Publications by authors named "Baohua Chen"

48 Publications

Chromosome-level genome of Poropuntius huangchuchieni provides a diploid progenitor-like reference genome for the allotetraploid Cyprinus carpio.

Mol Ecol Resour 2021 Jul 4;21(5):1658-1669. Epub 2021 Mar 4.

State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, China.

The diploid Poropuntius huangchuchieni in the cyprinid family, which is widely distributed in the Mekong and Red River basins, is one of the most closely related diploid progenitor-like species of allotetraploid common carp, which was generated by merging of two diploid genomes during evolution. Therefore, the P. huangchuchieni genome is essential for polyploid evolution studies in Cyprinidae. Here, we report a high-quality chromosome-level genome assembly of P. huangchuchieni by integrating Oxford Nanopore and Hi-C technologies. The assembled genome size was 1,021.38 Mb, 895.66 Mb of which was anchored onto 25 chromosomes with a N50 of 32.93 Mb. The genome contained 486.28 Mb repetitive elements and 24,099 protein-coding genes. Approximately 95.9% of the complete BUSCOs were detected, suggesting a high completeness of the genome. Evolutionary analysis revealed that P. huangchuchieni diverged from Cyprinus carpio at approximately 12 Mya. Genome comparison between P. huangchuchieni and the B subgenome of C. carpio provided insights into chromosomal rearrangements during the allotetraploid speciation. With the complete gene set, 17,474 orthologous genes were identified between P. huangchuchieni and C. carpio, providing a broad view of the gene component in the allotetraploid genome, which is critical for future genetic analyses. The high-quality genomic data set created for P. huangchuchieni provides a diploid progenitor-like reference for the evolution and adaptation of allotetraploid carps.
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http://dx.doi.org/10.1111/1755-0998.13365DOI Listing
July 2021

Genome-wide identification and characterization of olfactory receptor genes in common carp (Cyprinus carpio).

Gene 2021 Apr 2;777:145468. Epub 2021 Feb 2.

Fujian Key Laboratory of Genetics and Breeding of Marine Organisms, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China. Electronic address:

The environment contains a large extent of chemical information, which could be detected as olfactory sense. Olfactory in vertebrates plays important roles on many aspects during life time, including localizing prey or food, avoiding predators, mating behavior and social communication. Considering the essential role of olfactory receptors in the specific recognition of diverse stimuli, understanding the evolutionary dynamics of olfactory receptors in teleost means a lot, especially in the allotetraploid common carp, who has undergone the fourth whole-genome duplication event. Here, we identified the whole set of olfactory receptor genes in representative teleosts and found a significant contraction in common carp when compared with other teleosts. Odorant receptor genes (OR) occupy the most among four groups of olfactory receptors, including 33 functional genes and 16 pseudogenes. Furthermore, 6 trace amine-associated receptor (TAAR) genes (including 1 pseudogene), 7 odorant-related-A receptor genes, and 10 olfactory C family receptor genes (including 3 pseudogenes) were identified in common carp. Phylogenetic and motif analysis were performed to illustrate the phylogenetic relationship and structural conservation of teleost olfactory receptors. Selection pressure analysis suggested that olfactory receptor groups in common carp were all under relaxed purifying-selection. Additionally, gene expression divergences for olfactory receptor genes were investigated during embryonic development stages of common carp. We aim to determine the abundance of common carp olfactory receptor genes, explore the evolutionary fate and expression dynamics, and provide some genomic clues for the evolution of polyploid olfactory after whole-genome duplication and for future studies of teleost olfactory.
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http://dx.doi.org/10.1016/j.gene.2021.145468DOI Listing
April 2021

Identification and Expression Analysis of Long Non-coding RNA in Large Yellow Croaker () in Response to Infection.

Front Genet 2020 12;11:590475. Epub 2020 Nov 12.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

Large-scale transcription studies have revealed numerous lncRNAs (long non-coding RNAs). lncRNAs have been proposed to participate in the regulation of a diverse range of biological processes, including transcriptional regulation. Although lncRNAs have attracted increasing attention, the studies in large yellow croaker () are still rare, and they lack systematic analysis. In this study, 101 RNA-seq datasets varied in ages, sexes, and tissues were retrieved from the NCBI database to generate a comprehensive catalog of large yellow croaker transcriptome database. A set of 14,599 high-confidence lncRNAs from 13,673 loci were identified and characterized. Furthermore, RNA-seq datasets obtained from the infection of were employed to investigate the differential expression pattern of lncRNAs and analyze potential biological functions. A total of 77 differentially expressed lncRNAs targeting to 567 protein-coding genes were identified by using expression analysis. Several immune genes, including TLR5, CD2AP, and MMP9, were highlighted. With GO enrichment and KEGG pathway analysis, the immune-related terms or pathways were enriched. This study created a comprehensive dataset of lncRNAs for large yellow croaker, which would be helpful for the researches of functional roles of lncRNAs in large yellow croaker.
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http://dx.doi.org/10.3389/fgene.2020.590475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689269PMC
November 2020

Development and Evaluation of a High-Throughput Single-Nucleotide Polymorphism Array for Large Yellow Croaker ().

Front Genet 2020 23;11:571751. Epub 2020 Oct 23.

Fujian Key Laboratory of Genetics and Breeding of Marine Organisms, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

High-density single-nucleotide polymorphism (SNP) genotyping array is an essential tool for genetic analyses of animals and plants. Large yellow croaker () is one of the most commercially important marine fish species in China. Although plenty of SNPs have been identified in large yellow croaker, no high-throughput genotyping array is available. In this study, a high-throughput SNP array named NingXin-I with 600K SNPs was developed and evaluated. A set of 82 large yellow croakers were collected from different locations of China and re-sequenced. A total of 9.34M SNPs were identified by mapping sequence reads to the large yellow croaker reference genome. About 1.98M candidate SNPs were selected for further analyses by using criteria such as SNP quality score and conversion performance in the final array. Finally, 579.5K SNPs evenly distributed across the large yellow croaker genome with an average spacing of 1.19 kb were proceeded to array production. The performance of NingXin-I array was evaluated in 96 large yellow croaker individuals from five populations, and 83.38% SNPs on the array were polymorphic sites. A further test of the NingXin-I array in five closely related species in Sciaenidae identified 26.68-56.23% polymorphic SNP rate across species. A phylogenetic tree inferred by using the genotype data generated by NingXin-I confirmed the phylogenetic distance of the species in Sciaenidae. The performance of NingXin-I in large yellow croaker and the other species in Sciaenidae suggested high accuracy and broad application. The NingXin-I array should be valuable for quantitative genetic studies, such as genome-wide association studies (GWASs), high-density linkage map construction, haplotype analysis, and genome-based selection.
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http://dx.doi.org/10.3389/fgene.2020.571751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645154PMC
October 2020

Transarterial chemoembolization combined with microwave ablation versus microwave ablation only for Barcelona clinic liver cancer Stage B hepatocellular carcinoma: A propensity score matching study.

J Cancer Res Ther 2020 Sep;16(5):1027-1037

Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China.

Purpose: We aimed to compare the outcomes of microwave ablation (MWA) alone with those of transarterial chemoembolization combined with MWA (TACE-MWA) for Barcelona clinic liver cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and to identify the prognostic factors associated with the two treatments.

Materials And Methods: This retrospective study was conducted in 150 BCLC Stage B HCC patients from April 2006 to November 2017. Of these, 88 patients were treated with MWA alone while 62 with TACE-MWA. Propensity score matching (PSM) was conducted to adjust for imbalances in clinical parameters. Procedure-related complications, local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) were analyzed.

Results: Before PSM, the maximal tumor diameters were 6.0 ± 1.0 cm and 6.7 ± 1.3 cm in the TACE-MWA and MWA groups, respectively, with a significant difference (P = 0.002); a significant difference was also detected in α-fetoprotein level (P = 0.013). After PSM, no difference was found in the two parameters (P = 0.067, 0.470). Before and after PSM, no difference was detected in the procedure-related complications (P = 0.803 vs. 1.000, P = 1.000 vs. 1.000), RFS (P = 0.786 vs. 0.689), and OS (P = 0.684 vs. 0.929). Tumor size and α-fetoprotein level were independent influencing factors for OS before and after PSM (P = 0.009, 0.023), while tumor size (D > 7) was an independent risk factor for poor OS (P = 0.011). Tumor number was an independent risk factor for RFS before and after PSM (P = 0.007 vs. P = 0.008). A significant difference was detected in LTP between the two groups with single tumor before and after PSM (P = 0.059 vs. P = 0.006).

Conclusions: The MWA alone group had RFS and OS comparable to that of the TACE-MWA group. TACE-MWA was effective in controlling LTP in patients with a single tumor.
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http://dx.doi.org/10.4103/jcrt.JCRT_380_19DOI Listing
September 2020

Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer.

Sci Rep 2020 08 12;10(1):13619. Epub 2020 Aug 12.

College of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, 180 WuSi Road, Lianchi District, Baoding, 071002, China.

Troxipide is widely used to treat gastric ulcer (GU) in the clinic. However, a lack of systematic metabolic, pharmacokinetic and pharmacological studies limits its clinical use. This study aimed to firstly explore the metabolic, pharmacokinetic and pharmacological mechanisms of troxipide in rats with GU compared to normal control (NC) rats. First, metabolic study was perormed by a highly selective, high-resolution mass spectrometry method. A total of 45 metabolites, including 9 phase I metabolites and 36 phase II metabolites, were identified based on MS/MS spectra. Subsequently, the pharmacokinetics results suggested that the C, K, t, AUC and AUC of troxipide were significantly increased in rats with GU compared with NC rats. The V, K and absolute bioavailability of troxipide were obviously decreased in rats with GU compared with NC rats, and its tissue distribution (in the liver, lung and kidney) was significantly different between the two groups of rats. Additionally, the pharmacodynamic results suggested that the levels of biochemical factors (IL-17, IL-6, TNF-α, IFN-γ, AP-1, MTL, GAS, and PG-II) were significantly increased, the PG-Ӏ level was obviously decreased, and the protein expression levels of HSP-90, C-Cas-3 and C-PARP-1 were markedly increased in rats with GU compared with NC rats. The above results suggested that the therapeutic mechanisms underlying the metabolic, pharmacokinetic and pharmacological properties of troxipide in vivo in rats deserve further attention based on the importance of troxipide in the treatment of GU in this study, and these mechanisms could be targets for future studies.
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http://dx.doi.org/10.1038/s41598-020-70312-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423950PMC
August 2020

Rhodium-catalyzed ortho-acrylation of aryl ketone O-methyl oximes with cyclopropenones.

Org Biomol Chem 2020 05;18(20):3823-3826

State Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou, Gansu, China.

An efficient Rh-catalyzed ortho-acrylation reaction for the synthesis of chalcones from O-methyl ketoximes and cyclopropenones via C-H bond activation has been described. This cross-coupling reaction exhibits high functional group tolerance and regioselectivity. A wide range of chalcone derivatives are obtained in moderate to good yields under mild conditions.
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http://dx.doi.org/10.1039/d0ob00064gDOI Listing
May 2020

Fine-Scale Population Genetic Structure and Parapatric Cryptic Species of Kuruma Shrimp (), Along the Northwestern Pacific Coast of China.

Front Genet 2020 25;11:118. Epub 2020 Feb 25.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

The kuruma shrimp () includes two cryptic species, which are distributed mostly allopatrically but co-occur in the northern South China Sea (from Huilai to Beihai). To obtain a better understanding of the fine-scale genetic structure and parapatric diversification of these two varieties in the northwestern Pacific region, we used a genotyping-by-sequencing (GBS) and comparative transcriptomics approach to establish their phylogenetic relationships. Using the GBS technique, we genotyped 28891 SNPs in 160 individuals in the Northwest Pacific. The results supported two highly diverged evolutionary lineages of kuruma shrimp (var. I and II). The ND and XM populations showed complex genetic patterns, which might be affected by the complex environment of the Taiwan Strait. In addition, the migration rates and inbreeding coefficients of XM and BH were much lower than those of the other populations, which might be related to the land-sea changes and complex ocean currents in the Taiwan Strait and Qiongzhou Strait. Based on the synonymous substitution rates () of 2,491 candidate orthologs, we estimated that the divergence time between the two varieties was 0.26~0.69 Mya. Choice and no-choice interbreeding experiments provided support for the biological species concept, by showing the existence of reproductive isolation or incompatibility. In view of these differences between the two species, we believe that it is essential and urgent to establish a genetic database for each and reevaluate their ecological suitable conditions in order to improve species-specific culturing techniques. Moreover, this research can serve as a case study for future research on speciation and hybridization.
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http://dx.doi.org/10.3389/fgene.2020.00118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052491PMC
February 2020

Transcriptome analysis reveals the temporal gene expression patterns in skin of large yellow croaker (Larimichthys crocea) in response to Cryptocaryon irritans infection.

Fish Shellfish Immunol 2020 Apr 16;99:462-472. Epub 2020 Feb 16.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361102, China; State Key Laboratory of Large Yellow Croaker Breeding, Ningde Fufa Fisheries Company Limited, Ningde, 352130, China; Fujian Key Laboratory of Genetics and Breeding of Marine Organisms, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361102, China. Electronic address:

Large yellow croaker (Larimichthys crocea) is one of the most important mariculture fish in China. In the past decades, cryptocaryonosis caused by Cryptocryon irritans has led to huge economic losses, posing great threat to the healthy and sustainable development of L. crocea mariculture industry. As the largest immunologically active mucosal organ in fish, skin provides the first defense line against external pathogens. To better understand the gene expression dynamics, the large yellow croakers were artificially infected with C. irritans and their skin tissues were collected at 0 h, 24 h, 48 h, 72 h and 96 h post infection. The total RNA in the skin tissues were extracted and the transcriptome were sequenced. After sequencing, a total of 1,131, 311, 140 million high quality RNA-seq reads were collected. A set of 215, 473, 968, 1055 differentially expressed genes were identified at 24 h, 48 h, 72 h and 96 h post infection respectively. Further analysis clustered these DEGs into six profiles and 75 hub genes for six profiles were identified. Among these hub genes, 18 immune related genes including TLR5, TOPK, NFKBIZ, MAPK14A were identified post C. irritans infection. Cytokine-cytokine receptor interaction was the only pathway that significantly enriched at four timepoints post infection. This study provides an in-depth understanding of skin transcriptome variance of large yellow croaker after C. irritans infection, which would be helpful for further understanding of the molecular mechanism of L. crocea in response to C. irritans infection.
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http://dx.doi.org/10.1016/j.fsi.2020.02.024DOI Listing
April 2020

Mitogenomic Perspectives on the Adaptation to Extreme Alkaline Environment of Amur ide (Leuciscus waleckii).

Mar Biotechnol (NY) 2020 Apr 6;22(2):220-232. Epub 2020 Feb 6.

College of Fishery Henan Normal University, Xinxiang, 453007, Henan, China.

Amur ide (Leuciscus waleckii, Family Cyprinidae) is widely distributed in Northeast Asia. L. waleckii usually inhabits freshwater environments but can also survive in the Lake Dali Nur, one of the most extreme aquatic environments on the earth, with an alkalinity up to 50 mmol/L (pH 9.6). To investigate mechanisms of mitogenomic evolution underlying adaptation to extreme environments, we determined 30 complete mitogenomes that included Lake Dali Nur (alkaline environment, AL) population and Amur basin (freshwater environment, FW) population. Through phylogenetic and divergence time analysis, we found that AL and FW populations forming distinct two groups which were consistent with geographic divergence (the formation of Lake Dali Nur). In addition, we found that almost of the windows exhibited higher nucleotide diversity in FW population (avg 0.0046) than AL population (avg 0.0012). This result indicated that severe environment selection had remarkably reduced the genetic diversity of mitogenome in AL population and suggested that severe environment selection had remarkably reduced the genetic diversity of mitogenome in the AL population. Compared with the FW population (ω = 0.064), the AL population (ω = 0.092) had a larger mean ω (dN/dS ratios) value for the 13 concatenated mitochondrial protein-coding genes, indicating that the high alkaline tolerated group had accumulated more nonsynonymous mutations. These nonsynonymous mutations had resulted in slightly beneficial amino acid changes that allowed adaption to the severe conditions. This study provides an additional view to decipher the adaptive mitogenome evolution of L. waleckii of the high alkaline environment.
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http://dx.doi.org/10.1007/s10126-020-09946-7DOI Listing
April 2020

Construction of a High-Density Genetic Linkage Map and QTL Mapping for Growth-Related Traits in Takifugu bimaculatus.

Mar Biotechnol (NY) 2020 Feb 3;22(1):130-144. Epub 2020 Jan 3.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

Takifugu bimaculatus is a euryhaline species, distributed ranging from the southern Yellow Sea to the South China Sea. Their tolerance to a wide range of salinity and temperature, coupled with a desirable firm texture, makes T. bimaculatus a strong candidate for Takifugu aquaculture in subtropics areas. Due to the increasing demand in markets and emerging of the Takifugu aquaculture industry, close attention has been paid to improvement on the T. bimaculatus production. In aquaculture, the great effort has been put into marker-assisted selective breeding, and efficient improvement was realized. However, few genetic resources on T. bimaculatus are provided so far. Aiming at understanding the genetic basis underlying important economic growth traits, facilitating genetic improvement and enriching the genetic resource in T. bimaculatus, we constructed the first genetic linkage map for T. bimaculatus via double digestion restriction-site association DNA sequencing and conducted quantitative traits locus (QTL) mapping for growth-related traits. The map comprised 1976 single nucleotide polymorphism markers distributed on 22 linkage groups (LG), with a total genetic distance of 2039.74 cM. Based on the linkage map, a chromosome-level assembly was constructed whereby we carried out comparative genomics analysis, verifying the high accuracy on contigs ordering of the linkage map. On the other hand, 18 QTLs associated with growth traits were detected on LG6, LG7, LG8, LG10, LG20, and LG21 with phenotypical variance ranging from 15.1 to 56.4%. Candidate genes participating in cartilage development, fat accumulation, and other growth-related regulation activities were identified from these QTLs, including col11a1, foxa2, and thrap3. The linkage map provided a solid foundation for chromosomes assembly and refinement. QTLs reported here unraveled the genomic architecture of some growth traits, which will advance the investigation of aquaculture breeding efforts in T. bimaculatus.
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http://dx.doi.org/10.1007/s10126-019-09938-2DOI Listing
February 2020

The allotetraploid origin and asymmetrical genome evolution of the common carp Cyprinus carpio.

Nat Commun 2019 10 11;10(1):4625. Epub 2019 Oct 11.

Heilongjiang River Fishery Research Institute, Chinese Academy of Fishery Sciences, Harbin, 150001, China.

Common carp (Cyprinus carpio) is an allotetraploid species derived from recent whole genome duplication and provides a model to study polyploid genome evolution in vertebrates. Here, we generate three chromosome-level reference genomes of C. carpio and compare to related diploid Cyprinid genomes. We identify a Barbinae lineage as potential diploid progenitor of C. carpio and then divide the allotetraploid genome into two subgenomes marked by a distinct genome similarity to the diploid progenitor. We estimate that the two diploid progenitors diverged around 23 Mya and merged around 12.4 Mya based on the divergence rates of homoeologous genes and transposable elements in two subgenomes. No extensive gene losses are observed in either subgenome. Instead, we find gene expression bias across surveyed tissues such that subgenome B is more dominant in homoeologous expression. CG methylation in promoter regions may play an important role in altering gene expression in allotetraploid C. carpio.
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http://dx.doi.org/10.1038/s41467-019-12644-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789147PMC
October 2019

The sequencing and de novo assembly of the Larimichthys crocea genome using PacBio and Hi-C technologies.

Sci Data 2019 10 1;6(1):188. Epub 2019 Oct 1.

State Key Laboratory of Large Yellow Croaker Breeding, Ningde Fufa Fisheries Company Limited, Ningde, 352130, China.

Larimichthys crocea is an endemic marine fish in East Asia that belongs to Sciaenidae in Perciformes. L. crocea has now been recognized as an "iconic" marine fish species in China because not only is it a popular food fish in China, it is a representative victim of overfishing and still provides high value fish products supported by the modern large-scale mariculture industry. Here, we report a chromosome-level reference genome of L. crocea generated by employing the PacBio single molecule sequencing technique (SMRT) and high-throughput chromosome conformation capture (Hi-C) technologies. The genome sequences were assembled into 1,591 contigs with a total length of 723.86 Mb and a contig N50 length of 2.83 Mb. After chromosome-level scaffolding, 24 scaffolds were constructed with a total length of 668.67 Mb (92.48% of the total length). Genome annotation identified 23,657 protein-coding genes and 7262 ncRNAs. This highly accurate, chromosome-level reference genome of L. crocea provides an essential genome resource to support the development of genome-scale selective breeding and restocking strategies of L. crocea.
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http://dx.doi.org/10.1038/s41597-019-0194-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773841PMC
October 2019

The sequence and de novo assembly of Takifugu bimaculatus genome using PacBio and Hi-C technologies.

Sci Data 2019 09 30;6(1):187. Epub 2019 Sep 30.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361102, China.

Takifugu bimaculatus is a native teleost species of the southeast coast of China where it has been cultivated as an important edible fish in the last decade. Genetic breeding programs, which have been recently initiated for improving the aquaculture performance of T. bimaculatus, urgently require a high-quality reference genome to facilitate genome selection and related genetic studies. To address this need, we produced a chromosome-level reference genome of T. bimaculatus using the PacBio single molecule sequencing technique (SMRT) and High-through chromosome conformation capture (Hi-C) technologies. The genome was assembled into 2,193 contigs with a total length of 404.21 Mb and a contig N50 length of 1.31 Mb. After chromosome-level scaffolding, 22 chromosomes with a total length of 371.68 Mb were constructed. Moreover, a total of 21,117 protein-coding genes and 3,471 ncRNAs were annotated in the reference genome. The highly accurate, chromosome-level reference genome of T. bimaculatus provides an essential genome resource for not only the genome-scale selective breeding of T. bimaculatus but also the exploration of the evolutionary basis of the speciation and local adaptation of the Takifugu genus.
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http://dx.doi.org/10.1038/s41597-019-0195-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768875PMC
September 2019

Crystal Structure of Refolding Fusion Core of Lassa Virus GP2 and Design of Lassa Virus Fusion Inhibitors.

Front Microbiol 2019 13;10:1829. Epub 2019 Aug 13.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

The envelope glycoproteins GP1 and GP2 of Lassa virus (LASV) bind to the host cell receptors to mediate viral infection. So far, no approved vaccines and specific treatment options against LASV exist. To develop specific fusion inhibitors against LASV, we solved the crystal structure of the post-fusion 6 helix bundle (6-HB) formed by two heptad repeat domains (HR1 and HR2) of GP2. This fusion core contains a parallel trimeric coiled-coil of three HR1 helices, around which three HR2 helices are entwined in an antiparallel manner. Various hydrophobic and charged interactions form between HR1 and HR2 domains to stabilize the overall conformation of GP2 fusion core. Based on the structure, we designed several peptides spanning the HR2 domain and tested their antiviral activities. We found that the longer HR2 peptides were effective in inhibiting LASV GPC protein-mediated cell-cell fusion under low pH condition. These results not only suggest that LASV infects the target cell mainly through endocytosis, including micropinocytosis, and membrane fusion at low pH, but also provide an important basis for rational design of LASV fusion inhibitors.
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http://dx.doi.org/10.3389/fmicb.2019.01829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700223PMC
August 2019

Patterns of Geographical and Potential Adaptive Divergence in the Genome of the Common Carp ().

Front Genet 2019 12;10:660. Epub 2019 Jul 12.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

The common carp, , is a cyprinid fish species cultured in Europe and Asia. It accounts for >70% of freshwater aquaculture production worldwide. We conducted a population genomics analysis on using high-throughput SNP genotyping of 2,198 individuals from 14 populations worldwide to determine the genetic architecture of common carp populations and the genetic bases for environmental adaptation. Structure analyses including phylogeny and principal component analysis were also conducted, showing distinct geographical patterns in European and Asian populations. The linkage disequilibrium block average lengths of the 14 populations ranged from 3.94 kb to 36.67 kb. Genes within selective sweep regions were identified by genome scanning among the different populations, including , , and . Gene Ontology and KEGG enrichment analyses revealed potential trait-related loci and genes associated with body shape, scaling patterns, and skin color. This population genomics analysis may provide valuable clues for future genome-assisted breeding of .
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http://dx.doi.org/10.3389/fgene.2019.00660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640160PMC
July 2019

Structure of the full-length Clostridium difficile toxin B.

Nat Struct Mol Biol 2019 08 15;26(8):712-719. Epub 2019 Jul 15.

Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.

Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB. Here, we report a 3.87-Å-resolution crystal structure of TcdB holotoxin that captures a unique conformation of TcdB at endosomal pH. Complementary biophysical studies suggest that the C-terminal combined repetitive oligopeptides (CROPs) domain of TcdB is dynamic and can sample open and closed conformations that may facilitate modulation of TcdB activity in response to environmental and cellular cues during intoxication. Furthermore, we report three crystal structures of TcdB-antibody complexes that reveal how antibodies could specifically inhibit the activities of individual TcdB domains. Our studies provide novel insight into the structure and function of TcdB holotoxin and identify intrinsic vulnerabilities that could be exploited to develop new therapeutics and vaccines for the treatment of CDI.
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http://dx.doi.org/10.1038/s41594-019-0268-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684407PMC
August 2019

Identification and Characterization of the Two-Component System HK8700-RR8701 of Kocuria rhizophila DC2201.

Protein J 2019 12;38(6):683-692

College of Life Science, Jiangxi Normal University, Nanchang, 330022, People's Republic of China.

Two-component systems (TCSs) are highly conserved in prokaryotes, endowing cells with multiple physiological functions to respond to changes in the ambient environment. The signaling pathway of a typical TCS consists of a sensory histidine kinase and a response regulator. The TCSs of Kocuria rhizophila, which is usually used as a target strain for various antibiotics and other adverse factors, have captured our interest due to their potential roles in bacterial adaptation for survival. Herein, the distribution and putative biological functions of the TCSs of K. rhizophila DC2201 were analyzed by using bioinformatics, and a preliminary TCS regulatory network was constructed. A representative and important TCS (i.e., HK8700-RR8701 system), which is homologous to the LiaS-LiaR system previously discovered in Bacillus subtilis, was identified and characterized through yeast two-hybrid screening and phosphorylation assays. Detailed information of TCSs is expected to offer novel insights into the adaptation mechanism of K. rhizophila and thus boost its application.
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http://dx.doi.org/10.1007/s10930-019-09853-4DOI Listing
December 2019

Chromosome-Level Assembly of the Chinese Seabass () Genome.

Front Genet 2019 4;10:275. Epub 2019 Apr 4.

Shenzhen Research Institute of Xiamen University, Shenzhen, China.

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http://dx.doi.org/10.3389/fgene.2019.00275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459032PMC
April 2019

An examination of the Northern Hemisphere mid-latitude storm track interannual variability simulated by climate models-sensitivity to model resolution and coupling.

Clim Dyn 2019 4;52(7):4247-4268. Epub 2018 Aug 4.

5Department of Mathematics and Statistics, Texas A&M University-Corpus Christi, Corpus Christi, TX 78412 USA.

The model fidelity in simulating the Northern Hemisphere storm track interannual variability and the connections of this variability to the low frequency atmospheric variations and oceanic variations are examined based on the atmospheric European Centre for Medium-Range Weather Forecasts (ECMWF) model and coupled NCAR Community Climate System Model (CCSM) systems at different horizontal resolutions. The atmospheric general circulation model (AGCM) runs are forced by observed sea surface temperatures (SST) with varying atmospheric resolutions, while the coupled general circulation model (CGCM) runs have a fixed atmospheric resolution but varying oceanic resolutions. The phases, between the North Pacific (NP) and North Atlantic (NA) sectors, of the simulated hemisphere-scale Empirical Orthogonal Function (EOF) modes of the storm track fluctuations change with the model resolution, suggesting the storm track variability in NP and NA basins are largely independent. The models can qualitatively reproduce the basin-scale EOFs of both NP and NA storm track variability. These EOFs are not sensitive to either atmospheric or oceanic model horizontal resolutions, but their magnitudes from the CGCM runs are substantially underestimated. The storm track variations over NP basin are hybrid of internal atmospheric variations and external forcing from the underlying conditions, but the fluctuations over the NA basin are merely atmospheric internal variability. The NP storm track variability from SST forcing accounts for 4.4% of the total variance in observations, while it only has less than 2% of the total in all AGCM simulations. The external forcing to the storm track variations is more realistically reproduced in the higher atmospheric resolution runs. The air-sea coupling makes the SST feedbacks to the atmospheric internal variability, absent in the atmospheric ECMWF model hindcasts, emerge in the coupled CCSM simulations.
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http://dx.doi.org/10.1007/s00382-018-4378-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445401PMC
August 2018

Precipitation characteristic changes due to global warming in a high-resolution (16 km) ECMWF simulation.

Q J R Meteorol Soc 2019 Jan 9;145(718):303-317. Epub 2019 Jan 9.

Department of Mathematics and Statistics Texas A&M University-Corpus Christi Corpus Christi Texas.

Changes in precipitation amount, intensity and frequency in response to global warming are examined using global high-resolution (16 km) climate model simulations based on the European Centre for Medium-range Weather Forecasts (ECMWF) Integrated Forecast System (IFS) conducted under Project Athena. Our study shows the increases of zonal-mean total precipitation in all latitudes except the northern subtropics (15°-30°N) and southern subtropics-to-midlatitudes (30°-40°S). The probability distribution function (PDF) changes in different latitudes suggest a higher occurrence of light precipitation (LP; ≤1 mm/day) and heavy precipitation (HP; ≥30 mm/day) at the expense of moderate precipitation reduction (MP; 1-30 mm/day) from Tropics to midlatitudes, but an increase in all categories of precipitation in polar regions. On the other hand, the PDF change with global warming in different precipitation climatological zones presents another image. For all regions and seasons examined, there is an HP increase at the cost of MP, but LP varies. The reduced MP in richer precipitation zones resides in the PDF peak intensities, which linearly increase with the precipitation climatology zones. In particular in the Tropics (20°S to 20°N), the precipitation PDF has a flatter distribution (i.e. HP and LP increases with MP reduction) except for the Sahara Desert. In the primary precipitation zones in the subtropics (20°-40°) of both hemispheres, precipitation over land switches toward higher intensity (HP increases, but MP and LP decrease) in both winter and summer, while precipitation over ocean in both seasons shows a flattening trend in the intensity distribution. For the major precipitation zones of the mid-to-high latitude belt (40°-70°), PDF of precipitation tends to be flatter over ocean in summer, but switches toward higher intensities over land in both summer and winter, as well as over ocean in winter.
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http://dx.doi.org/10.1002/qj.3432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472574PMC
January 2019

Transcriptional differences provide insight into environmental acclimatization in wild amur ide (Leuciscus waleckii) during spawning migration from alkalized lake to freshwater river.

Genomics 2019 05 13;111(3):267-276. Epub 2018 Nov 13.

Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen University, Xiamen 361102, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; State Key Laboratory of Large Yellow Croaker Breeding, Ningde Fufa Fisheries Company Limited, Ningde 352103, China. Electronic address:

Amur ide (Leuciscus waleckii) inhabits alkaline water in Lake Dali Nur and migrates to fresh water river for spawning every year. To investigate the potential genetic mechanisms underlying their alkaline acclimation, adaptation, and spawning migration, we performed differential gene expression analysis using high-throughput RNA-Seq data from liver of Amur ide samples collected before and after spawning migration. First, the short RNA-Seq reads were de novo assembled into 44,318 contigs, and provided the transcriptome reference sequences. Differential gene expression analysis identified 2575 genes with significant differential expression (p-value ≤.01, log2-fold-change ≥2). GO enrichment and KEGG pathway analyses were subsequently performed to determine gene functions and regulation. The results indicated that there were numerous differentially expressed genes involved in acid-base regulation, nitrogenous waste excretion, sexual maturation and reproduction, and stress response. These results provide fundamental information for further analyses of the physiological and molecular mechanisms underlying Amur ide alkaline acclimation, adaptation, and spawning migration.
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http://dx.doi.org/10.1016/j.ygeno.2018.11.007DOI Listing
May 2019

Genetic Mapping of Head Size Related Traits in Common Carp ().

Front Genet 2018 9;9:448. Epub 2018 Oct 9.

State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, China.

Head size is important economic trait for many aquaculture fish which is directly linked to their carcass yield. The genetic basis of head size trait remains unclear in many widely cultured fish species. Common carp () is one of the most widely studied fish due to its importance on both economic and environmental aspects. In this study, we performed genome-wide association study using 433 Yellow River carp individuals from multiple families to identify loci and genes potentially associated with head size related traits including head length (HL), head length/body length ratio (HBR), eye diameter (ED), and eye cross (EC). QTL mapping was utilized to filter the effects of population stratification and improve power for the candidates identification in the largest surveyed family with a published genetic linkage map. Twelve SNPs showed significant for head size traits in GWAS and 18 QTLs were identified in QTL mapping. Our study combining both GWAS and QTL mapping could compensate the deficiency from each other and advance our understanding of head size traits in common carp. To acquire a better understanding of the correlation between head size and body growth, we also performed comparisons between QTLs of head size traits and growth-related traits. Candidate genes underlying head size traits were identified surrounding the significant SNPs, including , , , , , , , , Many of these genes have been identified with potential functions on bone formation and growth. was a putative gene associated with both head size and body growth in Yellow River carp. The teleost-specific was a candidate head size related gene, related to both HL and HBR. Our study also indicated the importance of Igf signaling pathway for both growth and head size determination in common carp, which could be potentially used in future selective breeding in common carp as well as other species.
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http://dx.doi.org/10.3389/fgene.2018.00448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190898PMC
October 2018

Genome-Scale Association Study of Abnormal Scale Pattern in Yellow River Carp Identified Previously Known Causative Gene in European Mirror Carp.

Mar Biotechnol (NY) 2018 Oct 7;20(5):573-583. Epub 2018 Jun 7.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361102, China.

Common carp (Cyprinus carpio) is one of the most widely studied fish species due to its great economic value and strong environmental adaptability. Scattered scale, a typical phenotype of the mirror carp that is derived from Europe, has never been observed in the Yellow River carp previously. We recently identified approximately one fourth of the F1 progenies displaying scattered scale in a full-sib Yellow River carp family in our breeding program, despite both parents that showed wild type with normal scale patterns. This family provides us unique materials to investigate the genetic basis underlying the abnormal scale mutant in Yellow River carp population. Genome-wide association study (GWAS) and association mapping were performed based on genome-wide single nucleotide polymorphisms (SNP) genotyped with common carp 250 K SNP genotyping array in 82 samples of the Yellow River carp family. We identified a 1.4 Mb genome region that was significantly associated with abnormal scattered scale patterns. We further identified a deletion mutation in fibroblast growth factor receptor 1 a1 (fgfr1a1) gene within this genome region. Amplification and sequencing analysis of this gene revealed a 311-bp deletion in intron 10 and exon 11, which proved that fgfr1a1 could be the causal gene responsible for abnormal scattered scale in the Yellow River carp family. Since similar fragment mutation with 306-bp and 310-bp deletions had been previously reported as causal mutation of scattered scale patterns in the mirror carp, we speculate that either the deletion mutation was introduced from Europe-derived mirror carp or the deletion independently occurred in the mutation hotspot in fgfr1a1 gene. The results provided insights into the genetic basis of scale pattern mutant in Yellow River carp population, which would help us to eliminate the recessive allele of the abnormal scale patterns in Yellow River carp population by molecular marker-assisted breeding.
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http://dx.doi.org/10.1007/s10126-018-9827-3DOI Listing
October 2018

Structure of the DNA-binding domain of human myelin-gene regulatory factor reveals its potential protein-DNA recognition mode.

J Struct Biol 2018 08 2;203(2):170-178. Epub 2018 May 2.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China; National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China. Electronic address:

Myelin-gene regulatory factor (MYRF) is a membrane-bound transcription factors, which is responsible for the differentiation of oligodendrocytes and myelination of central nervous system. Followed by a self-cleavage by the intramolecular chaperone auto-processing (ICA) domain, DNA-binding domain (DBD) of MYRF is released from the endoplasmic reticulum (ER) and was then translocated to the nucleus to regulate gene expression. In present work, we have solved the crystal structure of the human MYRF-DBD to 1.85-Å resolution. It exhibits a typical s-type Ig-fold and packs as symmetric trimeric form in the crystal via hydrogen-bond networks in three regions. Accordingly, we identified a couple of key residues on MYRF-DBD, which might play important roles in DNA-binding, in particular Arg521 on its C-terminal tail. The R521A mutant of DBD showed only 17% affinity to dsDNA targets compared to wild-type DBD. Then we built a plausible protein-DNA binding model of MYRF-DBD, which will help to elucidate its mechanism in DNA-binding and transcriptional regulation.
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http://dx.doi.org/10.1016/j.jsb.2018.04.007DOI Listing
August 2018

Metal-free iodine(iii)-promoted synthesis of 2,5-diaryloxazoles.

Org Biomol Chem 2018 05;16(17):3104-3108

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.

A nonmetal-catalyzed oxidative cyclization to achieve 2,5-disubstituted oxazoles from inexpensive and readily available substituted chalcone, (diacetoxyiodo)benzene (PIDA) and ammonium acetate (NH4OAc) at room temperature is described. The reaction forms a variety of 2,5-diaryloxazoles in good to excellent yields with broad substrate scope under mild conditions without the requirement of ligands and additional bases.
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http://dx.doi.org/10.1039/c8ob00401cDOI Listing
May 2018

Effect of curcumin on vascular endothelial growth factor in hypoxic HepG2 cells via the insulin-like growth factor 1 receptor signaling pathway.

Exp Ther Med 2018 Mar 22;15(3):2922-2928. Epub 2018 Jan 22.

Department of General Surgery, The 175th Hospital of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China.

To investigate the anti-angiogenic effect and underlying molecular mechanisms of curcumin on HepG2 cells under hypoxic conditions, insulin-like growth factor 1 receptor (IGF-1R) knockout HepG2 cells were constructed using a clustered regularly interspaced short palindromic repeats/Cas9 genome-editing system. Hypoxic conditions were generated using cobalt chloride (CoCl). An MTT assay was performed to measure the effects of curcumin on cell viability in hypoxia-induced IGF-1R knockout HepG2 cells, while western blot analysis was used to detect the expression of IGF-1R, phosphorylated (p)-protein kinase B (Akt), p-extracellular signal-regulated kinases (Erk)1/2, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). The results revealed that CoCl at low concentrations (50 and 100 µM) had no significant inhibitory effects on IGF-1R knockout HepG2 cells. However, with increasing concentrations of CoCl and treatment time, cell viability decreased and was significantly reduced at 150, 200 and 400 µM compared with the control group (P<0.05). The expression of HIF-1α and VEGF were significantly increased when the cells were treated with 150 or 200 µM CoCl compared with the control (P<0.05). With the increase of CoCl concentration or the treatment time, the expression of HIF-1α and VEGF were upregulated gradually. Additionally, curcumin significantly inhibited the expression of p-Akt, p-Erk1/2, HIF-1α and VEGF in hypoxia-induced IGF-1R knockout HepG2 cells. In conclusion, the findings of the present study suggest that curcumin may serve a pivotal role in tumor suppression via the inhibition of IGF-1R-mediated angiogenesis under hypoxic conditions.
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http://dx.doi.org/10.3892/etm.2018.5783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867490PMC
March 2018

Population Genomics Reveals Genetic Divergence and Adaptive Differentiation of Chinese Sea Bass (Lateolabrax maculatus).

Mar Biotechnol (NY) 2018 Feb 18;20(1):45-59. Epub 2017 Dec 18.

Fujian Collaborative Innovation Centre for Exploitation and Utilization of Marine Biological Resources, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361005, China.

The marine species usually show high dispersal capabilities accompanied by high levels of gene flow. On the other hand, many physical barriers distribute along the continental marginal seas and may prevent dispersals and increase population divergence. These complexities along the continental margin generate serious challenges to population genetic studies of marine species. Chinese sea bass Lateolabrax maculatus distributes broad latitudinal gradient spanning from the tropical to the mid-temperate zones in the continental margin seas of the Northwest Pacific Ocean. Using the double digest restriction-site-associated DNA tag sequencing (ddRAD) approach, we genotyped 10,297 SNPs for 219 Chinese seabass individuals of 12 populations along the Chinese coast in the Northwest Pacific region. Genetic divergence among these populations was evaluated, and population structure was established. The results suggested that geographically distant populations in the Bohai Gulf and the Beibu Gulf retain significant genetic divergence, which are connected by a series of intermediate populations in between. The results also suggested that Leizhou Peninsula, Hainan Island, and Shandong Peninsula are major physical barriers and substantially block gene flow and genetic admixture of L. maculatus. We also investigated the potential genetic basis of local adaptation correlating with population differentiation of L. maculatus. The sea surface temperature is a significantly differentiated environmental factor for the distribution of L. maculatus. The correlation of water temperature and genetic variations in extensively distributed populations was investigated with Bayesian-based approaches. The candidate genes underlying the local selection in geographically divergent populations were identified and annotated, providing clues to understand the potential mechanisms of adaptive evolution. Overall, our genome scale population genetic analysis provided insight into population divergence and local adaptation of Chinese sea bass in the continental marginal seas along Chinese coast.
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http://dx.doi.org/10.1007/s10126-017-9786-0DOI Listing
February 2018

Copper-Catalyzed Tandem Aerobic Oxidative Cyclization for the Synthesis of Polysubstituted Quinolines via C(sp)/C(sp)-H Bond Functionalization.

J Org Chem 2017 10 28;82(19):10110-10120. Epub 2017 Sep 28.

State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University , Lanzhou, Gansu 730000, China.

One-pot Cu-catalyzed tandem aerobic oxidative cyclization for the synthesis of quinolines from 2-vinylanilines/2-arylanilines and 2-methylquinolines via C(sp)-H/C(sp)-H bond functionalization has been developed. Dioxygen as an ideal oxidant has been employed for this transformation. The substrates bearing various functional groups perform well in this process and generate the desired products in moderate to good yields.
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http://dx.doi.org/10.1021/acs.joc.7b01575DOI Listing
October 2017

Synthesis of 2,3-Disubstituted NH Indoles via Rhodium(III)-Catalyzed C-H Activation of Arylnitrones and Coupling with Diazo Compounds.

J Org Chem 2017 11 2;82(21):11505-11511. Epub 2017 Oct 2.

State Key Laboratory of Applied Organic Chemistry, Lanzhou University Gansu and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province , Lanzhou 730000, People's Republic of China.

A rhodium-catalyzed intermolecular coupling between arylnitrones and diazo compounds by C-H activation/[4 + 1] annulation with a C(N)-C(acyl) bond cleavage is reported, and 2,3-disubstituted NH indoles are directly synthesized in up to a 94% yield. A variety of functional groups are applicable to this reaction to give the corresponding products with high selectivity. Compared to other previously reported Rh(III)-catalyzed synthesis of homologous series, this method is simpler, more general, and more efficient.
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http://dx.doi.org/10.1021/acs.joc.7b02105DOI Listing
November 2017
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