Search

Additional file 2: Supplementary Figure S1. SNP distribution. The number of SNPs within a 1 Mb window size distribute across all chromosomes. The color from green to red represents the gradual increasing SNP number in each window. Supplementary Figure S2. Principal Component Analysis. PCA was conducted on the SNP information of each sample using the GCTA tool. The blue, red, green, cyan and black dots represent SL1 - SL5 populations, respectively. Supplementary Figure S3. Linkage disequilibrium analysis. The numbers in each diamond-shaped box represent the correlation coefficients R2 between two SNPs, and the R2 > 0.2 was considered to indicate linkage. Supplementary Figure S4-S15. GWAS based on body weight from birth (Figure S4) to 110 days old ( Figure S15).

Since the exploitation of mineral resources results in the release of radionuclides, and consuming radionuclides affects public health in the short and long term. A case study of the environmental radiation impact from coal mining and germanium processing was carried out in southwest China. The coal mines contain germanium and uranium and have been exploited for more than 40 years. The farmlands around the site of coal mining and germanium processing have been contaminated by the solid waste and mine water in some extend since then. Samples of crops have been collected from contaminated farmlands in research area. The research area covers a radius of 5 km, in which there are 2 coal mines located. 210Pb and 210Po have been analyzed as the key radionuclides during monitoring program. The average activity concentrations of 210Pb and 210Po in the crops were 1.38 and 1.32 Bq/kg in cereals, 4.07 and 2.19 Bq/kg in leafy vegetables and 1.63 and 1.32 Bq/kg in root vegetables. The annual effective doses due to the ingestion of 210Pb and 210Po in consumed crops have been estimated for adult residents living in research area. The average annual effective dose was 0.336mSv/a, while the minimum was 0.171 mSv/a and the maximum was 0.948 mSv/a. The results show that crops grown on contaminated farmland contained an enhanced level of radioactivity concentration. Ingestion doses of local residents in research area were significantly higher than the China average level of 0.112 mSv/a, and the world average level of 0.042 mSv/a through 210Pb and 210Po in crops intake respectively.

The mode of action is the basis for the rational design of the novel agrochemicals. 3-(4-Methyl-1,2,3-thiadiazolyl)-6-trichloromethyl [1,2,4]triazolo [3,4-b][1,3,4]thiadiazole (YZK-C22) is a novel fungicide candidate. The aim of this study was identification of the mechanism of YZK-C22 against fungi. The results indicated that YZK-C22 inhibited the mycelial growth and spore germination of Botrytis cinerea. Total 56 differentially expressed proteins (DEPs) including 27 up regulated and 29 down regulated proteins were identified by isobaric tags for relative and absolute quantification (iTRAQ). The DEPs mainly concentrated on metabolic pathways, and the results were consistent across the studies of RNA and protein platforms. The pyruvate kinase (PK) activity in the glycolytic pathway was inhibited over 50% by 20 μg/mL of YZK-C22. Molecular docking analysis also validated that YZK-C22 could dock into the active centre of the PK instead of phosphoenolpyruvate. In summary, iTRAQ was an effective way for target identification of YZK-C22.

Background Plant viral diseases cause tremendous decreases in yield and quality. Natural polycyclic compounds such as those containing carbocycles are often very important lead compounds for drug and pesticide development. Tricyclic spiranoid lactones with 5A 5B 6C -ring fusion topologies possess various bioactivities. In this study, 33 new 5A 5B 6C tricyclic spirolactones were rationally designed, synthesized, characterized and evaluated for antiviral activities. Result These compounds showed no apparent toxicity against Italian honeybees up to 2.73 µg bee-1 . Spirolactones 14, 16, 19, 23 and 28 at a concentration of 100 µg mL-1 inactivated 90% of tobacco mosaic virus (TMV) infection, making these compounds much more potent than the positive controls. Significantly, compound 19 displayed the best inactivation activity causing inhibition of up to 98%. Conclusion The results of the bioassays and QSAR studies indicated that the carbon-containing cyclic moiety was the antiviral pharmacophore, and derivative 19, which showed the best inactivation activity, could emerge as a potential antiviral agent against TMV. In vitro capsid protein (CP) assembly and TMV assembly inhibition determinations indicated that these compounds induced crosslinking in the TMV and prevented its uncoating, which was a putative new mode of action for TMV inactivation. © 2018 Society of Chemical Industry.

An efficient, convenient short synthetic procedure for the synthesis of the intricate 5A5B6C-ring fusion topologies of tricyclic spiranoid β-hydroxybutyrolactones through lactonization of the key intermediate trans-α-hydroxyindenones with malonates is described. All the compounds synthesized exhibited environmentally benign characteristics, moderate fungicidal, nematocidal, and anti-TMV activities.

To contribute molecular diversity for novel fungicide development, a series of novel thiazole carboxamides were rationally designed, synthesized, and characterized with the succinate dehydrogenase (SDH) as target. Bioassay indicated that compound 6g showed the similar excellent SDH inhibition as that of Thifluzamide with IC50 of 0.56 mg/L and 0.55 mg/L, respectively. Some derivatives displayed improved in vitro fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum with EC50 of 1.2–16.4 mg/L and 0.5–1.9 mg/L. Surprisingly, 6g showed promising in vitro fungicidal activities against R. cerealis and S. sclerotiorum with EC50 of 6.2 and 0.6 mg/L, respectively, which was superior to Thifluzamide with the EC50 of 22.1 and 4.4 mg/L, respectively. Additionally, compounds 6c and 6g displayed excellent in vivo fungicidal activities against S. sclerotiorum on Brassica napus L. leaves with protective activity of 75.4% and 67.3% at 2.0 mg/L, respectively, while Thifluzamide without activity at...

Oxathiapiprolin is one of the best active fungicides discovered for oomycetes control. To develop a fungicide candidate with a broad spectrum of activity, 22 new piperidinylthiazole derivatives were designed and synthesized. Compound 5l showed the best activity against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo with 100% and 80% of inhibition, respectively, at 1 mg/L, and 72.87% of field efficacy against P. cubensis at 1 g ai/667 m2 validated these results. Compound 5i exhibited a broad spectrum of excellent activity against Sclerotinia sclerotiorum with EC50 = 0.30 mg/L (>10 times more active than oxathiapiprolin and azoxystrobin in vitro), good activity against Botrytis cinerea, Cercospora arachidicola, and Gibberella zeae with EC50 of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and 30% inhibition rates, respectively, at 1 mg/L in vivo. Mode of action studies by RNA sequencing analysis discovered oxysterol-binding protein (OSBP), chitin synthase (CHS1), and (1,3)-β-glucan synthase (FKS2) as the potent target of 5i against S. sclerotiorum. Quenching studies validated that OSBP was the same target of both 5i and oxathiapiprolin; it was quenched by both of them. Our studies discovered isothiazole-containing piperidinylthiazole as an OSBP target-based novel lead for fungicide development.

3,4-Dichloroisothiazoles can induce systemic acquired resistance (SAR) to enhance plant resistance against a subsequent pathogen attack, and oxathiapiprolin exhibits excellent anti-fungal activity against oomycetes targeting at the oxysterol-binding protein. To discover novel chemicals with systemic acquired resistance and fungicidal activity, 21 novel isothiazole-thiazole derivatives were designed, synthesized and characterized according to the active compound derivatization method. Compound 6u, with EC 50 values of 0.046 mg L −1 and 0.20 mg L −1 against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo, might act at the same target as oxysterol binding protein (PcORP1) of oxathiapiprolin; this result was validated by cross-resistance and molecular docking studies. The expression of the systemic acquired resistance gene pr1 was significantly up-regulated after treating with compound 6u for 24 h (43-fold) and 48 h (122-fold). These results can help the development of isothiazole-thiazole-based novel fungicides. © The Royal Society of Chemistry. This work was supported by the National Natural Science Foundation of China (No. 31571991 and No. 31872007), the Tianjin Natural Science Foundation (No. 18JCZDJC33500), the China Postdoctoral Science Foundation (No. 2017M611156) and the International Science & Technology Cooperation Program of China (No. 2014DFR41030). The authors also thank Dr Jiaxing Huang for providing pyrazole compounds (synthesized in the Key Technologies R&D program of China, 2015BAK45B01, CAU) for model reaction. The authors are grateful to the research team of Professor Xi-Li Liu at CAU for their help of determination of the active compounds against oxathiapiprolin-resistant fungi. Kalinina T. A. thanks the Russian Foundation for Basic Research (Grant No. 18-316-20018).

A molecular design approach was used in our laboratory to guide the development of imidazole-based fungicides. Based on homology modeling and molecular docking studies targeting the cytochrome P450-dependent sterol 14α-demethylase, 3,4-dichloroisothiazole-based imidazoles showed great potential. Several such compounds were then rationally designed, synthesized, characterized, and their antifungal activities were evaluated. Bioassay results showed that compounds such as ( R)-11, ( R)-12, and ( S)-11 have commendable, broad-spectrum antifungal activities that are comparable to those of commercial products. Based on Q-PCR testing and microscopy observations, the imidazole derivatives affect fungal cell wall formation through the inhibition of the BcCYP51 expression system. These findings strongly suggest that the mode of action of these imidazole compounds is similar to that of tioconazole and imazalil. This report indicates that this molecular design strategy is not only practical but productive.