A novel bee-friendly peptidomimetic insecticide: Synthesis, aphicidal activity and 3D-QSAR study of insect kinin analogs at Phe2 modification.

BACKGROUND: As one of the most abundant and destructive pests in agriculture, aphids cause significant damage to crops due to their sap-taking and as virus vectors. Chemical insecticides are the most effective method to control aphids, but they bring insecticide resistance problems and harm nontarget organisms, especially bees, therefore the search for novel eco-friendly aphid control agents with low bee toxicity is urgent. Insect kinins are a class of small neuropeptides that control important functions in insects. In our previous study, we found insect kinin analog IV-3 has good aphicidal activity and the location of the aromatic ring on the side chain of Phe2 is the key to the formation of the ß-turn resulting in the biological activity of insect kinin analogs. However, there are few studies on insect kinin Phe2 substitution and modification, and its structure-activity relationship is still unclear. RESULTS: In this project, 44 insect kinin analogs with the Phe2 modification, replacing it with different natural or unnatural amino acids, were designed and synthesized based on the lead IV-3 to explore the role of the Phe2 residues. Bioassays with soybean aphids of Aphis glycines indicated that nine analogs have better aphicidal activity than the lead IV-3. In particular, compound L25 exhibits excellent aphicidal activity (LC50  = 0.0047 mmol L-1 ) and has low toxicity to bees. Furthermore, a reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) was established to produce a helpful clue that introducing hydrophobic groups away from the backbone chain is beneficial to improve aphicidal activity. CONCLUSION: The residue Phe2 of insect kinin analogs is the key position and has a significant impact on the activity. L25 has a high toxicity for aphids, while a low toxicity to bees, and therefore can be considered as a lead compound to develop new biosafe aphid control agents. Finally, we provide a useful 3D-QSAR model as theoretical guidance for further structural optimization. © 2022 Society of Chemical Industry.

Features of resolving and nonresolving indeterminate pulmonary nodules at follow-up CT: the NELSON study.

PURPOSE: To retrospectively identify features that allow prediction of the disappearance of solid, indeterminate, intraparenchymal nodules detected at baseline computed tomographic (CT) screening of individuals at high risk for lung cancer. MATERIALS AND METHODS: The study was institutional review board approved. Participants gave informed consent. Participants with at least one noncalcified, solid, indeterminate, intraparenchymal nodule (volume range, 50-500 mm(3)) at baseline were included (964 nodules in 750 participants). According to protocol, indeterminate nodules were re-examined at a 3-month follow-up CT examination. Repeat screening was performed at years 2 and 4. A nodule was defined as resolving if it did not appear at a subsequent CT examination. Nodule resolution was regarded as spontaneous, not the effect of treatment. CT features of resolving and nonresolving (stable and malignant) nodules were compared by means of generalized estimating equations analysis. RESULTS: At subsequent screening, 10.1% (97 of 964) of the nodules had disappeared, 77.3% (n = 75) of these at the 3-month follow-up CT and 94.8% (n = 92) at the second round of screening. Nonperipheral nodules were more likely to resolve than were peripheral nodules (odds ratio: 3.16; 95% confidence interval: 1.76, 5.70). Compared with smooth nodules, nodules with spiculated margins showed the highest probability of disappearance (odds ratio: 4.36; 95% confidence interval: 2.24, 8.49). CONCLUSION: Approximately 10% of solid, intermediate-sized, intraparenchymal pulmonary nodules found at baseline screening for lung cancer resolved during follow-up, three-quarters of which had disappeared at the 3-month follow-up CT examination. Resolving pulmonary nodules share CT features with malignant nodules.

Comparison of three software systems for semi-automatic volumetry of pulmonary nodules on baseline and follow-up CT examinations.

BACKGROUND: Early diagnosis of lung cancer in a treatable stage is the main purpose of lung cancer screening by computed tomography (CT). Accurate three-dimensional size and growth measurements are essential to assess the risk of malignancy. Nodule volumes can be calculated by using semi-automated volumetric software. Systematic differences in volume measurements between packages could influence nodule categorization and management decisions. PURPOSE: To compare volumetric measurements of solid pulmonary nodules on baseline and follow-up CT scans as well as the volume doubling time (VDT) for three software packages. MATERIAL AND METHODS: From a Lung Cancer Screening study (NELSON), 50 participants were randomly selected from the baseline round. The study population comprised participants with at least one pulmonary nodule at the baseline and consecutive CT examination. The volume of each nodule was determined for both time points using three semi-automated software packages (P1, P2, and P3). Manual modification was performed when automated assessment was visually inaccurate. VDT was calculated to evaluate nodule growth. Volume, VDT, and nodule management were compared for the three software packages, using P1 as the reference standard. RESULTS: In 25 participants, 147 nodules were present on both examinations (volume: 12.0-436.6 mm(3)). Initial segmentation at baseline was evaluated to be satisfactory in 93.9% of nodules for P1, 84.4 % for P2, and 88.4% for P3. Significant difference was found in measured volume between P1 and the other two packages (P < 0.001). P2 overestimated the volume by 38 ± 24%, and P3 by 50 ± 22%. At baseline, there was consensus on nodule size categorization in 80% for P1&P2 and 74% for P1&P3. At follow-up, consensus on VDT categorization was present in 47% for P1&P2 and 44% for P1&P3. CONCLUSION: Software packages for lung nodule evaluation yield significant differences in volumetric measurements and VDT. This variation affects the classification of lung nodules, especially in follow-up examinations.

Molecular characterization of a dehydroascorbate reductase from Pinus bungeana.

Abstract Dehydroascorbate reductase (DHAR) plays a critical role in the ascorbate-glutathione recycling reaction for most higher plants. To date, studies on DHAR in higher plants have focused largely on Arabidopsis and agricultural plants, and there is virtually no information on the molecular characteristics of DHAR in gymnosperms. The present study reports the cloning and characteristics of a DHAR (PbDHAR) from a pine, Pinus bungeana Zucc. ex Endl. The PbDHAR gene encodes a protein of 215 amino acid residues with a calculated molecular mass of 24.26 kDa. The predicted 3-D structure of PbDHAR showed a typical glutathione S-transferase fold. Reverse transcription-polymerase chain reaction revealed that the PbDHAR was a constitutive expression gene in P. bungeana. The expression level of PbDHAR mRNA in P. bungeana seedlings did not show significant change under high temperature stress. The recombinant PbDHAR was overexpressed in Escherichia coli following purification with affinity chromatography. The recombinant PbDHAR exhibited enzymatic activity (19.84 micromol/min per mg) and high affinity (a K(m) of 0.08 mM) towards the substrates dehydroascorbate (DHA). Moreover, the recombinant PbDHAR was a thermostable enzyme, and retained 77% of its initial activity at 55 degrees C. The present study is the first to provide a detailed molecular characterization of the DHAR in P. bungeana.