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Herein, we report a bromide-mediated, C2-selective, and oxygenative alkylation of pyridinium salts using alkenes and O2 for the synthesis of biologically important β-2-pyridyl ketones.

A 2-pyridyl-alkylation of benzyne using N-alkylpyridinium salts has been developed under either photochemical or thermal conditions. This metal-free dicarbofunctionalization of benzyne undergoes a de Mayo-type process including cascade dearomative [3+2] cycloaddition and rearomative ring-opening reaction. An electron-deficient N-cyclic alkyl group was necessary. A formal ortho-C–H arylation of pyridine has been achieved.

ObjectivesTo develop, validate, and evaluate a predictive model for breast cancer diagnosis using conventional ultrasonography (US), shear wave elastography (SWE), and contrast-enhanced US (CEUS).Materials and methodsThis retrospective study included 674 patients with 674 breast lesions. The data, a main and an independent datasets, were divided into three cohorts. Cohort 1 (80% of the main dataset; n = 448) was analyzed by logistic regression analysis to identify risk factors and establish the predictive model. The area under the receiver operating characteristic curve (AUC) was analyzed in Cohort 2 (20% of the main dataset; n = 119) to validate and in Cohort 3 (the independent dataset; n = 107) to evaluate the predictive model.ResultsMultivariable regression analysis revealed nine independent breast cancer risk factors, including age > 40 years; ill-defined margin, heterogeneity, rich blood flow, and abnormal axillary lymph nodes on US; enhanced area enlargement, contrast agent retention, and irregular shape on CEUS; mean SWE higher than the cutoff value (P < 0.05 for all). The diagnostic performance of the model was good, with AUC values of 0.847, 0.857, and 0.774 for Cohorts 1, 2, and 3, respectively. The model increased the diagnostic specificity (from 31% to 81.3% and 7.3% to 73.1% in cohorts 2 and 3, respectively) without a significant loss in sensitivity (from 100.0% to 90.1% and 100.0% to 81.8% in cohorts 2 and 3, respectively).ConclusionThe multi-parameter US-based model showed good performance in breast cancer diagnosis, improving specificity without a significant loss in sensitivity. Using the model could reduce unnecessary biopsies and guide clinical diagnosis and treatment.

A simple and practical visible-light-induced carbo-2-pyridylation of electron-deficient alkenes with readily available N-benzoylmethylpyridinium bromides is reported. More than 40 examples are presented and proceed in greater than 80 % yield (on average) with excellent regio- and diastereoselectivities.

With H2WO4 as the catalyst and H2O2 as the oxidant, we herein report a deconstructive difunctionalization of the C-N bond in unstrained, benzo cyclic amines to generate an ester group and nitro group simultaneously. The preliminary mechanistic studies suggested that the corresponding hydroxamic acid is the key intermediate for this transformation. Importantly, with the utilization of this transformation, we achieved an interesting approach for the ring contraction of quinoline to indole, an example of scaffold hopping in a hetero-aromatic system.

Thanks to the facile imine-enamine tautomerization, the β,γ-unsaturated hydrazones have been successfully utilized as surrogates of aminodienes for realizing the Pd-catalyzed tandem aminomethylamination/aromatization reaction with aminals via C-N bond activation. This direct and operationally simple protocol provides a fundamentally novel strategy to synthesize aromatic heterocycles from alkenes in the absence of external oxidant and base. Mechanistic studies suggested that aminal not only functioned as an aminomethyl source but also acted as formal oxidant and inner base to promote the aromatization.

Gold-catalyzed intermolecular propargyl alcohol addition to alkyne was achieved. The reaction of propargyl alcohol with a typical gold catalyst gave the hydration product almost exclusively. The triazole gold catalyst (TA-Au) successfully prevented the hydration, giving the vinyl ether followed by a 3,3-rearrangement. Synthetically useful substituted allenes were formed with high efficiency, substrate tolerability and chemoselectivity. Also, more than 95% chirality transfer from propargyl alcohol to allene was obtained.

An efficient synthesis of substituted cyclopentenes through gold/gallium-catalyzed annulation of 1,3-dicarbonyl compounds and cyclopropylacetylenes is achieved. This tandem reaction consists of a gold-catalyzed Nakamura reaction, a catalytic dienol–enone tautomerization, and a gallium-catalyzed vinylcyclopropane (VCP) rearrangement.

Using a combination of triazole-gold (TA-Au) and copper catalysts, the substituted furan was achieved in one pot through a three-step reaction cascade. The reaction tolerates a large substrate scope with simple starting materials. The desired di-, tri-, and tetrasubstituted furans were prepared in good to excellent yields.

A gold-catalyzed nitrogenation of alkynes for the synthesis of carbamides and amino tetrazoles through C-C and C≡C bond cleavages is described. A diverse set of functionalized carbamide and amino tetrazole derivatives were selectively constructed under mild conditions. The chemoselectivity can be easily switched by the selection of the acid additives. The reaction is characterized by its broad substrate scope, direct construction of high value products, easy operation under air, and mild conditions at room temperature. This chemistry provides a way to transform alkynes by splitting the substrate into three parts.

Fluorescence active fused-triazole was developed as a ligand in gold(I) cation coordination. The coordination ability was evaluated using NMR and fluorescence emission. Our previously reported N-2-aryl-triazoles, though gave good emission, could not form stable complexes with gold cations. A new N-fused-triazole (NFT) derivative was prepared and the ligand indicated good fluorescence emission, and formed strong coordination with gold cations. Both ligand and complex were characterized by X-ray crystallography. Fluorescence properties of various gold complexes (with different primary ligands) were evaluated, which suggested the feasibility of using fluorescence emission as potential tools for future mechanistic investigation.

Gold-catalyzed alkyne hydration was studied by using in situ reacting mass spectrometry (MS) technology. By monitoring the reaction process in solution under different conditions (regular and very diluted catalyst concentrations, different pH values) and examining the reaction occurrence in the early reaction stage (1-2 ms after mixing) with MS, we collected a series of experimental evidence to support that the bis-gold complex is a potential key reaction intermediate. Furthermore, both experimental and computational studies confirmed that the σ,π-bis-gold complexes are not active intermediates toward nucleophilic addition. Instead, formation of geminally diaurated complex C is crucial for this catalytic process.

An unexpected ligand effect was discovered in the silver(I)-catalyzed alkyne activation. For both aldehyde-alkyne-amine (A3) condensation and intermolecular alkyne hydroamination, the type B complex (P:Ag=1:1) effectively promoted the reaction, while no reaction occurred with either no ligand or excess ligands under the identical conditions.

A method for the direct synthesis of substituted alcohols, ketones, and diketones through a catalyst-controlled highly chemoselective coupling and oxygenation of olefins is developed.

The aim of this study was to evaluate the application of acoustic radiation force impulse (ARFI) ultrasound imaging and its potential value in the characterization of cervical cancer. ARFI ultrasound imaging of the uterine cervix was performed in 58 patients with cervical cancer prior to surgery. The diagnosis of cervical cancer was confirmed by pathological results in each case. eSie Touch elastography imaging (EI), Virtual Touch tissue imaging (VTI) and Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions, Mountain View, CA, USA) were used to qualitatively and quantitatively analyze the elasticity and hardness of lesions. For statistical analysis, the non-parametric Mann-Whitney U test and the Student’s u test were used to compare the elastic parameters and the results. EI showed that, compared with the surrounding cervical tissue, 72.41% (42 of 58) of the malignant lesions showed 4th or 5th grade images and 27.59% (16 of 58) had 3rd grade images. The EI images showed a significant difference between the malignant lesions and the surrounding normal tissues (P

We describe herein a gold-catalyzed rearrangement of propargyl esters followed by allene–ene cyclization to afford substituted bicyclic [4.4.0] dihydronaphthalene compounds. This method is also applied to vinylethers and vinylamines of 1,7-enyne esters to form dihydroquinoline and dihydrobenzopyran structures. The basis of this transformation is the ligand-controlled preferential activation of the alkene over the allene, affording the desired aromatic bicyclic structures in moderate to excellent yields.

An efficient synthesis of substituted cyclopentenes through gold/gallium-catalyzed annulation of 1,3-dicarbonyl compounds and cyclopropylacetylenes is achieved. This tandem reaction consists of a gold-catalyzed Nakamura reaction, a catalytic dienol–enone tautomerization, and a gallium-catalyzed vinylcyclopropane (VCP) rearrangement.

We describe herein a gold-catalyzed rearrangement of propargyl esters followed by allene–ene cyclization to afford substituted bicyclic [4.4.0] dihydronaphthalene compounds. This method is also applied to vinylethers and vinylamines of 1,7-enyne esters to form dihydroquinoline and dihydrobenzopyran structures. The basis of this transformation is the ligand-controlled preferential activation of the alkene over the allene, affording the desired aromatic bicyclic structures in moderate to excellent yields.

Gold-catalyzed intermolecular propargyl alcohol addition to alkyne was achieved. The reaction of propargyl alcohol with a typical gold catalyst gave the hydration product almost exclusively. The triazole gold catalyst (TA–Au) successfully prevented the hydration, giving the vinyl ether followed by a 3,3-rearrangement. Synthetically useful substituted allenes were formed with high efficiency, substrate tolerability and chemoselectivity. Also, more than 95% chirality transfer from propargyl alcohol to allene was obtained.

An efficient gold-catalyzed process that involves the cleavage of one C—C single bond and the triple bond of alkynes (I) and (III) is described.

Compared with other transition metals, copper and iron saltsare inexpensive and stable to air and moisture. Moreover, iron isconsidered as an environmentally friendly catalyst. Due to these benigncharacteristics, both copper and iron catalysis have been extensively- investigated.More recently, inexpensive copper/iron-cocatalyzed reactionshave presented an attractive prospect for organic synthesis. Thisreview presents recent progress in copper/iron-cocatalyzedarylation, alkynylation, C-H functionalization, and conjugateaddition reactions. 1 Introduction 2 Arylation Reactions 2.1 C-N Bond Formation 2.2 C-O Bond Formation 2.3 C-S Bond Formation 2.4 Summary 3 Alkynylation Coupling Reactions 3.1 Sonogashira-Type Reactions 3.2 Glaser-Type Coupling 4 C-H Functionalization 5 Conjugate Addition Reactions 6 Conclusion

A novel, efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature has been disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.

Transition-metal catalysed C-N bond activation has attracted much attention and become one of the most promising bond disconnection and formation strategies that encompass a broad spectrum of applications in many reactions. In this tutorial review, efficient strategies for catalytic cleavage of C(sp)-N, C(sp(2))-N and C(sp(3))-N bonds and their applications in new C-C and C-N bond formation reactions are summarized.

Objective The digital human modeling combines information technology with bioscience, applied to analog study from DNA molecule and protein to cell and tissue, as well as organ. It has been widely implemented in various fields such as aviation, national defense, film and television, sports and medical treatment. This paper sorts relative research achievements and progress in recent years and summarizes issues and challenges of research work. The purpose of this paper is to provide references for the development of Digital Human Modeling. Methods Basing on the development plans proposed by Federation of American Scientists (FAS) and current theories, we sorted academic achievements and relative references since the beginning of the digital human concept until 2014 into four aspects, which were named as Visible Human, Virtual Physical Human, Virtual Physiological Human, and Intelligent Virtual Human. We collected information of data acquisition, data analysis and dataset establishment for Visible Human. We outlined the Virtual Physical Human references in four physical categories, including radiation, ultrasonic, electrics, and mechanics. For Virtual Physiological Human, relative researches related to the physiological and biochemical changes of human body were categorized in four aspects as gene molecules, cells, and organs. Relative researches of Virtual Brain Human were mainly concentrated on virtual human brain and virtual human control. Results According to the differences in investigations and applications requirements of Digital Human in all aspects, we classified, analyzed and concluded extensive preference data. The overall plan of Digital Human, as well as technical routes, work plans, present states, goals, results and application value in each stage of research was summarized. We discussed the technical issues existing in each aspect of Digital Human, along with the urgent key technologies including data collection, data processing, and modeling. Conclusion Analyzing the core technologies and the general technical schemes in the field of Digital Human, this paper summarizes the technical solutions, research results and technical problems of major researchers. The future prospects of Digital Human are reviewed.

Radical addition to vinyltriazole was developed as a new approach to achieve 1,2,3-triazole ring opening under mild conditions. Through reagent control, excellent chemoselectivity was achieved, giving either nitrile under basic conditions or quinoxaline under neutral conditions. Reactivities made this method an attractive new reaction mode.

Along with the development of computer technologies and digitization of human body's information, the digital human entered into a new stage of modelling physical features from the stage of reconstructing anatomical structures. By summarizing domestic and abroad relevant documents, we in this paper present the general scheme of digital human and the location of physical human as well as its conception and applied value. We especially analyze the modeling process of physical human, core technologies and its research and applications in four main fields: electromagnetic radiation, ultrasound propagation, bioimpedance measurements and biomechanical analysis. We also analyze and summarize existing problems of present physical human model and point out the future development trends of physical human.

The triazole-gold(I) complex catalyzed [3,3]-rearrangement of propargyl ester has been quantitatively investigated through in situ IR. First order dependence of the initial rates on [Au] and [propargyl ester] suggested that the turnover-limiting step is the associative ligand substitution. The activation enthalpy was also determined to be 7.8 kcal mol(-1). TA-Au catalysts with different triazole derivatives were also tested, giving a linear free energy relationship with a ρ value of 0.74.

Radical addition to vinyltriazole was developed as a new approach to achieve 1,2,3-triazole ring opening under mild conditions. Through reagent control, excellent chemoselectivity was achieved, giving either nitrile under basic conditions or quinoxaline under neutral conditions. Reactivities made this method an attractive new reaction mode.

A gold-catalyst with an electron-deficient phosphite as the ancillary ligand is found to exclusively promote the carbophilic chemoselective addition of arenes, hetarenes and 1,3-diketones to α-aryldiazoesters.

Chiral piperidines are prepared in a one-pot procedure from enones, nitroolefines, and chiral amines.

The optimized procedure can be applied to various aryl ketones and best results concerning the yields are obtained with a second keto group at the β-position of the substrate.

In the presence of silver only trace amounts of the cycloaddition products are obtained, therefore the silver-free condition is critical for this reaction.

This Ag-catalysis is based on a strong ligand effect requiring a ratio of BINAP:Ag of 1:2 for excellent yields and moderate enantioselectivities.

A simple ceric ammonium nitrate (CAN) catalyzed functionalization of ketones through double C–C bond cleavage strategy has been disclosed. This reaction provides a mild, practical method toward carbamoyl azides, which are versatile intermediates and building blocks in organic synthesis. Based on relevant mechanistic studies, a unique and plausible C–C bond and N–O bond cleavage process is proposed, where the oxyamination intermediate plays an important role in this reaction.

The chemoselective addition of arenes and 1,3-diketones to α-aryldiazoesters was achieved through ligand-controlled gold catalysis. Unlike a dirhodium catalyst (which promotes C(sp3)-H insertion and cyclopropanation) and a copper catalyst (which catalyzes O-H and N-H insertions), the gold catalyst with an electron-deficient phosphite as the ancillary ligand exclusively gave the carbophilic addition product, thus representing a new and efficient approach to form "carbophilic carbocations", which selectively react with carbon nucleophiles.

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

A method for the direct synthesis of substituted alcohols, ketones, and diketones through a catalyst-controlled highly chemoselective coupling and oxygenation of olefins is developed.

The specific and efficient delivery of small interfering RNA (siRNA) into cancer cells in vivo remains a major obstacle. In this study, we investigated whether ultrasound-targeted microbubble destruction (UTMD) combined with dual targeting of HSP72 and HSC70 in prostate cancer cell lines improve the specific and efficient cell uptake of siRNA, inhibit HSP90 function and induce extensive tumor-specific apoptosis. VCaP cells were transfected with siRNA oligonucleotides. Cell viability assays were used to evaluate the safety of UTMD. The expression of HSP70, HSP90, caspase-8, caspase-3, PARP-1 and cleaved caspase-3 were determined by quantitative PCR and western blotting. Apoptosis and transfection efficiency were detected by flow cytometry. We found that HSP72, HSC70 and HSP90 expression was absent or weak in normal prostate epithelial cells (RWPE-1), and became uniformly and strongly expressed in prostate cancer cells (VCaP). VCaP and RWPE-1 cells expressed very low levels of caspase-8, caspase-3, PARP-1 and cleaved caspase-3. UTMD combined with dual targeting of HSP72 and HSC70 siRNA impoved the efficiency of transfection, cell uptake of siRNA, downregulated HSP70 and HSP90 expression in VCaP cells on the mRNA and protein levels, and upregulated major apoptotic markers (PARP-1, caspase-8, caspase-3 and cleaved caspase-3), thus, inducing extensive tumor-specific apoptosis. The Cell Counting Kit-8 assay showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting of HSP72 and HSC70 may improve the specific and efficient cell uptake of siRNA, inhibit HSP90 function and induce extensive tumor-specific apoptosis, indicating a novel, potential means for targeting therapeutic strategy to prostate cancer cells.

A novel, efficient oxidation of α-aryl halogen derivatives to the corresponding α-aryl carbonyl compounds at room temperature has been disclosed. Natural sunlight and air are successfully utilized in this approach through the combination of photocatalysis and organocatalysis. A plausible mechanism was proposed on the basis of the mechanistic studies.

Surfactants with a polycyclic aromatic moiety and a long hydrocarbon chain, carbazole-tailed amphiphilic imidazolium ionic liquids 1-[n-(N-carbazole)alkyl]-3-methylimidazolium bromide [CzC(n)MIm]Br (n=10 and 12), were designed to disperse carbon nanotubes (CNTs) in aqueous solutions. UV-vis-NIR spectra were performed to determine the dispersion of CNTs and the optimal concentration (C(opt)) of [CzC(n)MIm]Br. Compared with [C(n)MIm]Br, [CzC(n)MIm]Br was more effective with the smaller C(opt) and more individual CNTs, reflecting the effect of the carbazole moiety. The adsorption of [CzC(n)MIm]Br molecules on CNTs was investigated by zeta-potential, surface tension, fluorescence, and (1)H NMR. Having zeta-potentials higher than 15mV contributed to the long-term stability of aqueous CNT dispersions. The significant fluorescence quenching and the upfield shift of carbazole protons support the π-π stacking interaction between carbazole moieties and the π-networks of CNTs. Meanwhile, the upfield shift of imidazolium protons indicates the cation-π interaction between the imidazolium ions and the π-networks of CNTs.

A ligand-free Pd-catalyzed highly selective oxidative Heck reaction of organoboronic acids with allyl esters was developed. β-H elimination is highly chemoselectively controlled, leading to γ-substituted allyl esters, which is contrary to the traditional Heck-type reactions of allyl esters. Moreover, the regio- and stereoselectivities are also high due to the chelation between O and Pd atoms.

Three amphiphilic imidazolium ionic liquids (ILs), 1-[n-(N-carbazole)alkyl]-3-methylimidazolium bromide [carbazoleC(n)mim]Br (n = 6, 10, and 12), that incorporate a fluorescent carbazole moiety at the terminal of the hydrocarbon chain, were designed and synthesized. Their surface activity, aggregation behavior, and thermodynamics of micelle formation in aqueous solutions were systematically investigated by surface tension, electrical conductivity, and (1)H NMR spectroscopy. The incorporation of bulky carbazole groups led to the loose arrangement of [carbazoleC(n)mim]Br molecules at the air-water interface. Both the enhanced hydrophobicity and the pi-pi interaction due to the incorporation of carbazole groups contributed to the lower critical micelle concentration (cmc) and higher micellar aggregation number, reflecting a strong capability of the designed carbazole-tailed imidazolium ILs for the formation of micelle. The analysis of (1)H NMR spectra revealed that the carbazole moieties may overlap with the middle methylenes of the alkyl chains. The amphiphilic carbazole-tailed imidazolium ILs demonstrated strong and stable fluorescence properties, indicating their potential application in the combined field of surface chemistry and photochemistry.