Publications by authors named "Yuning Chen"

90 Publications

Taping into the super power and magic appeal of ultrasound coupled with EDTA on degradation of 2,4,6-TCP by Fe based advanced oxidation processes.

Chemosphere 2021 Oct 23:132650. Epub 2021 Oct 23.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing, 400045, China.

Chlorophenol is a widely used organic compound, and the environmental and health problems caused by it have being worsened in recent years. This study used 2,4,6-trichlorophenol (2,4,6-TCP) as the target pollutant, and employed ultrasound (US) enhanced zero-valent iron (Fe)/EDTA/air system (FEA), namely US/FEA, to remove 2,4,6-TCP. The influence of single factor experimental conditions such as EDTA concentration, Fe dosage, US power, pH and pollutant concentration on the removal efficiency of 2,4,6-TCP was investigated, and the optimal reaction conditions were determined. The mechanism of reactive oxygen species (ROS) produced by US/FEA was explored. The degradation process and removal mechanism of 2,4,6-TCP in the US/FEA were discussed through the determination and analysis of intermediate products. The results showed that US could continuously activate and renew the Fe surface, accelerate its oxidation and corrosion process, and then continuously and stably produce sufficient amounts of Fe and Fe. Ultrasonic cavitation effect could reduce the difficulty of O activation reaction, and promote the production of sufficient HO. The addition of EDTA made the system have a wide range of pH applications, and its performance under neutral and alkaline conditions was also superior. The ROS of US/FEA included ·OH, O and Fe(IV), where Fe(IV) was the main contributor to the removal of 2,4,6-TCP. In addition, the degradation of 2,4,6-TCP had two processes including dechlorination and benzene ring opening. First, 2,4,6-TCP was dechlorinated and degraded into phenol. And then, phenol was degraded into small molecular acids by ring-opening, and finally it was mineralized into CO and HO completely. US/FEA is a promising technology for high-efficiency degradation of organic matter and deep environmental purification.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132650DOI Listing
October 2021

ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.

Signal Transduct Target Ther 2021 08 25;6(1):315. Epub 2021 Aug 25.

Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
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http://dx.doi.org/10.1038/s41392-021-00740-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385704PMC
August 2021

Key Regulators of Sucrose Metabolism Identified through Comprehensive Comparative Transcriptome Analysis in Peanuts.

Int J Mol Sci 2021 Jul 6;22(14). Epub 2021 Jul 6.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan 430062, China.

Sucrose content is a crucial indicator of quality and flavor in peanut seed, and there is a lack of clarity on the molecular basis of sucrose metabolism in peanut seed. In this context, we performed a comprehensive comparative transcriptome study on the samples collected at seven seed development stages between a high-sucrose content variety (ICG 12625) and a low-sucrose content variety (Zhonghua 10). The transcriptome analysis identified a total of 8334 genes exhibiting significantly different abundances between the high- and low-sucrose varieties. We identified 28 differentially expressed genes (DEGs) involved in sucrose metabolism in peanut and 12 of these encoded sugars will eventually be exported transporters (SWEETs). The remaining 16 genes encoded enzymes, such as cell wall invertase (CWIN), vacuolar invertase (VIN), cytoplasmic invertase (CIN), cytosolic fructose-bisphosphate aldolase (FBA), cytosolic fructose-1,6-bisphosphate phosphatase (FBP), sucrose synthase (SUS), cytosolic phosphoglucose isomerase (PGI), hexokinase (HK), and sucrose-phosphate phosphatase (SPP). The weighted gene co-expression network analysis (WGCNA) identified seven genes encoding key enzymes (CIN, FBA, FBP, HK, and SPP), three SWEET genes, and 90 transcription factors (TFs) showing a high correlation with sucrose content. Furthermore, upon validation, six of these genes were successfully verified as exhibiting higher expression in high-sucrose recombinant inbred lines (RILs). Our study suggested the key roles of the high expression of SWEETs and enzymes in sucrose synthesis making the genotype ICG 12625 sucrose-rich. This study also provided insights into the molecular basis of sucrose metabolism during seed development and facilitated exploring key candidate genes and molecular breeding for sucrose content in peanuts.
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http://dx.doi.org/10.3390/ijms22147266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306169PMC
July 2021

Research on a new cationic polyacrylamide (CPAM) with a cationic microblock structure and its enhanced effect on sludge condition and dewatering.

Environ Sci Pollut Res Int 2021 Oct 15;28(37):51865-51878. Epub 2021 May 15.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing, 400045, China.

Flocculation is one of the commonly used sludge conditioning methods in water supply plants, which can improve the sludge dewatering performance by reducing the specific resistance of sludge (SRF), decreasing the amount of sludge, and finally lowering the transportation cost and subsequent disposal cost of sludge. Therefore, it is particularly important to develop new and efficient flocculants. In this paper, the template copolymer of acryloxy trimethylammonium chloride (DAC) and acrylamide (AM) was successfully synthesized by microwave-template copolymerization (MV-TP) using sodium polyacrylate (NaPAA) as template. The template copolymer was analyzed by infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance hydrogen spectroscopy (H NMR), and scanning electron microscopy (SEM). It was found that this template copolymer had obvious cationic microblock structure. In addition, the test results of association constant (K) and polymerization kinetics showed that the MW-TP was assigned to free radical initiated polymerization and the polymerization mechanism was I Zip-up (ZIP). It confirmed the formation of cation fragment structure again. Due to its dense positive charges in this new cationic microblock structure, it greatly improved the functions of electric neutralization, electrical patching, and adsorption bridging. The cationic fragment structure in the template copolymer could help to generate large and dense floc structure and form stable drainage channels. Under external pressure, these large and compact floc structures had greater compressive resistance, which avoided deformation and blockage of drainage channels and voids. It was beneficial to reduce SRF and evidently enhanced sludge dewatering performance.
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http://dx.doi.org/10.1007/s11356-021-14325-3DOI Listing
October 2021

Construction of ddRADseq-Based High-Density Genetic Map and Identification of Quantitative Trait Loci for Trans-resveratrol Content in Peanut Seeds.

Front Plant Sci 2021 18;12:644402. Epub 2021 Mar 18.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, China.

Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural stilbene phytoalexin which is also found to be good for human health. Cultivated peanut ( L.), a worldwide important legume crop, is one of the few sources of human's dietary intake of resveratrol. Although the variations of resveratrol contents among peanut varieties were observed, the variations across environments and its underlying genetic basis were poorly investigated. In this study, the resveratrol content in seeds of a recombination inbred line (RIL) population (Zhonghua 6 × Xuhua 13, 186 progenies) were quantified by high performance liquid chromatography (HPLC) method across four environments. Genotypes, environments and genotype × environment interactions significantly influenced the resveratrol contents in the RIL population. A total of 8,114 high-quality single nucleotide polymorphisms (SNPs) were identified based on double-digest restriction-site-associated DNA sequencing (ddRADseq) reads. These SNPs were clustered into bins using a reference-based method, which facilitated the construction of high-density genetic map (2,183 loci with a total length of 2,063.55 cM) and the discovery of several chromosome translocations. Through composite interval mapping (CIM), nine additive quantitative trait loci (QTL) for resveratrol contents were identified on chromosomes A01, A07, A08, B04, B05, B06, B07, and B10 with 5.07-8.19% phenotypic variations explained (PVE). Putative genes within their confidential intervals might play roles in diverse primary and secondary metabolic processes. These results laid a foundation for the further genetic dissection of resveratrol content as well as the breeding and production of high-resveratrol peanuts.
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http://dx.doi.org/10.3389/fpls.2021.644402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044979PMC
March 2021

Genome sequencing and comparative genomic analysis of highly and weakly aggressive strains of Sclerotium rolfsii, the causal agent of peanut stem rot.

BMC Genomics 2021 Apr 16;22(1):276. Epub 2021 Apr 16.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, P.R. China, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, 430062, China.

Background: Stem rot caused by Sclerotium rolfsii is a very important soil-borne disease of peanut. S. rolfsii is a necrotrophic plant pathogenic fungus with an extensive host range and worldwide distribution. It can infect peanut stems, roots, pegs and pods, leading to varied yield losses. S. rolfsii strains GP3 and ZY collected from peanut in different provinces of China exhibited a significant difference in aggressiveness on peanut plants by artificial inoculation test. In this study, de-novo genome sequencing of these two distinct strains was performed aiming to reveal the genomic basis of difference in aggressiveness.

Results: Scleotium rolfsii strains GP3 and ZY, with weak and high aggressiveness on peanut plants, exhibited similar growth rate and oxalic acid production in laboratory. The genomes of S. rolfsii strains GP3 and ZY were sequenced by Pacbio long read technology and exhibited 70.51 Mb and 70.61 Mb, with contigs of 27 and 23, and encoded 17,097 and 16,743 gene models, respectively. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires, which might be associated with aggressiveness, differed between GP3 and ZY. There were 58 and 45 unique pathogen-host interaction (PHI) genes in GP3 and ZY, respectively. The ZY strain had more carbohydrate-active enzymes (CAZymes) in its secretome than GP3, especially in the glycoside hydrolase family (GH), the carbohydrate esterase family (CBM), and the polysaccharide lyase family (PL). GP3 and ZY also had different effector candidates and putative secondary metabolite synthetic gene clusters. These results indicated that differences in PHI, secreted CAZymes, effectors and secondary metabolites may play important roles in aggressive difference between these two strains.

Conclusions: The data provided a further understanding of the S. rolfsii genome. Genomic comparison provided clues to the difference in aggressiveness of S. rolfsii strains.
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http://dx.doi.org/10.1186/s12864-021-07534-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052761PMC
April 2021

Genome-wide identification of peanut PIF family genes and their potential roles in early pod development.

Gene 2021 May 23;781:145539. Epub 2021 Feb 23.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan 430062, PR China. Electronic address:

Peanut is typically a geocarpic plant. The developing gynophore ('peg') in air could not swell normally until it buries into soil, indicating light-to-dark conversion is necessary for early pod development in peanut. As the subfamily of basic helix-loop-helix (bHLH) transcription factors, phytochrome interacting factors (PIFs) are key regulators involved in light signaling pathways, and play crucial roles in plant growth and development. In the current study, a total of 14 AhPIFs were identified in cultivated peanut genome (Arachis hypogaea L., AABB), while seven AdPIFs and six AiPIFs were discovered in the two wild diploids (A. duranensis (AA), A. ipaensis (BB)) respectively. Phylogenetic analysis revealed that peanut PIFs were clustered into four distinct clades, and members within the same subgroup had conserved motifs and displayed similar exon-intron distribution patterns. Gene synteny analysis indicated most of the PIFs exhibit one-to-one homology relationship between AA and BB subgenome in A. hypogaea, as well as among the three peanut species. Gene duplication detection showed that segmental duplication and purifying selection contributed to the expansion and evolution of peanut PIF gene family. Transcript profiles combined with subcellular localization analysis suggested AhPIF3A4 and AhPIF3B4 may possibly be involved in regulation of peanut early pod development. This study could further facilitate functional characterization of PIFs in peanut and other legumes.
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http://dx.doi.org/10.1016/j.gene.2021.145539DOI Listing
May 2021

A microblock structure type of anionic flocculant for hematite wastewater treatment: template copolymerization mechanism and enhanced flocculation effect.

Environ Sci Pollut Res Int 2021 Jan 29;28(2):1933-1947. Epub 2020 Aug 29.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing, 400045, China.

In this study, a novel anionic template polymer (TPAS) with microblock structure was prepared by ultraviolet light (UV)-assisted template copolymerization (UV-TP). Acrylamide (AM) and sodium styrene sulfonate (SSS) were selected as monomers and polypropylene ammonium chloride (PAAC) was chosen as the template. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), nuclear magnetic resonance hydrogen spectroscopy (H NMR), and thermogravimetry/differential scanning calorimetry (TG/DSC) were used to characterize the polymer chemical structure. The results showed that the attractive anionic microblock structure was formed in TPAS. Besides, the association constant (K) and template reaction kinetics analysis results indicated that the polymerization reaction followed I (ZIP) template copolymerization mechanism. It proved the microblock structure formation again. The anionic microblock structure in TPAM could greatly improve the ability of charge neutralization, electrical patching, and bridging. After the hematite wastewater was conditioned by TPAS with this novel anionic microblock structure, the generated hematite flocs had larger particle size and denser structure. It was favorable for the reduction of turbidity, and the turbidity removal rate could reach 97.8%. TPAS showed excellent flocculation performance for hematite wastewater and had a broad market application prospect.
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http://dx.doi.org/10.1007/s11356-020-10620-7DOI Listing
January 2021

Construction of paclitaxel-based antibody-drug conjugates with a PEGylated linker to achieve superior therapeutic index.

Signal Transduct Target Ther 2020 07 29;5(1):132. Epub 2020 Jul 29.

Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 200126, China.

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http://dx.doi.org/10.1038/s41392-020-00247-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391632PMC
July 2020

In-situ catalytic pyrolysis upgradation of microalgae into hydrocarbon rich bio-oil: Effects of nitrogen and carbon dioxide environment.

Bioresour Technol 2020 Oct 1;314:123758. Epub 2020 Jul 1.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing 400045,China.

Pyrolysis of Spirulina Platensis (SP) microalgae was carried out under different reaction environment such as nitrogen (N) and carbon dioxide (CO) at different reaction temperatures of 300, 350, 400, 450 and 500 °C. Catalytic upgradations were examined over solid acid (ZSM-5) and solid base (MgO) catalyst, and with ZSM-5-MgO catalysts mixtures. Results showed, pyrolysis of non-catalytic biomass yielded maximum bio-oil of 43.6% under N. However catalytic upgradation in CO environment produced lower bio-oil due to the coke formation. Maximum bio-oil (46.2 wt%) was obtained with basic metal MgO catalyst in N environment compared to other catalyst and environments. Mixture of MgO-ZSM-5 catalyst improved the bio-oil yield (37.8-48.6 wt%) compared to individual catalytic reaction under N and CO. Higher high heating value (HHV) was observed in catalytic bio-oil 36.8 MJ/Kg. Bio-oil (catalytic) analysis revealed that 64-70% of compounds are in hydrocarbon range. Bio-oil was rich in hydrocarbons of C-C range with less oxygenated compounds.
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http://dx.doi.org/10.1016/j.biortech.2020.123758DOI Listing
October 2020

Evaluation of population stratification adjustment using genome-wide or exonic variants.

Genet Epidemiol 2020 10 30;44(7):702-716. Epub 2020 Jun 30.

Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.

Population stratification may cause an inflated type-I error and spurious association when assessing the association between genetic variations with an outcome. Many genetic association studies are now using exonic variants, which captures only 1% of the genome, however, population stratification adjustments have not been evaluated in the context of exonic variants. We compare the performance of two established approaches: principal components analysis (PCA) and mixed-effects models and assess the utility of genome-wide (GW) and exonic variants, by simulation and using a data set from the Framingham Heart Study. Our results illustrate that although the PCs and genetic relationship matrices computed by GW and exonic markers are different, the type-I error rate of association tests for common variants with additive effect appear to be properly controlled in the presence of population stratification. In addition, by considering single nucleotide variants (SNVs) that have different levels of confounding by population stratification, we also compare the power across multiple association approaches to account for population stratification such as PC-based corrections and mixed-effects models. We find that while these two methods achieve a similar power for SNVs that have a low or medium level of confounding by population stratification, mixed-effects model can reach a higher power for SNVs highly confounded by population stratification.
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http://dx.doi.org/10.1002/gepi.22332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722041PMC
October 2020

Dissection of the genetic basis of oil content in Chinese peanut cultivars through association mapping.

BMC Genet 2020 06 8;21(1):60. Epub 2020 Jun 8.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, 430062, People's Republic of China.

Background: Peanut is one of the primary sources for vegetable oil worldwide, and enhancing oil content is the main objective in several peanut breeding programs of the world. Tightly linked markers are required for faster development of high oil content peanut varieties through genomics-assisted breeding (GAB), and association mapping is one of the promising approaches for discovery of such associated markers.

Results: An association mapping panel consisting of 292 peanut varieties extensively distributed in China was phenotyped for oil content and genotyped with 583 polymorphic SSR markers. These markers amplified 3663 alleles with an average of 6.28 alleles per locus. The structure, phylogenetic relationship, and principal component analysis (PCA) indicated two subgroups majorly differentiating based on geographic regions. Genome-wide association analysis identified 12 associated markers including one (AGGS1014_2) highly stable association controlling up to 9.94% phenotypic variance explained (PVE) across multiple environments. Interestingly, the frequency of the favorable alleles for 12 associated markers showed a geographic difference. Two associated markers (AGGS1014_2 and AHGS0798) with 6.90-9.94% PVE were verified to enhance oil content in an independent RIL population and also indicated selection during the breeding program.

Conclusion: This study provided insights into the genetic basis of oil content in peanut and verified highly associated two SSR markers to facilitate marker-assisted selection for developing high-oil content breeding peanut varieties.
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http://dx.doi.org/10.1186/s12863-020-00863-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282078PMC
June 2020

Genome-Wide Identification of Peanut Genes Reveals That and Are Involved in Regulating VLCFA Contents in Seeds.

Front Plant Sci 2020 7;11:406. Epub 2020 May 7.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Wuhan, China.

The peanut ( L.) is an important oilseed crop worldwide. Compared to other common edible vegetable oils, peanut oil contains a higher content of saturated fatty acids (SFAs), approximately 20-40% of which are very long chain fatty acids (VLCFAs). To understand the basis for this oil profile, we interrogated genes for peanut β-ketoacyl-CoA synthase (KCS), which is known to be a key enzyme in VLCFA biosynthesis. A total of 30 genes were identified in the assembled genome of the peanut. Based on transcriptome data, nine genes with high expression levels in developing seeds were cloned and expressed in yeast. All these AhKCSs could produce VLCFAs but result in different profiles, indicating that the AhKCSs catalyzed fatty acid elongation with different substrate specificities. Expression level analysis of these nine genes was performed in developing seeds from six peanut germplasm lines with different VLCFA contents. Among these genes, the expression levels of or were, 4-10-fold higher than that of any other . However, only the expression levels of and were significantly and positively correlated with the VLCFA content, suggesting that AhKCS1 and AhKCS28 were involved in the regulation of VLCFA content in the peanut seed. Further subcellular localization analysis indicated that AhKCS1 and AhKCS28 were located at the endoplasmic reticulum (ER). Overexpression of or in increased the contents of VLCFAs in the seed, especially for very long chain saturated fatty acids (VLCSFAs). Taken together, this study suggests that and could be key genes in regulating VLCFA biosynthesis in the seed, which could be applied to improve the health-promoting and nutritional qualities of the peanut.
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http://dx.doi.org/10.3389/fpls.2020.00406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221192PMC
May 2020

Widely tunable cavity-enhanced frequency combs.

Opt Lett 2020 Apr;45(7):2123-2126

We describe the cavity enhancement of frequency combs over a wide tuning range of 450-700 nm (${ \gt }7900\;{{\rm cm}^{ - 1}} $>7900cm), covering nearly the entire visible spectrum. Tunable visible frequency combs from a synchronously pumped optical parametric oscillator are coupled into a four-mirror, dispersion-managed cavity with a finesse of 600-1400. An intracavity absorption path length enhancement greater than 190 is obtained over the entire tuning range, while preserving intracavity spectral bandwidths capable of supporting sub-200 fs pulse durations. These tunable cavity-enhanced frequency combs can find many applications in nonlinear optics and spectroscopy.
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http://dx.doi.org/10.1364/OL.389412DOI Listing
April 2020

Silver nanoparticles doped TiO catalyzed Suzuki-coupling of bromoaryl with phenylboronic acid under visible light.

Authors:
Yuning Chen Li Feng

J Photochem Photobiol B 2020 Apr 25;205:111807. Epub 2020 Jan 25.

School of Civil and Transportation Engineering, Guangdong University of Technology, No100, Waihuan Xi Road, Guangzhou, Higher Education Mega Center, Panyu District, Guangzhou 510006, Guangdong, China. Electronic address:

The formation of the carbon‑carbon bond in the synthetic chemistry explored in many ways. Suzuki-cross coupling is one of the ways to make bonds between two carbon atoms of similar molecules or different molecules. CC bond was successfully formed between two aryl rings of aryl halides and phenylboronic acid at room temperature and atmospheric pressure under the visible illuminance. In this work we report, an in-situ synthesis of silver nanoparticles doped TiO nanoparticles (NPs) and studied its catalytic activity as an eco-friendly, simple, recyclable and efficient catalyst for one-pot Suzuki-coupling of bromoaryl with phenylboronic acid under visible light. Only, 45 mg of the catalyst resulted in a 98% conversion of p-ethyl bromobenzene with a 97% yield of p-ethyl biphenyl using toluene as the solvent in the presence of visible light at atmospheric pressure. The electron-donating groups (e.g., ethyl group) substituted bromobenzene resulted in the maximum yields than that of the substitution with the electron-withdrawing groups. The catalyst shown significant catalytic activity up to seven recycling runs without any loss. The doping of silver nanoparticles boosted the catalytic activity at titanium dioxide surface as well as inside the pores. The high surface area of the semiconductor support provides the sites for accommodated silver nanoparticles and shows enhanced reactivity towards the coupling reaction of bromoaryl with phenylboronic acid. The as-synthesized catalyst was thoroughly characterized by XRD, TEM, EDX, XPS, FTIR, TGA, UV-vis, Raman and BET analysis. The high recyclability of the photocatalyst remarked the footprints in the CC coupling reactions.
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http://dx.doi.org/10.1016/j.jphotobiol.2020.111807DOI Listing
April 2020

Discovery of two novel and adjacent QTLs on chromosome B02 controlling resistance against bacterial wilt in peanut variety Zhonghua 6.

Theor Appl Genet 2020 Apr 24;133(4):1133-1148. Epub 2020 Jan 24.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences (CAAS), Wuhan, 430062, China.

Key Message: Two novel and adjacent genomics and candidate genes for bacterial wilt resistance were identified on chromosome B02 in peanut variety Zhonghua 6 using both traditional QTL mapping and QTL-seq methods. Peanut (Arachis hypogaea) is an important oilseed crop worldwide. Utilization of genetic resistance is the most economic and effective approach to control bacterial wilt, one of the most devastating plant diseases, in peanut production. To accelerate the genetic improvement of bacterial wilt resistance (BWR) in peanut breeding programs, quantitative trait locus (QTL) mapping has been conducted for two resistant varieties. In this context, we deployed linkage mapping as well as sequencing-based mapping approach, QTL-seq, to identify genomic regions and candidate genes for BWR in another highly resistant variety Zhonghua 6. The recombination inbred line population (268 progenies) from the cross Xuhua 13 × Zhonghua 6 was used in BWR evaluation across five environments. QTL mapping using both SSR- and SNP-based genetic maps identified a stable QTL (qBWRB02-1) on chromosome B02 with 37.79-78.86% phenotypic variation explained (PVE) across five environments. The QTL-seq facilitated further dissection of qBWRB02-1 into two adjacent genomic regions, qBWRB02-1-1 (2.81-4.24 Mb) and qBWRB02-1-2 (6.54-8.75 Mb). Mapping of newly developed Kompetitive allele-specific PCR (KASP) markers on the genetic map confirmed their stable expressions across five environments. The effects of qBWRB02-1-1 (49.43-68.86% PVE) were much higher than qBWRB02-1-2 (3.96-6.48% PVE) and other previously reported QTLs. Nineteen putative candidate genes affected by 49 non-synonymous SNPs were identified for qBWRB02-1-1, and ten of them were predicted to code for disease resistance proteins. The major and stable QTL qBWRB02-1-1 and validated KASP markers could be deployed in genomics-assisted breeding (GAB) to develop improved peanut varieties with enhanced BWR.
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http://dx.doi.org/10.1007/s00122-020-03537-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064456PMC
April 2020

Study on ultrasound-assisted oxidative desulfurization for crude oil.

Ultrason Sonochem 2020 May 26;63:104946. Epub 2019 Dec 26.

The Second Clinical College of Guangzhou University of Chinese Medicine (Guangdong Provincial Academy of Chinese Medical Sciences), 55 Neihuanxi Road, Guangzhou 510006, China.

The existence of sulfur compounds in crude oil will bring many problems such as corrosion, catalyst poisoning and pollution to the petroleum processing process. Therefore, how to reduce the sulfur content as much as possible in the process of crude oil processing has become an important research topic in the petroleum processing industry. In this paper, ultrasonic-oxidative desulfurization is studied. The effects of reaction temperature, reaction time, amount of oxidant and demulsifier on desulfurization rate are investigated. And the effect of oxidative desulfurization and single oxidative desulfurization under ultrasonic treatment are compared. It is found that the addition of ultrasonic treatment can enhance the desulfurization effect of desulfurizer, the desulfurization efficiency can be increased by about 10% under ultrasonic treatment (100 W, 70 kHz); ultrasonic wave plays an auxiliary role in the system, it can promote heterogeneous reactions, improve the activity of oxidants, and promote the degradation of macromolecular compounds. Finally, physical desulfurization, chemical desulfurization and biological desulfurization technologies are compared.
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http://dx.doi.org/10.1016/j.ultsonch.2019.104946DOI Listing
May 2020

SNX3 suppresses the migration and invasion of colorectal cancer cells by reversing epithelial-to-mesenchymal transition via the β-catenin pathway.

Oncol Lett 2019 Nov 12;18(5):5332-5340. Epub 2019 Sep 12.

Medical Research Center, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan 610036, P.R. China.

The Wnt/β-catenin signaling pathway is a well-studied pathway that drives the carcinogenesis and metastasis of colorectal cancer (CRC). The secretion of Wnt proteins is essential for the continuous activation of Wnt/β-catenin signaling in CRC. The secretion of wingless, which is homologous to the human Wnt protein, is mediated by sorting nexin 3 (SNX3) in ; however, the role of SNX3 in CRC remains unknown. In the present study it was demonstrated that SNX3 reduced the migratory and invasive ability of HCT116 human CRC cells, and reversed epithelial-mesenchymal transition (EMT). Conversely, in the HT29 CRC cell line, which endogenously expresses high levels of SNX3, short hairpin RNA or siRNA-mediated knockdown of SNX3 induced EMT, and enhanced cell migration and invasion. In addition, upregulation of SNX3 significantly inhibited metastasis of HCT116 cells to the lungs of mice. These SNX3-mediated effects were associated with downregulation of β-catenin. Taken together, by downregulating β-catenin, SNX3 may mediate EMT and reverse CRC metastasis.
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http://dx.doi.org/10.3892/ol.2019.10860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781754PMC
November 2019

High-resolution mapping of a major and consensus quantitative trait locus for oil content to a ~ 0.8-Mb region on chromosome A08 in peanut (Arachis hypogaea L.).

Theor Appl Genet 2020 Jan 26;133(1):37-49. Epub 2019 Sep 26.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, 430062, People's Republic of China.

KEY MESSAGE: ddRAD-seq-based high-density genetic map comprising 2595 loci identified a major and consensus QTL with a linked marker in a 0.8-Mb physical interval for oil content in peanut. Enhancing oil content is an important breeding objective in peanut. High-resolution mapping of quantitative trait loci (QTLs) with linked markers could facilitate marker-assisted selection in breeding for target traits. In the present study, a recombined inbred line population (Xuhua 13 × Zhonghua 6) was used to construct a genetic map based on double-digest restriction-site-associated DNA sequencing (ddRAD-seq). The resulting high-density genetic map contained 2595 loci, and spanned a length of 2465.62 cM, with an average distance of 0.95 cM/locus. Seven QTLs for oil content were identified on five linkage groups, including the major and stable QTL qOCA08.1 on chromosome A08 with 10.14-27.19% phenotypic variation explained. The physical interval of qOCA08.1 was further delimited to a ~ 0.8-Mb genomic region where two genes affecting oil synthesis had been annotated. The marker SNPOCA08 was developed targeting the SNP loci associated with oil content and validated in peanut cultivars with diverse oil contents. The major and stable QTL identified in the present study could be further dissected for gene discovery. Furthermore, the tightly linked marker for oil content would be useful in marker-assisted breeding in peanut.
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http://dx.doi.org/10.1007/s00122-019-03438-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952344PMC
January 2020

Genome-wide expression quantitative trait locus analysis in a recombinant inbred line population for trait dissection in peanut.

Plant Biotechnol J 2020 03 17;18(3):779-790. Epub 2019 Sep 17.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, China.

The transcriptome connects genome to the gene function and ultimate phenome in biology. So far, transcriptomic approach was not used in peanut for performing trait mapping in bi-parental populations. In this research, we sequenced the whole transcriptome in immature seeds in a peanut recombinant inbred line (RIL) population and explored thoroughly the landscape of transcriptomic variations and its genetic basis. The comprehensive analysis identified total 49 691 genes in RIL population, of which 92 genes followed a paramutation-like expression pattern. Expression quantitative trait locus (eQTL) analysis identified 1207 local eQTLs and 15 837 distant eQTLs contributing to the whole-genome transcriptomic variation in peanut. There were 94 eQTL hot spot regions detected across the genome with the dominance of distant eQTL. By integrating transcriptomic profile and annotation analyses, we unveiled a putative candidate gene and developed a linked marker InDel02 underlying a major QTL responsible for purple testa colour in peanut. Our result provided a first understanding of genetic basis of whole-genome transcriptomic variation in peanut and illustrates the potential of the transcriptome-aid approach in dissecting important traits in non-model plants.
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http://dx.doi.org/10.1111/pbi.13246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004917PMC
March 2020

Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population.

Medicine (Baltimore) 2019 Aug;98(31):e16716

Department of Laboratory Medicine and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan.

The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population.Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed.The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation (P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes.This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.
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http://dx.doi.org/10.1097/MD.0000000000016716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709260PMC
August 2019

Carbenoxolone ameliorates hepatic lipid metabolism and inflammation in obese mice induced by high fat diet via regulating the JAK2/STAT3 signaling pathway.

Int Immunopharmacol 2019 Sep 29;74:105498. Epub 2019 Jun 29.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address:

Carbenoxolone (CBX) is the active principle of licorice, which is used to treat psoriasis, peptic ulcers, and wound healing. However, there is no report on how CBX ameliorates hepatic lipid metabolism and inflammation in obese mice. In this study, our aim is to explore the mechanism by which CBX regulates lipid metabolism in the liver of obese mice. C57BL/6J mice were divided into three groups and were fed with normal chow diet (NC group) or High-fat diet (HFD and CBX group) for eight weeks. Then mice in CBX group were given CBX every day by gavage for twelve weeks (15 mg/kg). Blood was collected for detection of triglycerides (TG), total cholesterol (TC), density lipoprotein (LDL), high-density lipoprotein (HDL), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST). Liver tissues were stained with hematoxylin-eosin for histological examination. Immunohistochemical staining was performed for detection of SOCS-3 (Suppressor of cytokine signaling 3), SREBP-1 (Sterol regulatory element-binding protein 1), and FAS (Fatty acid synthase) protein. The genes of SOCS-3, SREBP-1, and FAS in liver were assessed by real-time PCR. Western blotting was applied to detect the protein expressions of the phosphorylated JAK2 (Janus kinase 2) and phosphorylated STAT3 (Signal transducer and activator of transcription 3). Our results showed that compared with the HFD group, serum concentrations of TG, TC and LDL were decreased significantly, while the concentration of HDL was increased in the CBX group. CBX could attenuate intracellular lipid accumulation in the liver. Besides, treatment with CBX could significantly decrease levels of inflammatory factors such as IL-6 (Interleukin 6) and TNF-a (Tumor necrosis factor-a), increase expressions of phosphorylated JAK2 and phosphorylated STAT3, decrease the expressions of SOCS-3, SREBP-1 and FAS in the liver. In conclusion, through activating the JAK2/STAT3 signaling pathway in liver and reducing the expression of SCOCS-3, CBX could further decrease the expressions of SREBP-1c, FAS and ameliorate the inflammatory state of liver, so as to protecting the liver from lipid metabolism damage induced by high-fat diet. Therefore, CBX has the possibility for the treatment of obesity, hyperlipidemia, and inflammation.
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http://dx.doi.org/10.1016/j.intimp.2019.03.011DOI Listing
September 2019

Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype.

JAMA Neurol 2019 Sep;76(9):1099-1108

Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, Massachusetts.

Importance: Previous genome-wide association studies of common variants identified associations for Alzheimer disease (AD) loci evident only among individuals with particular APOE alleles.

Objective: To identify APOE genotype-dependent associations with infrequent and rare variants using whole-exome sequencing.

Design, Setting, And Participants: The discovery stage included 10 441 non-Hispanic white participants in the Alzheimer Disease Sequencing Project. Replication was sought in 2 independent, whole-exome sequencing data sets (1766 patients with AD, 2906 without AD [controls]) and a chip-based genotype imputation data set (8728 patients with AD, 9808 controls). Bioinformatics and functional analyses were conducted using clinical, cognitive, neuropathologic, whole-exome sequencing, and gene expression data obtained from a longitudinal cohort sample including 402 patients with AD and 647 controls. Data were analyzed between March 2017 and September 2018.

Main Outcomes And Measures: Score, Firth, and sequence kernel association tests were used to test the association of AD risk with individual variants and genes in subgroups of APOE ε4 carriers and noncarriers. Results with P ≤ 1 × 10-5 were further evaluated in the replication data sets and combined by meta-analysis.

Results: Among 3145 patients with AD and 4213 controls lacking ε4 (mean [SD] age, 83.4 [7.6] years; 4363 [59.3.%] women), novel genome-wide significant associations were obtained in the discovery sample with rs536940594 in AC099552 (odds ratio [OR], 88.0; 95% CI, 9.08-852.0; P = 2.22 × 10-7) and rs138412600 in GPAA1 (OR, 1.78; 95% CI, 1.44-2.2; meta-P = 7.81 × 10-8). GPAA1 was also associated with expression in the brain of GPAA1 (β = -0.08; P = .03) and its repressive transcription factor, FOXG1 (β = 0.13; P = .003), and global cognition function (β = -0.53; P = .009). Significant gene-wide associations (threshold P ≤ 6.35 × 10-7) were observed for OR8G5 (P = 4.67 × 10-7), IGHV3-7 (P = 9.75 × 10-16), and SLC24A3 (P = 2.67 × 10-12) in 2377 patients with AD and 706 controls with ε4 (mean [SD] age, 75.2 [9.6] years; 1668 [54.1%] women).

Conclusions And Relevance: The study identified multiple possible novel associations for AD with individual and aggregated rare variants in groups of individuals with and without APOE ε4 alleles that reinforce known and suggest additional pathways leading to AD.
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http://dx.doi.org/10.1001/jamaneurol.2019.1456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563544PMC
September 2019

The different responses of growth and photosynthesis to NH enrichments between Gracilariopsis lemaneiformis and its epiphytic alga Ulva lactuca grown at elevated atmospheric CO.

Mar Pollut Bull 2019 Jul 16;144:173-180. Epub 2019 May 16.

School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.

We investigated how elevated CO affects the responses of Gracilariopsis lemaneiformis and Ulva lactuca to NH enrichments. All algae were incubated under four nutritional conditions (zero addition, 100, 500, and 2500 μM NH), and two CO levels (390 ppm and 1000 ppm). The growth, photosynthesis, and soluble protein contents of both species increased under the eutrophication condition (100 μM NH). However, the growth and carotenoid contents of the two species declined when NH concentration increased. Under the super eutrophication condition (2500 μM NH), all indexes measured in G. lemaneiformis were suppressed, while the growth and photosynthesis in U. lactuca changed indistinctively, both compared with the control. Moreover, under the super eutrophication condition, elevated CO reduced the suppression in the growth of G. lemaneiformis, but decreased the growth of U. lactuca. Nonetheless, G. lemaneiformis displayed much lower growth rates than U. lactuca under the super eutrophication and elevated CO condition.
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http://dx.doi.org/10.1016/j.marpolbul.2019.04.049DOI Listing
July 2019

Next-generation sequencing identified genomic region and diagnostic markers for resistance to bacterial wilt on chromosome B02 in peanut (Arachis hypogaea L.).

Plant Biotechnol J 2019 12 31;17(12):2356-2369. Epub 2019 May 31.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences (CAAS), Wuhan, China.

Bacterial wilt, caused by Ralstonia solanacearum, is a devastating disease affecting over 350 plant species. A few peanut cultivars were found to possess stable and durable bacterial wilt resistance (BWR). Genomics-assisted breeding can accelerate the process of developing resistant cultivars by using diagnostic markers. Here, we deployed sequencing-based trait mapping approach, QTL-seq, to discover genomic regions, candidate genes and diagnostic markers for BWR in a recombination inbred line population (195 progenies) of peanut. The QTL-seq analysis identified one candidate genomic region on chromosome B02 significantly associated with BWR. Mapping of newly developed single nucleotide polymorphism (SNP) markers narrowed down the region to 2.07 Mb and confirmed its major effects and stable expressions across three environments. This candidate genomic region had 49 nonsynonymous SNPs affecting 19 putative candidate genes including seven putative resistance genes (R-genes). Two diagnostic markers were successfully validated in diverse breeding lines and cultivars and could be deployed in genomics-assisted breeding of varieties with enhanced BWR.
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http://dx.doi.org/10.1111/pbi.13153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835129PMC
December 2019

Carbenoxolone ameliorates insulin sensitivity in obese mice induced by high fat diet via regulating the IκB-α/NF-κB pathway and NLRP3 inflammasome.

Biomed Pharmacother 2019 Jul 15;115:108868. Epub 2019 Apr 15.

Department of Geriatrics, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.

The characteristic feature of obesity and insulin resistance is chronic low-grade inflammation. Nod-Like Receptor Pyrin 3 (NLRP3) inflammasome plays a central role in obesity-induced insulin resistance. However, how does Carbenoxolone (CBX) play its role in ameliorating insulin resistance in peripheral tissues of obese mice induced by high-fat diet (HFD) remains unknown. In our study, we explored the molecular mechanism of CBX in improving insulin resistance in liver and skeletal muscle in mice induced by the HFD. Our results revealed that in the CBX group, a significant decrease in fasting blood glucose, insulin and HOMA-IR score were observed. CBX could attenuate intracellular lipid accumulation and inflammation aggravation in liver and skeletal muscle. Besides, treatment with CBX could significantly reduce expressions of p-IκB-α, p-NF-κB, p-IRS-1, NLRP3 and inflammatory factors, increase expressions of p-PI3K and p-AKT. Therefore, CBX could dramatically improve insulin resistance in liver and skeletal muscle in mice induced by the high-fat diet. In conclusions, we demonstrate that CBX has a significant protective effect on diet-induced obesity in mice. The potential mechanisms include inhibiting IκB-α/NF-κB pathway, restricting the production of NLRP3 inflammasome and other inflammatory factors, reducing the expression of p-IRS-1, increasing the expressions of p-PI3K and p-AKT, thus ameliorating insulin resistance in liver and skeletal muscle of high-fat diet mice. Therefore CBX is an active agent against diet-induced obesity and is given the opportunity for the treatment of obesity related diseases.
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http://dx.doi.org/10.1016/j.biopha.2019.108868DOI Listing
July 2019

Identification of genomic regions and diagnostic markers for resistance to aflatoxin contamination in peanut (Arachis hypogaea L.).

BMC Genet 2019 03 12;20(1):32. Epub 2019 Mar 12.

Key Laboratory of Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture, Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Wuhan, China.

Background: Aflatoxin contamination caused by Aspergillus flavus is a major constraint to peanut industry worldwide due to its toxicological effects to human and animals. Developing peanut varieties with resistance to seed infection and/or aflatoxin accumulation is the most effective and economic strategy for reducing aflatoxin risk in food chain. Breeding for resistance to aflatoxin in peanut is a challenging task for breeders because the genetic basis is still poorly understood. To identify the quantitative trait loci (QTLs) for resistance to aflatoxin contamination in peanut, a recombinant inbred line (RIL) population was developed from crossing Zhonghua 10 (susceptible) with ICG 12625 (resistant). The percent seed infection index (PSII), the contents of aflatoxin B (AFB) and aflatoxin B (AFB) of RILs were evaluated by a laboratory kernel inoculation assay.

Results: Two QTLs were identified for PSII including one major QTL with 11.32-13.00% phenotypic variance explained (PVE). A total of 12 QTLs for aflatoxin accumulation were detected by unconditional analysis, and four of them (qAFB1A07 and qAFB1B06.1 for AFB, qAFB2A07 and qAFB2B06 for AFB) exhibited major and stable effects across multiple environments with 9.32-21.02% PVE. Furthermore, not only qAFB1A07 and qAFB2A07 were co-localized in the same genetic interval on LG A07, but qAFB1B06.1 was also co-localized with qAFB2B06 on LG B06. Conditional QTL mapping also confirmed that there was a strong interaction between resistance to AFB and AFB accumulation. Genotyping of RILs revealed that qAFB1A07 and qAFB1B06.1 interacted additively to improve the resistance to both AFB and AFB accumulation. Additionally, validation of the two markers was performed in diversified germplasm collection and four accessions with resistance to aflatoxin accumulation were identified.

Conclusions: Single major QTL for resistance to PSII and two important co-localized intervals associated with major QTLs for resistance to AFB and AFB. Combination of these intervals could improve the resistance to aflatoxin accumulation in peanut. SSR markers linked to these intervals were identified and validated. The identified QTLs and associated markers exhibit potential to be applied in improvement of resistance to aflatoxin contamination.
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http://dx.doi.org/10.1186/s12863-019-0734-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417274PMC
March 2019

Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Nat Genet 2019 03 28;51(3):414-430. Epub 2019 Feb 28.

Research Center and Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades-Universitat Internacional de Catalunya, Barcelona, Spain.

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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http://dx.doi.org/10.1038/s41588-019-0358-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463297PMC
March 2019
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