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.

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.

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.

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.

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.

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).

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.

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.

An Electrophilic Reagent for the Direct Introduction of the SCF2 PO(OEt)2 Group to Molecules.

An unprecedented electrophilic difluoromethylthiolating reagent (MesNHSCF2 PO(OEt)2 ) was designed. Under mild and metal-free conditions, this new reagent reacted with various nucleophiles, thus offering an efficient and operationally simple tool for the construction of C-SCF2 PO(OR)2 , N-SCF2 PO(OR)2 , and S-SCF2 PO(OR)2 bonds. Finally, thanks to this new methodology, the synthesis of the non-stereoidal anti-inflammatory diflumidone was achieved.

Spatial features for Escherichia coli genome organization.

BACKGROUND: In bacterial genomes, the compactly encoded genes and operons are well organized, with genes in the same biological pathway or operons in the same regulon close to each other on the genome sequence. In addition, the linearly close genes have a higher probability of co-expression and their protein products tend to form protein-protein interactions. However, the organization features of bacterial genomes in a three-dimensional space remain elusive. The DNA interaction data of Escherichia coli, measured by the genome conformation capture (GCC) technique, have recently become available, which allowed us to investigate the spatial features of bacterial genome organization. RESULTS: By renormalizing the GCC data, we compared the interaction frequency of operon pairs in the same regulon with that of random operon pairs. The results showed that arrangements of operons in the E. coli genome tend to minimize the spatial distance between operons in the same regulon. A similar global organization feature exists for genes in biological pathways of E. coli. In addition, the genes close to each other spatially (even if they are far from each other on the genome sequence) tend to be co-expressed and form protein-protein interactions. These results provided new insights into the organization principles of bacterial genomes and support the notion of transcription factory. CONCLUSIONS: This study revealed the organization features of Escherichia coli genomic functional units in the 3D space and furthered our understanding of the link between the three-dimensional structure of chromosomes and biological function.

Palladium(II)-catalyzed directed trifluoromethylthiolation of unactivated C(sp³)-H bonds.

The synthesis of trifluoromethylthiolated aliphatic acid derivatives by Pd-catalyzed C(sp(3))-H bond functionalization was developed. Using a bidentate directing group, the direct and selective introduction of a SCF3 moiety was possible on a range of amides with remarkable selectivity for C(sp(3))-centers with an electrophilic SCF3 source and pivalic acid as an additive. This work constitutes an example of the unactivated C(sp(3))-SCF3 bond formation by C-H activation offering a new access to relevant molecules.

Copper-catalyzed one-pot denitrogenative-dehydrogenative-decarboxylative coupling of ß-ketoacids with trifluorodiazoethane: facile access to trifluoromethylated aldol products.

A novel copper-catalyzed one-pot cross-coupling of ß-ketoacids with in situ generated trifluorodiazoethane has been developed. This reaction provides a direct and efficient method, in which one C-C bond and one C-O bond were formed in a carbenoid center with concomitant denitrogenation-dehydrogenation-decarboxylation, to afford trifluoromethylated aldol products. In several preliminary experiments, good to high enantioselectivities were also obtained.

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.

Organocatalytic asymmetric one-pot sequential conjugate addition/dearomative fluorination: synthesis of chiral fluorinated isoxazol-5(4H)-ones.

A facile one-pot sequential conjugate addition/dearomative fluorination transformation of isoxazol-5(4H)-ones with nitroolefins and N-fluorobenzenesulfonimide (NFSI) has been developed. By using a bifunctional chiral tertiary amino-thiourea catalyst, a series of chiral fluorinated isoxazol-5(4H)-ones containing one fluorine-substituted quarternary stereocenter were obtained in high yields with high enantio- and diastereoselectivities. Further transformation of adducts could afford isoxazolidin-5-one derivatives with three contiguous stereocenters.

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.

General non-Markovian dynamics of open quantum systems.

We present a general theory of non-Markovian dynamics for open systems of noninteracting fermions (bosons) linearly coupled to thermal environments of noninteracting fermions (bosons). We explore the non-Markovian dynamics by connecting the exact master equations with the nonequilibirum Green's functions. Environmental backactions are fully taken into account. The non-Markovian dynamics consists of nonexponential decays and dissipationless oscillations. Nonexponential decays are induced by the discontinuity in the imaginary part of the self-energy corrections. Dissipationless oscillations arise from band gaps or the finite band structure of spectral densities. The exact analytic solutions for various non-Markovian thermal environments show that non-Markovian dynamics can be largely understood from the environmental-modified spectra of open systems.

Asymmetric phase-transfer-catalyzed conjugate addition of glycine imine to exocyclic α,ß-unsaturated ketones: construction of polycyclic imines containing three stereocenters.

We developed a facile, one-pot, multistep transformation between glycine imine and exocyclic α,ß-unsaturated ketones in reactions catalyzed by chiral phase-transfer catalysts (PTC). A series of polycyclic imines containing three adjacent stereocenters were obtained in good to high yields with high diastereo- and enantioselectivities. Further transformation of the imines could afford N-fused polycyclic compounds with four adjacent stereocenters.

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.

Non-Markovian dynamics of a microcavity coupled to a waveguide in photonic crystals.

In this paper, the non-Markovian dynamics of a microcavity coupled to a waveguide in photonic crystals is studied based on a semi-finite tight binding model. Using the exact master equation, we solve analytically and numerically the general and exact solution of the non-Markovain dynamics for the cavity coupled to the waveguide in different coupling regime. A critical transition is revealed when the coupling increases between the cavity and the waveguide. In particular, the cavity field becomes dissipationless when the coupling strength goes beyond a critical value, as a manifestation of strong non-Markovian memory effect. The result also indicates that the cavity can maintain in a coherent state with arbitrary small number of photons when it strongly couples to the waveguide at very low temperature. These properties can be measured experimentally through the photon current flowing over the waveguide in photonic crystals.