Conformationally Strained trans- Cyclooctene (sTCO) Enables the Rapid Construction of 18 F-PET Probes via Tetrazine Ligation

The bioorthogonal reaction between tetrazines and trans-cyclooctenes is a method for the rapid construction of F-18 probes for PET imaging. Described here is a second generation 18F-labeling system based on a conformationally strained trans-cyclooctene (sTCO)—a dienophile that is approximately 2 orders of magnitude more reactive than conventional TCO dienophiles. Starting from a readily prepared tosylate precursor, an 18F labeled sTCO derivative (18F-sTCO) could be synthesized in 29.3 +/- 5.1% isolated yield and with high specific activity. Tetrazine ligation was carried out with a cyclic RGD-conjugate of a diphenyl-s-tetrazine analogue (RGD-Tz) chosen from a diene class with an excellent combination of fast reactivity and stability both for the diene as well as the Diels-Alder adduct. For both the tetrazine and the sTCO, mini-PEG spacers were included to enhance solubility and improve the in vivo distribution profile of the resulting probe. Extremely fast reactivity (up to 2.86 x 105 M-1s-1 at 25 °C in water) has been observed in kinetic studies in the reaction of sTCO with diphenyl-s-tetrazine derivatives. A kinetic study on sTCO diastereomers in 55:45 MeOH:water showed that the syn-diastereomer displayed slightly faster reactivity than the anti-diastereomer. An 18F-sTCO conjugate with RGD-Tz demonstrated prominent and persistent tumor uptake in vivo with good tumor-to-background contrast. Unlike most radiolabeled RGD peptides, the tumor uptake of this PET agent increased from 5.3 +/- 0.2% ID/g at 1 h post injection (p.i.), to 8.9 +/- 0.5% ID/g at 4 h p.i., providing evidence for prolonged blood circulation. These findings suggest that tetrazine ligations employing 18F-sTCO should serve as a powerful and general platform for the rapid construction of peptide or protein derived PET agents

Impacts of climate change on suitability zonation for potato cultivation in Jilin Province, Northeast China

Global climate change is causing notable shifts in the environmental suitability of the main regions involved in potato cultivation and has, thus, changed the production potential of potatoes. These shifts can be mapped at fine scales to better understand climate change within areas of potato cultivation and to find infrastructural- and breeding-based solutions. As a case study, we have identified and mapped the structural and spatial shifts that occurred in areas suitable for potato cultivation in Jilin Province, China. We identified a discontinuity in climate change trends between 1961 and 2018 based on data for Jilin Province, and analyzed the averages and linear trends for six important climatic parameters. We used the averages of these climatic parameters to establish climate models for the province and determined cultivation using a multi-criteria, decision-based model that integrates Analytical Hierarchy Process Weighted Principal Component Analysis (AHP-PCA) and Geographic Information System (GIS). We mapped the environmentally suitable areas for potato cultivation at a 3-km resolution based on the geo-climate model for each time period and analyzed differences between them. We found that Most suitable areas for potato cultivation were mainly distributed in the central area of Jilin Province, Suitable areas were located in the northwestern plains, and Sub-suitable areas were located in the eastern mountainous areas. In contrast, Not suitable areas occur mainly in the high-altitude areas in the east. The areas of Most suitable and Suitable areas for potato cultivation in Jilin Province were increasing, with increasing rates of 0.37 x 1,000 km(2) decade(-1) (R-2 = 0.58, P < 0.01) and 0.20 x 1,000 km(2) decade(-1) (R-2 = 0.28, P < 0.01), respectively, while the extent of Sub-suitable areas is decreasing, with a decreasing rate of 0.58 x 1,000 km(2) decade(-1) (R-2 = 0.53, P < 0.05). The area of Not suitable areas had undergone little change. Most suitable and Suitable areas for potato cultivation showed a trend towards northward expansion. Overall, our results suggest that global climate change has had a positive impact on potato cultivation in Jilin Province over the past 58 years

Progress in carbon-based electrocatalyst derived from biomass for the hydrogen evolution reaction

Hydrogen evolution reaction (HER) involving electrocatalytic process is established as a promising and non-pollution method for hydrogen production. The cheap alternatives of precious-metal electrocatalysts with high activity and robust stability is essential for the high-scale application of electrocatalytic hydrogen evolution. Recently, carbon-based electrocatalysts derived from biomass have attracted more and more attentions with thanks to their characteristics as low-cost, renewable, abundantly distributed and environmentally friendly. In this work, the original carbon material derived from biomass and the one doped with N and/or S as HER electrocatalysts are intensively overviewed regarding to the electrochemical performance and hydrogen yield. The overpotential at 10 mA cm (η ) is generally greater than 100 mV, which is far inferior to Pt-based catalysts. Consequently, biomass-based carbon materials decorated by transition metal and/or trace amount precious metal were introduced for improving the HER performance. The synergistic effect between metals and heteroatoms can significantly enhance the electrocatalytic activity, and the smallest value of η is 10 mV. The limitations and challenges in this area were also addressed as (1) the in-depth investigation of conversion and electrocatalytic mechanism, (2) metal modification via in-situ growth, (3) the reproducibility for biomass transformation, and (4) the catalyst assembly with renewable energy equipment. −2 10 1

BcGR1.1, a Cytoplasmic Localized Glutathione Reductase, Enhanced Tolerance to Copper Stress in Arabidopsis thaliana

Copper is a mineral element, which is necessary for the normal growth and development of plants, but high levels of copper will seriously damage plants. Studies have shown that AtGR1 improves the tolerance of Arabidopsis to aluminum and cadmium stress. However, the role of GR in the copper stress response of plants is still unclear. Here, we identified four genes (named BcGR1.1, BcGR1.2, BcGR2.1 and BcGR2.2, respectively) encoding glutathione reductase (GR) in non-heading Chinese cabbage (Brassica campestris (syn. Brassica rapa) ssp. chinensis), which could be divided into two types based on the subcellular localization. Among them, BcGR1.1, which belonged to the cytoplasmic localization type, was significantly upregulated under copper stress. Compared to WT (the wild type), Arabidopsis thaliana heterologously overexpressed BcGR1.1 had longer roots, higher fresh weight, higher GSH levels and GSH/GSSG (oxidized form of GSH) ratio, and accumulated more superoxide dismutase and peroxidase under copper stress. However, in the AsA-GSH cycle under copper stress, the contents of AsA and AsA/DHA were significantly downregulated, and the contents of DHA and T-AsA (total AsA) were upregulated, in the BcGR1.1-overexpressing Arabidopsis. Therefore, BcGR1.1 could improve the scavenging ability of reactive oxygen species (ROS) by increasing the activity of GR, antioxidant enzymes and the utilization of AsA, and then enhance the copper stress tolerance of plants

Conformationally Strained trans-Cyclooctene (sTCO) Enables the Rapid Construction of F-18-PET Probes via Tetrazine Ligation

Publisher's PDFThe bioorthogonal reaction between tetrazines and trans-cyclooctenes is a method for the rapid construction of F-18 probes for PET imaging. Described here is a second generation F-18-labeling system based on a conformationally strained trans-cyclooctene (sTCO)-a dienophile that is approximately 2 orders of magnitude more reactive than conventional TCO dienophiles. Starting from a readily prepared tosylate precursor, an F-18 labeled sTCO derivative (F-18-sTCO) could be synthesized in 29.3 +/- 5.1% isolated yield and with high specific activity. Tetrazine ligation was carried out with a cyclic RGD-conjugate of a diphenyl-s-tetrazine analogue (RGD-Tz) chosen from a diene class with an excellent combination of fast reactivity and stability both for the diene as well as the Diels-Alder adduct. For both the tetrazine and the sTCO, mini-PEG spacers were included to enhance solubility and improve the in vivo distribution profile of the resulting probe. Extremely fast reactivity (up to 2.86 x 10(5) M(-1)s(-1) at 25 degrees C in water) has been observed in kinetic studies in the reaction of sTCO with diphenyl-s-tetrazine derivatives. A kinetic study on sTCO diastereomers in 55:45 MeOH:water showed that the syn-diastereomer displayed slightly faster reactivity than the anti-diastereomer. An F-18-sTCO conjugate with RGD-Tz demonstrated prominent and persistent tumor uptake in vivo with good tumor-to-background contrast. Unlike most radiolabeled RGD peptides, the tumor uptake of this PET agent increased from 5.3 +/- 0.2% ID/g at 1 h post injection (p.i.), to 8.9 +/- 0.5% ID/g at 4 h p.i., providing evidence for prolonged blood circulation. These findings suggest that tetrazine ligations employing F-18-sTCO should serve as a powerful and general platform for the rapid construction of peptide or protein derived PET agents.University of Delaware, Department of Chemistry and Biochemistr