Differences in tourism economic development and its influencing factors among three major city clusters along the middle reaches of the Yangtze River.

An in-depth study of the mechanisms governing the generation, evolution, and regulation of differences in tourism economics holds significant value for the rational utilization of tourism resources and the promotion of synergistic tourism economic development. This study utilizes mathematical statistical analysis and GIS spatial analysis to construct a single indicator measure and a comprehensive indicator measure to analyze tourism-related data in the research area from 2004 to 2019. The main factors influencing the spatial and temporal differences in the tourism economy are analyzed using two methods, namely, multiple linear regression and geodetector. The temporal evolution, overall differences and differences within each city group fluctuate downwards, while the differences between groups fluctuate upwards. Domestic tourism economic differences contribute to over 90% of the overall tourism economic differences. Spatial divergence, the proportion of the tourism economy accounted for by spatial differences is obvious, the comprehensive level of the tourism economy can be divided into five levels. The dominant factors in the formation of the pattern of spatial and temporal differences in the tourism economy are the conditions of tourism resources based on class-A tourist attractions and the level of tourism industry and services based on star hotels and travel agencies. This study addresses the regional imbalance of tourism economic development in city clusters and with the intent of promoting balanced and high-quality development of regional tourism economies.

Catalytic Asymmetric Hydroacyloxylation/Ring-Opening Reaction of Ynamides, Acids, and Aziridines.

A highly enantioselective three-component reaction of ynamides with carboxylic acids and 2,2'-diester aziridines has been realized by using a chiral N,N'-dioxide/Ho(OTf)3 complex as a Lewis acid catalyst. The process includes the formation of an α-acyloxyenamide intermediate through the addition of carboxylic acids to ynamides and the following enantioselective nucleophilic addition to in-situ-generated azomethine ylides induced by the chiral catalyst. A range of amino acyloxyenamides are delivered in moderate to good yields with good ee values. In addition, a possible catalytic cycle with a transition model is proposed to elucidate the reaction mechanism.

Catalytic Asymmetric Acyloin Rearrangements of α-Ketols, α-Hydroxy Aldehydes, and α-Iminols by N,N'-Dioxide-Metal Complexes.

A highly enantioselective acyloin rearrangement of cyclic α-ketols has been developed with a chiral Al(III)-N,N'-dioxide complex as catalyst. This strategy provided an array of optically active 2-acyl-2-hydroxy cyclohexanones in moderate to good yields with high enantioselectivities. The asymmetric isomerizations of acyclic α-hydroxy aldehydes and α-iminols were achieved as well under modified conditions, affording the corresponding chiral α-hydroxy ketones and α-amino ketones in moderate results. Moreover, further transformations of product to enantioenriched diols were carried out.

Catalytic Asymmetric Three-component Hydroacyloxylation/ 1,4-Conjugate Addition of Ynamides.

A highly enantioselective three-component hydroacyloxylation/1,4-conjugate addition of ortho-hydroxybenzyl alcohols, ynamides and carboxylic acids was developed under mild reaction conditions in the presence of a chiral N,N'-dioxide/Sc(OTf)3 complex, which went through in situ generated ortho-quinone methides with α-acyloxyenamides, delivering a range of corresponding chiral α-acyloxyenamides derivatives containing gem(1,1)-diaryl skeletons in moderate to good yields with excellent ee values. The scale-up experiment and further derivation showed the practicality of this catalytic system. In addition, a possible catalytic cycle and transition state model was proposed to elucidate the origin of the stereoselectivity based on X-ray crystal structure of the α-acyloxyenamide intermediate and product.

Divergent Synthesis of Enantioenriched ß-Functional Amines via Desymmetrization of meso-Aziridines with Isocyanides.

A highly enantioselective ring-opening desymmetrization of meso-aziridines with isocyanides was achieved in the presence of a chiral N,N'-dioxide/Mg(OTf)2 complex. The in situ generated chiral 1,4-zwitterionic intermediates were successfully trapped by intramolecular oxygen- and carbon-based nucleophiles or exogenous H2O and TMSN3, enabling a collective synthesis of various chiral vicinal amino-oxazoles, spiroindolines, ß-amino amides, and tetrazole derivative in moderate to high yields with excellent enantioselectivities.

Nickel(II)-Catalyzed Enantioselective α-Vinylation of ß-Keto Amides/Esters with Hypervalent Iodine Salts.

The enantioselective α-vinylation of ß-keto amides/esters using hypervalent iodine salts has been accomplished via a chiral N,N'-dioxide-nickel(II) complex promoted electrophilic addition and reductive elimination process. A wide range of vinyl-substituted all-carbon quaternary ß-keto amides/esters were obtained in high yields and ee values (up to 99% yield and 99% ee). Moreover, the catalytic system has been applied to the enantioselective alkynylation/arylation of ß-ketoamides with good results.

Nickel(ii)-catalyzed enantioselective cyclopropanation of 3-alkenyl-oxindoles with phenyliodonium ylide via free carbene.

A chiral Lewis acid-promoted enantioselective cyclopropanation using phenyliodonium ylide as the carbene precursor was developed. A variety of spirocyclopropane-oxindoles with contiguous tertiary and all carbon quaternary centers were obtained in excellent outcomes (up to 99% yield, >19 : 1 d.r., up to 99% ee). EPR spectroscopy study supported a stepwise biradical mechanism.

Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery.

The advent of powerful genomics technologies has uncovered many fundamental aspects of biology, including the mechanisms of cancer; however, it has not been appropriately matched by the development of global approaches to discover new medicines against human diseases. Here we describe a unique high-throughput screening strategy by high-throughput sequencing, referred to as HTS(2), to meet this challenge. This technology enables large-scale and quantitative analysis of gene matrices associated with specific disease phenotypes, therefore allowing screening for small molecules that can specifically intervene with disease-linked gene-expression events. By initially applying this multitarget strategy to the pressing problem of hormone-refractory prostate cancer, which tends to be accelerated by the current antiandrogen therapy, we identify Peruvoside, a cardiac glycoside, which can potently inhibit both androgen-sensitive and -resistant prostate cancer cells without triggering severe cytotoxicity. We further show that, despite transcriptional reprogramming in prostate cancer cells at different disease stages, the compound can effectively block androgen receptor-dependent gene expression by inducing rapid androgen receptor degradation via the proteasome pathway. These findings establish a genomics-based phenotypic screening approach capable of quickly connecting pathways of phenotypic response to the molecular mechanism of drug action, thus offering a unique pathway-centric strategy for drug discovery.