zn,S‐Fe
2
O
3
‐Fe
3
O
4
/IF is directionally reconstructed into FeOOH (Zn,S‐Fe
3
O
4
‐FeOOH/IF), in which the S leaching promotes the Fe dissolution and the Zn co‐deposition regulates the activity of the obtained FeOOH. Moreover, the presence of Fe
3
O
4
provides a stable site for FeOOH deposition, and thus causes more FeOOH active components to be formed. Directionally reconstructed Zn,S‐Fe
3
O
4
‐FeOOH/IF outperformes many state‐of‐the‐art OER catalysts and demonstrates a remarkable stability. The experimental and density functional theory (DFT) calculation results show that the introduction of Zn‐doped FeOOH with abundant oxygen vacancies through directional reconstruction has activated lattice O atoms, facilitating the OER process on the heterojunction surface following the lattice oxygen mechanism (LOM) pathway. This work makes a stride in co‐induced strategy modulating directional reconstruction.
The brown planthopper, Nilaparvata lugens, the most destructive pest of rice, is a typical monophagous herbivore that feeds exclusively on rice sap, which migrates over long distances. Outbreaks of ...it have re-occurred approximately every three years in Asia. It has also been used as a model system for ecological studies and for developing effective pest management. To better understand how a monophagous sap-sucking arthropod herbivore has adapted to its exclusive host selection and to provide insights to improve pest control, we analyzed the genomes of the brown planthopper and its two endosymbionts.
We describe the 1.14 gigabase planthopper draft genome and the genomes of two microbial endosymbionts that permit the planthopper to forage exclusively on rice fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have detectable shared homology with the proteomes of the other 14 arthropods included in this study, reflecting large-scale gene losses including in evolutionarily conserved gene families and biochemical pathways. These unique genomic features are functionally associated with the animal's exclusive plant host selection. Genes missing from the insect in conserved biochemical pathways that are essential for its survival on the nutritionally imbalanced sap diet are present in the genomes of its microbial endosymbionts, which have evolved to complement the mutualistic nutritional needs of the host.
Our study reveals a series of complex adaptations of the brown planthopper involving a variety of biological processes, that result in its highly destructive impact on the exclusive host rice. All these findings highlight potential directions for effective pest control of the planthopper.
The formation of aryl‐alkyl ether bonds through cross coupling of alcohols with aryl halides represents a useful strategic departure from classical SN2 methods. Numerous tactics relying on Pd‐, Cu‐, ...and Ni‐based catalytic systems have emerged over the past several years. Herein we disclose a Ni‐catalyzed electrochemically driven protocol to achieve this useful transformation with a broad substrate scope in an operationally simple way. This electrochemical method does not require strong base, exogenous expensive transition metal catalysts (e.g., Ir, Ru), and can easily be scaled up in either a batch or flow setting. Interestingly, e‐etherification exhibits an enhanced substrate scope over the mechanistically related photochemical variant as it tolerates tertiary amine functional groups in the alcohol nucleophile.
Highly chemoselective O‐arylation was achieved by electrochemically‐driven nickel catalysis. This method exhibits broad substrate scope comparable to state‐of‐the‐art Pd, Cu and photochemically facilitated Ni catalysis. This e‐etherification forged ether bonds in demanding settings where other methods failed. With its excellent scalability, this work represents a modular, mild, and simple ether bond formation for contemporary medicinal chemistry.
Spatiotemporal control of singlet oxygen (1O2) release is a major challenge for photodynamic therapy (PDT) against cancer with high therapeutic efficacy and minimum side effects. Here a ...selenium-rubyrin (NMe2Se4N2)-loaded nanoparticle functionalized with folate (FA) was designed and synthesized as an acidic pH-activatable targeted photosensitizer. The nanoparticles could specifically recognize cancer cells via the FA-FA receptor binding and were selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which NMe2Se4N2 was activated to produce 1O2. The pH-controllable release of 1O2 specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the 1O2 generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at meso-position led to the pH-controllable activation of NMe2Se4N2. Under near-infrared (NIR) irradiation, NMe2Se4N2 possessed high singlet oxygen quantum yield (ΦΔ) at an acidic pH (ΦΔ = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological pH (ΦΔ = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH-activatable photosensitization at NIR region and the cancer cell-targeting feature led to excellent capability to selectively kill cancer cells and prevent the damage to normal cells, which greatly lowered the side effects. Through intravenous injection of FA-NMe2Se4N2 nanoparticles in tumor-bearing mice, tumor elimination was observed after NIR irradiation. This work presents a new paradigm for specific PDT against cancer and provides a new avenue for preparation of highly efficient photosensitizers.
The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet ...understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97‐H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor‐beta 1 (TGFβ1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co‐culture of MHCC97‐H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC‐treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm3vs 2223.75 ± 1000.60 mm3, P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFβ1 and MMP‐2 was significantly downregulated in the MSC‐treated HCC cells. TGFβ siRNA concurrently downregulated expression of TGFβ and MMP‐2 in HCC cells and blocked the MSC‐induced proliferation and invasiveness of MHCC97‐H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFβ1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546–2553)
The electronic regulation and surface reconstruction of earth‐abundant electrocatalysts are essential to efficient oxygen evolution reaction (OER). Here, an inverse‐spinel Co,S atomic pair codoped ...Fe3O4 grown on iron foam (Co,S‐Fe3O4/IF) is fabricated as a cost‐effective electrocatalyst for OER. This strategy of Co and S atomic pair directional codoping features accelerates surface reconstruction and dynamically stabilizes electronic regulation. CoS atomic pairs doped in the Fe3O4 crystal favor controllable surface reconstruction via sulfur leaching, forming oxygen vacancies and Co doping on the surface of reconstructed FeOOH (Co‐FeOOH‐Ov/IF). Before and after surface reconstruction via in situ electrochemical process, the Fe sites with octahedral field dynamically maintains an appropriate electronic structure for OER intermediates, thus exhibiting consistently excellent OER performance. The electrochemically tuned Fe‐based electrodes exhibit a low overpotential of 349 mV at a current density of 1000 mA cm−2, a slight Tafel slope of 43.3 mV dec−1, and exceptional long‐term electrolysis stability of 200 h in an alkaline medium. Density functional theory calculations illustrate the electronic regulation of Fe sites, changes in Gibbs free energies, and the breaking of the restrictive scaling relation between OER intermediates. This work provides a promising directional codoping strategy for developing precatalysts for large‐scale water‐splitting systems.
CoS atomic pair directional co‐doped Fe3O4 as an oxygen evolution reaction precatalyst that display a facile in situ electrochemical reconstruction process to finally achieve a Co‐doped FeOOH with oxygen vacancies is designed. CoS atomic pairs doped in the Fe3O4 crystal favour controllable surface reconstruction via sulphur leaching, forming oxygen vacancies and Co doping on the surface of reconstructed FeOOH.
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