Synthesis of Indolyl Phenyl Diketones through Visible-Light-Promoted Ni-Catalyzed Intramolecular Cyclization/Oxidation Sequence of Ynones.

The combination of visible light catalysis and Ni catalysis has enabled the synthesis of indolyl phenyl diketones through the cyclization/oxidation process of ynones. This reaction proceeded under mild and base-free conditions and showed a broad scope and feasibility for gram-scale synthesis. Several natural products and biologically interesting molecules could be readily postfunctionalized by this method.

Straightforward Access to Free ß2,3,3-Amino Acids through One Pot C-H Activation/C-C Cleavage.

The first synthesis of unnatural ß2,3,3-amino acids with a spirocyclic backbone by one-pot protocol has been presented. This reaction features wide functional group tolerance and feasibility of post-functionalization of natural products and biologically important molecules. Novel dipeptide and tripeptide structures were assembled using this newly developed ß2,3,3-amino acid in high efficiency. The combination of C-H activation and C-C cleavage for the synthesis of ß-amino acids would trigger more promising synthetic routes for this compound.

Synthesis of Aryl-methylene Ethers through Pd(0)-Catalyzed Coupling between Hydrobenzoxazoles and Dichloromethane.

Using dichloromethane (DCM) as the C1 feedstock, the first Pd(0)-catalyzed synthesis of aryl-methylene ether motifs from hydrobenzoxazoles (hydrothiazoles) has been reported. This protocol has exhibited an ample substrate scope (38 examples) and wide functional group tolerance. Aryl-methylene ether adducts have been successfully engaged in coupling with isocyanate to provide bis-iminoisoindolinones. In this reaction, DCM has served as a twofold electrophile for reaction with hydrobenzoxazoles via double C-Cl bond cleavage.

Directed Palladium Catalyzed C-H (Ethoxycarbonyl)difluoromethylthiolation Reactions.

The unprecedented Pd-catalyzed (ethoxycarbonyl)difluoromethylthiolation reaction of various unsaturated derivatives was studied. In the presence of the (ethoxycarbonyl)difluoromethylsulfenamide reagent I and under mild reaction conditions (60 °C), both 2-(hetero)aryl and 2-(α-aryl-vinyl)pyridine derivatives were smoothly functionalized with this methodology (37 examples, up to 87 % yield). Moreover, the synthetic interest of this fluorinated moiety was further showcased by its conversion into various original fluorinated residues. Finally, a plausible mechanism for this transformation was suggested.

Identification of shared neoantigens in esophageal carcinoma by the combination of comprehensive analysis of genomic data and in silico neoantigen prediction.

Neoantigens are attractive targets for cancer immunotherapy. The identification of neoantigens shared by different patients could promote the broad application of neoantigen-based immunotherapy. This study aimed to investigate shared neoantigens in esophageal carcinoma. By combining a comprehensive analysis of mutation data of 722 patients with esophageal carcinoma (EC) and in silico neoantigen prediction, we obtained 216 recurrent neoantigen candidates predicted to bind to high-frequency class I human leukocyte antigen (HLA) alleles. We further performed immunogenicity validation tests on five high-frequency HLA-A*0201 binding neoantigens derived from TP53 mutations. The results demonstrated that the peptides p53 H193R193_203, R248Q245_254, and R273H264_274 could efficiently prime peptide-specific CD8+ T cells to secrete IFN-γ and lyse mutant peptide-pulsed T2 cells. In conclusion, we obtained a group of shared neoantigen candidates in esophageal carcinoma and validated the immunogenicity of three novel TP53 neoantigens. These peptides might be potential targets for immunotherapy.

Constructing N-doping biomass-derived carbon with hierarchically porous architecture to boost fast reaction kinetics for higfh-performance lithium storage.

Active biomass-derived carbons are brought into focus on boosting high-performance lithium storage. However, their low electric conductivity and poor ion diffusion kinetics during the lithium storage reactions remain confusing topics. This study demonstrates a novel and effective strategy of dual system activation process to construct the nitrogen-doped biomass-derived carbon with hierarchically porous architecture (HNBC), which is composed of the three-dimensional porous networks connected by carbon nanorods and the flake-like edges constructed by carbon nanosheets. A large amount of nitrogen doping can improve the conductivity and facilitate the charge transfer during charging/discharging, while the hierarchically porous structure can decrease the diffusion path for lithium-ion transport, enabling fast diffusion and charge-transfer dynamics. The HNBC electrode displays a high lithium-ion storage capacity of above 1392 mAh g-1 at 0.1 A g-1 and superior stability. Moreover, the assembled asymmetric lithium-ion capacitor exhibits excellent cycling stability and delivers a high power density of 225 W kg-1 with an energy density of 186.31 W h kg-1. This dual system activation strategy may inspire the reasonable design of new-generation progressive carbon-based electrodes for high-performance lithium storage devices.

Delivering 2-Aryl Benzoxazoles through Metal-Free and Redox-Neutral De-CF3 Process.

An unexpected cleavage of the Csp3-CF3 bond of CF3-hydrobenzoxazoles has been disclosed, affording a range of 2-aryl benzoxazoles under metal-free and redox-neutral conditions. This transformation has demonstrated broad substrate scope and good compatibility of functional groups. 2-Aryl benzothiazole and 2-aryl benzoimidazole could be smoothly assembled in the same manner. On the basis of preliminary mechanistic studies, base initiated and aromatization driven ß-carbon elimination was considered to be the key step for the formation of 2. This reaction offers an alternative, facile, and sustainable route to access important 2-aryl benzoxazole motifs.

Merging Imidazolidines with a Trifluoromethylated Tetrasubstituted Carbon through Tungsten Catalyzed 1,3-Dipolar Cycloaddition.

An unprecedented 1,3-dipole cycloaddition between acyclic CF3-ketimines and N-benzyl azomethine ylide has been allowed by tungsten catalysis, furnishing a range of novel imidazolidines bearing a trifluoromethylated tetrasubstituted carbon center. This reaction appears as one of rare examples that challenging acyclic CF3-ketimines have been engaged in 1,3-cycloaddition reactions. The capability for gram-scale synthesis and variant derivatizations of cycloaddition adducts illustrates the synthetic potential of this approach. This protocol provides a facile access to a rapidly enlarging pool of motifs with a trifluoromethylated fully substituted carbon.

The [3+2] Annulation of CF3-Ketimines by Re Catalysis: Access to CF3-Containing Amino Heterocycles and Polyamides.

Transition metal catalyzed [3 + 2] annulation of imines with double bonds via directed C-H activation offers a direct access to amino cyclic motifs. However, owing to weak coordination and steric hindrance, trifluoromethylated ketimines have been an unaddressed challenge for TM-catalyzed annulations. Here, a rhenium-catalyzed [3 + 2] annulation of trifluoromethylated ketimines with isocyanates via C(sp2)-H activation has been disclosed. This approach provides an efficient platform for rapid access to a privileged library of CF3-containing iminoisoindolinones and polyamides by utilizing challenging CF3-ketimines as the annulation component. The capability of gram scale synthesis, the post-functionalization of the cyclization adduct, the derivation of complex natural molecules and the facile synthesis of polyamides highlight a diversity of synthetic potential of the current methodology.

Synthesis of ß-CF3 ß-Amino Esters with an Indane Backbone by Rhenium-Catalyzed [3+2] Annulation.

The [3+2] annulation of trifluoromethylated ketimines with acrylates has been enabled by rhenium-catalyzed C-H activation, delivering a variety of ß-CF3 ß-amino esters. The reaction has exhibited broad substrate generality regarding aromatic CF3-ketimines and acrylates, the ability for gram scale synthesis, and facile derivation of the annulation products. The transformation is one of the few examples in which challenging sp2 C-H bonds of CF3-ketimines have been functionalized. The rapid assembly of biologically important fluorinated ß-amino esters by this strategy will benefit the related studies and inspire a new approach for fluorinated motif synthesis.

ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress.

RNA editing of adenosine to inosine (A to I) is catalyzed by ADAR1 and dramatically alters the cellular transcriptome, although its functional roles in somatic cell reprogramming are largely unexplored. Here, we show that loss of ADAR1-mediated A-to-I editing disrupts mesenchymal-to-epithelial transition (MET) during induced pluripotent stem cell (iPSC) reprogramming and impedes acquisition of induced pluripotency. Using chemical and genetic approaches, we show that absence of ADAR1-dependent RNA editing induces aberrant innate immune responses through the double-stranded RNA (dsRNA) sensor MDA5, unleashing endoplasmic reticulum (ER) stress and hindering epithelial fate acquisition. We found that A-to-I editing impedes MDA5 sensing and sequestration of dsRNAs encoding membrane proteins, which promote ER homeostasis by activating the PERK-dependent unfolded protein response pathway to consequently facilitate MET. This study therefore establishes a critical role for ADAR1 and its A-to-I editing activity during cell fate transitions and delineates a key regulatory layer underlying MET to control efficient reprogramming.

Copper-Mediated Deacylative Coupling of Ynones via C-C Bond Activation under Mild Conditions.

The intermolecular deacylative coupling of unstrained ynones via C-C bond activation was accomplished by a CuCl-bpy system under mild reaction conditions. This protocol features facile cleavage of the C-C bond at room temperature, broad substrate scope, and efficient construction of important symmetric and unsymmetrical 1,3-diyne adducts through homo or cross coupling of ynones, respectively. The preliminary mechanistic investigations indicated that an acyl copper(III) complex is likely involved in this process.

BiCl3-Mediated direct functionalization of unsaturated C-C bonds with an electrophilic SCF2PO(OEt)2 reagent.

A transition metal-free approach was developed for the direct difunctionalization of disubstituted alkynes and terminal alkenes with concomitant formation of C-SCF2PO(OEt)2 and C-Cl bonds. The BiCl3-mediated reaction offered access to high value-added functionalized scaffolds in a single operation under mild conditions. Extension to SCF2PO(OEt)2-containing alkynes was also studied.

Optical sensitivity enhancement in grating based micromechanical accelerometer by reducing non-parallelism error.

We report on optical sensitivity enhancement in a grating-based micromechanical accelerometer, which was achieved by reducing the non-parallelism error between the grating and reflected mirror. Based on the multi-slit Fraunhofer diffraction theory, an equivalent optical model is proposed in order to discuss the non-parallelism induced error that is caused by the residual stress in material and fabrication. An integrated fabrication flow with optimized quartz based and silicon based procedure is then presented to improve the parallelism between the grating and mirror, and to realize a hermetic package using silicon islands for the electrical interconnection. We experimentally characterize accelerometers' behavior by an interferometric beam detecting setup, which reveals the acceleration measurement with a scale factor improvement, noise floor decrease, and thus a bias stability enhancement from 2 mg to 0.35 mg (20 seconds interval, 1 g = 9.8 m/s2).

RED-ML: a novel, effective RNA editing detection method based on machine learning.

With the advancement of second generation sequencing techniques, our ability to detect and quantify RNA editing on a global scale has been vastly improved. As a result, RNA editing is now being studied under a growing number of biological conditions so that its biochemical mechanisms and functional roles can be further understood. However, a major barrier that prevents RNA editing from being a routine RNA-seq analysis, similar to gene expression and splicing analysis, for example, is the lack of user-friendly and effective computational tools. Based on years of experience of analyzing RNA editing using diverse RNA-seq datasets, we have developed a software tool, RED-ML: RNA Editing Detection based on Machine learning (pronounced as "red ML"). The input to RED-ML can be as simple as a single BAM file, while it can also take advantage of matched genomic variant information when available. The output not only contains detected RNA editing sites, but also a confidence score to facilitate downstream filtering. We have carefully designed validation experiments and performed extensive comparison and analysis to show the efficiency and effectiveness of RED-ML under different conditions, and it can accurately detect novel RNA editing sites without relying on curated RNA editing databases. We have also made this tool freely available via GitHub . We have developed a highly accurate, speedy and general-purpose tool for RNA editing detection using RNA-seq data. With the availability of RED-ML, it is now possible to conveniently make RNA editing a routine analysis of RNA-seq. We believe this can greatly benefit the RNA editing research community and has profound impact to accelerate our understanding of this intriguing posttranscriptional modification process.

Erratum: General Non-Markovian Dynamics of Open Quantum Systems [Phys. Rev. Lett. 109, 170402 (2012)].

This corrects the article DOI: 10.1103/PhysRevLett.109.170402.

Quantum control of spin-nematic squeezing in a dipolar spin-1 condensate.

Versatile controllability of interactions and magnetic field in ultracold atomic gases ha now reached an era where spin mixing dynamics and spin-nematic squeezing can be studied. Recent experiments have realized spin-nematic squeezed vacuum and dynamic stabilization following a quench through a quantum phase transition. Here we propose a scheme for storage of maximal spin-nematic squeezing, with its squeezing angle maintained in a fixed direction, in a dipolar spin-1 condensate by applying a microwave pulse at a time that maximal squeezing occurs. The dynamic stabilization of the system is achieved by manipulating the external periodic microwave pulses. The stability diagram for the range of pulse periods and phase shifts that stabilize the dynamics is numerical simulated and agrees with a stability analysis. Moreover, the stability range coincides well with the spin-nematic vacuum squeezed region which indicates that the spin-nematic squeezed vacuum will never disappear as long as the spin dynamics are stabilized.

Characterization of RNA editome in primary and metastatic lung adenocarcinomas.

RNA editing results in post-transcriptional modification and could potentially contribute to carcinogenesis. However, RNA editing in advanced lung adenocarcinomas has not yet been studied. Based on whole genome and transcriptome sequencing data, we identified 1,071,296 RNA editing events from matched normal, primary and metastatic samples contributed by 24 lung adenocarcinoma patients, with 91.3% A-to-G editing on average, and found significantly more RNA editing sites in tumors than in normal samples. To investigate cancer relevant editing events, we detected 67,851 hyper-editing sites in primary and 50,480 hyper-editing sites in metastatic samples. 46 genes with hyper-editing in coding regions were found to result in amino acid alterations, while hundreds of hyper-editing events in non-coding regions could modulate splicing or gene expression, including genes related to tumor stage or clinic prognosis. Comparing RNA editome of primary and metastatic samples, we also discovered hyper-edited genes that may promote metastasis development. These findings showed a landscape of RNA editing in matched normal, primary and metastatic tissues of lung adenocarcinomas for the first time and provided new insights to understand the molecular characterization of this disease.

Single-cell RNA sequencing reveals dynamic changes in A-to-I RNA editome during early human embryogenesis.

BACKGROUND: A-to-I RNA-editing mediated by ADAR (adenosine deaminase acting on RNA) enzymes that converts adenosine to inosine in RNA sequence can generate mutations and alter gene regulation in metazoans. Previous studies have shown that A-to-I RNA-editing plays vital roles in mouse embryogenesis. However, the RNA-editing activities in early human embryonic development have not been investigated. RESULTS: Here, we characterized genome-wide A-to-I RNA-editing activities during human early embryogenesis by profiling 68 single cells from 29 human embryos spanning from oocyte to morula stages. We demonstrate dynamic changes in genome-wide RNA-editing during early human embryogenesis in a stage-specific fashion. In parallel with ADAR expression level changes, the genome-wide A-to-I RNA-editing levels in cells remained relatively stable until 4-cell stage, but dramatically decreased at 8-cell stage, continually decreased at morula stage. We detected 37 non-synonymously RNA-edited genes, of which 5 were frequently found in cells of multiple embryonic stages. Moreover, we found that A-to-I editings in miRNA-targeted regions of a substantial number of genes preferably occurred in one or two sequential stages. CONCLUSIONS: Our single-cell analysis reveals dynamic changes in genome-wide RNA-editing during early human embryogenesis in a stage-specific fashion, and provides important insights into early human embryogenesis.

Recent Advances in the Synthesis of SCF2 H- and SCF2 FG-Containing Molecules.

In recent years, much interest has been paid to difluoromethylthiolated molecules as the "SCF2 " moiety is a key motif in drug and agrochemical research. Consequently, the development of versatile strategies for the selective synthesis of SCF2 H- and SCF2 FG-containing molecules (FG=functional group) has attracted a lot of attention and inspired the scientific community to design new tools. This Minireview highlights the major progress made in this field. Particularly, methodologies developed for the difluoromethylation of sulfur-containing molecules and the direct construction of C-SCF2 bonds in various classes of compounds are showcased and discussed.