Identification of Two Novel QTL for Fusarium Head Blight Resistance in German Wheat Cultivar Centrum.

Fusarium head blight (FHB) is a devastating disease that occurs in warm and humid environments. The German wheat 'Centrum' has displayed moderate to high levels of FHB resistance in the field for many years. In this study, an F6:8 recombinant inbred line (RIL) population derived from cross 'Centrum' × 'Xinong 979' was evaluated for FHB response following point inoculation in five environments. The population and parents were genotyped using the GenoBaits Wheat 16 K Panel. Stable quantitative trait loci (QTL) associated with FHB resistance in 'Centrum' were mapped on chromosome arms 2DS and 5BS. The most effective QTL, located in 2DS, was identified as a new chromosome region represented by a 1.4 Mb interval containing 17 candidate genes. Another novel QTL was mapped in chromosome arm 5BS of a 5BS to 7BS translocation chromosome. In addition, two environmentally sensitive QTL were mapped on chromosome arms 2BL from 'Centrum' and 5AS from 'Xinong 979'. Polymorphisms of flanking phenotypic variance explained (PVE) markers (allele-specific quantitative PCR [AQP]) AQP-6 for QFhb.nwafu-2DS and 16K-13073 for QFhb.nwafu-5BS were validated in a panel of 217 cultivars and breeding lines. These markers could be useful for marker-assisted selection (MAS) of FHB resistance and provide a starting point for fine mapping and marker-based cloning of the resistance genes.

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells.

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.

Slow stripe rusting in Chinese wheat Jimai 44 conferred by Yr29 in combination with a major QTL on chromosome arm 6AL.

KEY MESSAGE: YrJ44, a more effective slow rusting gene than Yr29, was localized to a 3.5-cM interval between AQP markers AX-109373479 and AX-109563479 on chromosome 6AL. "Slow rusting" (SR) is a type of adult plant resistance (APR) that can provide non-specific durable resistance to stripe rust in wheat. Chinese elite wheat cultivar Jimai 44 (JM44) has maintained SR to stripe rust in China since its release despite exposure to a changing and variable pathogen population. An F2:6 population comprising 295 recombinant inbred lines (RILs) derived from a cross between JM44 and susceptible cultivar Jimai 229 (JM229) was used in genetic analysis of the SR. The RILs and parental lines were evaluated for stripe rust response in five field environments and genotyped using the Affymetrix Wheat55K SNP array and 13 allele-specific quantitative PCR-based (AQP) markers. Two stable QTL on chromosome arms 1BL and 6AL were identified by inclusive composite interval mapping. The 1BL QTL was probably the pleiotropic gene Lr46/Yr29/Sr58. QYr.nwafu-6AL (hereafter named YrJ44), mapped in a 3.5-cM interval between AQP markers AX-109373479 and AX-109563479, was more effective than Yr29 in reducing disease severity and relative area under the disease progress curve (rAUDPC). RILs harboring both YrJ44 and Yr29 displayed levels of SR equal to the resistant parent JM44. The AQP markers linked with YrJ44 were polymorphic and significantly correlated with stripe rust resistance in a panel of 1,019 wheat cultivars and breeding lines. These results suggested that adequate SR resistance can be obtained by combining YrJ44 and Yr29 and the AQP markers can be used in breeding for durable stripe rust resistance.

Epistatic interaction effect between chromosome 1BL (Yr29) and a novel locus on 2AL facilitating resistance to stripe rust in Chinese wheat Changwu 357-9.

KEY MESSAGE: Four stable QTL for adult plant resistance were identified in wheat line Changwu 357-9, including a new QTL on 2AL showing significant interaction with Yr29 to reduce stripe rust severity. Stripe rust (yellow rust) is a serious disease of bread wheat (Triticum aestivum L.) worldwide. Genetic resistance is considered the most economical, effective and environmentally friendly method to control the disease and to minimize the use of fungicides. The current study focused on characterizing the components of stripe rust resistance and understanding the interactions in Changwu 357-9 (CW357-9)/Avocet S RIL population. A genetic linkage map constructed using a new GenoBaits Wheat 16K Panel and the 660K SNP array had 5104 polymorphic SNP markers spanning 3533.11 cM. Four stable QTL, consistently identified across five environments, were detected on chromosome arms 1BL, 2AL, 3DS, and 6BS in Changwu357-9. The most effective QTL QYrCW357-1BL was Yr29. The 6BS QTL was identified as Yr78, which has been combined with the 1BL QTL in many wheat cultivars and breeding lines. The novel QTL on 2AL with moderate effect showed a stable and significant epistatic interaction with Yr29. The QTL on 3DL should be same as QYrsn.nwafu-3DL and enriches the overall stripe rust resistance gene pool for breeding. Polymorphisms of flanking AQP markers AX-110020417 (for QYrCW357-1BL), AX-110974948 (for QYrCW357-2AL), AX-109466386 (for QYrCW357-3DL), and AX-109995005 (for QYrCW357-6BS) were evaluated in a diversity panel including 225 wheat cultivars and breeding lines. These results suggested that these high-throughput markers could be used to introduce QYrCW357-1BL, QYrCW357-2AL, QYrCW357-3DL, and QYrCW357-6BS into commercial wheat cultivars. Combinations of these genes with other APR QTL should lead to higher levels of stripe rust resistance along with the beneficial effects of multi-disease resistance gene Yr29 on improving resistance to other diseases.

Bistatic Doppler wind lidar study for wind field measurement over complex terrain.

Atmospheric wind measurement over complex terrain is of great significance. Due to the limitation of the retrieval method, a single wind lidar cannot be applied to detect the horizontally inhomogeneous wind field. Therefore, a bistatic Doppler wind lidar system is studied for meeting the requirement of wind detection over complex terrain. By analyzing the uncertainty of a synthetic wind field, the isosceles triangle is proven to be the optimal layout of the bistatic lidar system. By using the data set of Nanjing sounding data from 2015 and two typical wind field models, the detection accuracy of the bistatic lidar system is estimated. The experimental results show that the bistatic wind lidar can detect the wind field over complex terrain accurately, the wind errors are less than 1 m/s below 4 km, and the relative errors are less than 5%.

Impact of solar background radiation on the accuracy of wind observations of spaceborne Doppler wind lidars based on their orbits and optical parameters.

Due to the quantum properties of light, solar background radiation (SBR) is the main source of noise in daytime wind observations of spaceborne Doppler wind lidars (DWLs). In previous works, the impact of SBR on the observation accuracy of spaceborne lidars was assessed mainly using the default or worst-case scenarios. We assessed the impact of SBR on the observations of spaceborne DWLs using the global distributions of SBR in summer and winter, which were obtained based on their orbit parameters, view geometry and optical parameters. Three experiments illustrate that the uncertainty in wind observations increases with an increase in the quantiles of SBR. The uncertainties of the whole profiles of wind are greater than 2 m s-1 in the troposphere and 3 m s-1 in the stratosphere when the quantile of the SBR is greater than 85% in summer and 95% in winter, which do not satisfy the accuracy expectations of the European Space Agency (ESA) for spaceborne DWLs. The facts indicate that the impact of SBR cannot be negligible for the observations of spaceborne DWLs. Based on the orbit parameters, view geometry, and optical parameters of new spaceborne DWLs, engineers can assess the impact of SBR on the accuracy of wind observations from a global perspective using the method proposed in this paper.

BH3 mimetics derived from Bim-BH3 domain core region show PTP1B inhibitory activity.

A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD = 8.38 nmol/L), inhibitory activity (IC50 = 1.20 µmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model. These results may indicate a new direction for the application of BH3 peptide mimetics and promising PTP1B peptide inhibitors could be designed and developed based on SM-6.

Simulation and assessment of solar background noise for spaceborne lidar.

The properties for six typical land cover types and three sky conditions were derived in this paper, which allows to make seasonal upper estimations of solar background radiation for a given atmospheric scenario. Solar background noise can be derived from the estimations for a spaceborne lidar based on optical parameters. Comparisons among simulated solar background noise and measurements of Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and a Moderate Resolution Imaging Spectroradiometer (MODIS) demonstrate the feasibility of this method. The upper estimates of solar background radiation can be used for lidar engineers to assess the upper estimates of solar background noise for given atmospheric scenarios, which would be a step forward in comparison with using the worst-case scenario everywhere.

[An in vitro self-ligation-based method for constructing infectious DNA clone of porcine circovirus type 2].

The aim of this study was to establish a rapid method for constructing infectious clones of porcine circovirus type 2 (PCV2). In this study, we constructed circular infectious clones of PCV2 by seamless cloning technology, using the clinically isolated strain PCV2-LX as a template. Meanwhile, this method was compared with the conventional restriction-ligation approach, focusing on the in vitro circularization (self-ligation) process of the genome and the growth characteristics of rescued viruses. The results showed that this method eliminates the need to analyze and introduce restriction endonuclease sites, thus avoiding the complexities associated with traditional restriction enzyme-based cloning steps. It offers a simple and rapid operation, enabling more efficient editing of the PCV2 genome. The infectious clones constructed using this method could be successfully rescued through liposome transfection, resulting in the production of recombinant viruses that could be stably passaged. Moreover, the recombinant viruses rescued by this method exhibited enhanced proliferative capacity in PK-15 cells and 3D4/31 cells (immortalized porcine alveolar macrophages). In conclusion, this study has established a novel reverse genetics system for PCV2, providing a new strategy for the development of PCV2 genetic engineering vaccines. Additionally, it serves as a reference for the construction of infectious clones for other emerging circoviruses such as PCV3 and PCV4.

Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.

Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.

Apolipoprotein D facilitates rabies virus propagation by interacting with G protein and upregulating cholesterol.

Rabies virus (RABV) causes a fatal neurological disease, consisting of unsegmented negative-strand RNA, which encodes five structural proteins (3'-N-P-M-G-L-5'). Apolipoprotein D (ApoD), a lipocalin, is upregulated in the nervous system after injury or pathological changes. Few studies have focused on the role of ApoD during virus infection so far. This study demonstrated that ApoD is upregulated in the mouse brain (in vivo) and C8-D1A cells (in vitro) after RABV infection. By upregulating ApoD expression in C8-D1A cells, we found that ApoD facilitated RABV replication. Additionally, Co-immunoprecipitation demonstrated that ApoD interacted with RABV glycoprotein (G protein). The interaction could promote RABV replication by upregulating the cholesterol level. These findings revealed a novel role of ApoD in promoting RABV replication and provided a potential therapeutic target for rabies.

Using UAV-Based Temporal Spectral Indices to Dissect Changes in the Stay-Green Trait in Wheat.

Stay-green (SG) in wheat is a beneficial trait that increases yield and stress tolerance. However, conventional phenotyping techniques limited the understanding of its genetic basis. Spectral indices (SIs) as non-destructive tools to evaluate crop temporal senescence provide an alternative strategy. Here, we applied SIs to monitor the senescence dynamics of 565 diverse wheat accessions from anthesis to maturation stages over 2 field seasons. Four SIs (normalized difference vegetation index, green normalized difference vegetation index, normalized difference red edge index, and optimized soil-adjusted vegetation index) were normalized to develop relative stay-green scores (RSGS) as the SG indicators. An RSGS-based genome-wide association study identified 47 high-confidence quantitative trait loci (QTL) harboring 3,079 single-nucleotide polymorphisms associated with SG and 1,085 corresponding candidate genes. Among them, 15 QTL overlapped or were adjacent to known SG-related QTL/genes, while the remaining QTL were novel. Notably, a set of favorable haplotypes of SG-related candidate genes such as TraesCS2A03G1081100, TracesCS6B03G0356400, and TracesCS2B03G1299500 are increasing following the Green Revolution, further validating the feasibility of the pipeline. This study provided a valuable reference for further quantitative SG and genetic research in diverse wheat panels.

Discovery of Novel PTP1B Inhibitors with Once-Weekly Therapeutic Potential for Type 2 Diabetes: Design, Synthesis, and In Vitro and In Vivo Investigations of BimBH3 Peptide Analogues.

Poor medication adherence in patients with type 2 diabetes mellitus has become one of the main causes of suboptimal glycemic control. Once-weekly drugs can markedly improve the convenience, adherence, and quality of life of T2DM patients; thus, they are clinically needed and preferred. PTP1B plays a negative role in both insulin and leptin signaling pathways, which makes it an important target for diabetes. Herein, we design and synthesize 35 analogues of core BimBH3 peptide via lipidation/acylation strategy based on our previous work and evaluate their PTP1B inhibitory activity, obtaining the primary structure-activity relationship. Five compounds with good PPT1B inhibitory activity, target selectivity, and significantly improved stability were selected for molecular docking study and searching candidate molecules with long-acting antidiabetic potential. The in vivo anti-T2DM evaluation validated the once-weekly therapeutic potential of analogues 19, 26, 27, 31, and 33, which were comparable with semaglutide and therefore presented as promising drug candidates.

Utilization of a Wheat50K SNP Microarray-Derived High-Density Genetic Map for QTL Mapping of Plant Height and Grain Traits in Wheat.

Plant height is significantly correlated with grain traits, which is a component of wheat yield. The purpose of this study is to investigate the main quantitative trait loci (QTLs) that control plant height and grain-related traits in multiple environments. In this study, we constructed a high-density genetic linkage map using the Wheat50K SNP Array to map QTLs for these traits in 198 recombinant inbred lines (RILs). The two ends of the chromosome were identified as recombination-rich areas in all chromosomes except chromosome 1B. Both the genetic map and the physical map showed a significant correlation, with a correlation coefficient between 0.63 and 0.99. However, there was almost no recombination between 1RS and 1BS. In terms of plant height, 1RS contributed to the reduction of plant height by 3.43 cm. In terms of grain length, 1RS contributed to the elongation of grain by 0.11 mm. A total of 43 QTLs were identified, including eight QTLs for plant height (PH), 11 QTLs for thousand grain weight (TGW), 15 QTLs for grain length (GL), and nine QTLs for grain width (GW), which explained 1.36-33.08% of the phenotypic variation. Seven were environment-stable QTLs, including two loci (Qph.nwafu-4B and Qph.nwafu-4D) that determined plant height. The explanation rates of phenotypic variation were 7.39-12.26% and 20.11-27.08%, respectively. One QTL, Qtgw.nwafu-4B, which influenced TGW, showed an explanation rate of 3.43-6.85% for phenotypic variation. Two co-segregating KASP markers were developed, and the physical locations corresponding to KASP_AX-109316968 and KASP_AX-109519968 were 25.888344 MB and 25.847691 MB, respectively. Qph.nwafu-4B, controlling plant height, and Qtgw.nwafu-4B, controlling TGW, had an obvious linkage relationship, with a distance of 7-8 cM. Breeding is based on molecular markers that control plant height and thousand-grain weight by selecting strains with low plant height and large grain weight. Another QTL, Qgw.nwafu-4D, which determined grain width, had an explanation rate of 3.43-6.85%. Three loci that affected grain length were Qgl.nwafu-5A, Qgl.nwafu-5D.2, and Qgl.nwafu-6B, illustrating the explanation rates of phenotypic variation as 6.72-9.59%, 5.62-7.75%, and 6.68-10.73%, respectively. Two QTL clusters were identified on chromosomes 4B and 4D.

Discovery of Novel PTP1B Inhibitors Derived from the BH3 Domain of Proapoptotic Bcl-2 Proteins with Antidiabetic Potency.

BH3 peptide analogues are generally believed to exhibit great potency as cancer therapeutics via targeting antiapoptotic Bcl-2 proteins. Here, we describe the synthesis and identification of a new class of palmitoylated peptide BH3 analogues derived from the core region (h1-h4) of BH3 domains of proapoptotic Bcl-2 proteins and as alternative PTP1B inhibitors with antidiabetic potency in vitro and in vivo. PTP1B inhibitors are attractive for treatment of type 2 diabetes. We design the analogues using a simple lipidation approach and discovered novel lead analogues with promising antidiabetic potency in vitro and in vivo. The results presented here expanded the alternative target and function for the BH3 peptide analogues from one member Bim to other members of the proapoptotic Bcl-2 proteins and emphasize their therapeutic potential in T2DM. Furthermore, our findings may provide new proof of the regulatory function of Bcl-2 family proteins in mitochondrial nutrient and energy metabolism.

Synthesis, aphicidal activity and conformation of novel insect kinin analogues as potential eco-friendly insecticides.

BACKGROUND: The discovery of ecofriendly insecticides through a new strategy for aphid control is important because of the substantial resistance and unexpected eco-toxicity to honeybees caused by traditional insecticides. The insect kinins, a class of multifunctional insect neuropeptides, are considered for potential application in pest control. In our previous work we developed several series of insect kinin analogues and found a promising lead II-1 with good aphicidal activity. To seek further eco-friendly aphicides, the optimization of II-1 is carried out in this study. RESULTS: Fifteen novel Yaa3 modified analogues based on the lead II-1 were synthesized. The aphicidal tests indicated that IV-3, IV-5 and IV-10 exhibited significant activity against the soybean aphid Aphis glycines with LC50 values of 0.0029, 0.0072 and 0.0086 mmol L-1 , respectively, higher than that of lead II-1 and the commercial Pymetrozine. The molecular modeling results showed that analogues II-1, IV-3, IV-5, IV-7 and IV-10 formed a ß-turn-like conformation, while the conformation of analogues IV-1, IV-2 and IV-9 seemed to be linear. Some structural elements favorable for the activity were proposed based on the conformation-activity relationship of the analogues. CONCLUSION: Insect kinin analogues derived from lead II-1 by modifying the hydrolysis site Yaa3 with natural, sterically hindered α- and ß-amino acids showed great potential as eco-friendly insecticides. Inspiringly, the most active analogue IV-3 can be a candidate for further development. The ß-turn-like conformation and the orientation of the aromatic rings of the side chain of Phe2 and Trp4 may be critical factors beneficial to activity. © 2019 Society of Chemical Industry.

A ß-1,3/1,6-glucan from Durvillaea Antarctica inhibits tumor progression in vivo as an immune stimulator.

ß-glucans trigger the proinflammatory responses of innate immune cells to enhance the host defense. A variety of ß-glucans were identified as strong immune stimulator and exerted antitumor activities. Our previous work indicates that a ß-1,3/1,6-glucan (BG136) derived from marina alga Durvillaea antarctica promotes the proinflammatory responses in macrophage cell line RAW264.7. In the present study, we further explored its antitumor effects in vivo as an immune stimulator. The data shows that BG136 alone decreases the tumor burdens in DLD1 xenograft and AOM-DSS induced tumor models. BG136 also augments the antitumor effects of PD-1 antibody in B16 syngeneic tumor model. BG136 increases macrophage phagocytosis, enhances cytokine/chemokine secretion and modulates the systemic and intratumoral immune cell composition. Collectively, these data suggest that BG136 might act as an immune stimulator to exert antitumor effects in vivo.

DNA methylation profile of psoriatic skins from different body locations.

Aim: To understand whether the anatomical location of origin plays a role in shaping the DNA methylation (DNAm) landscape of psoriatic skins. Patients & methods: A number of 108 psoriatic and 57 control skin samples were grouped based on their anatomical locations. Two group t-tests were used to identify those differentially methylated sites and regions. Target region methylation loci were validated by bisulfate conversion sequencing. The correlations of DNAm with pathological features, DNAm and gene expression were also interrogated. Results: Our analysis revealed 315 location-specific differentially methylated sites for back, 291 for the extremities and 801 for abdomen. Moreover, we observed that the extremity-specific loci cg21942490 located on HOXA9 is associated with hyperkeratosis. We further observed that HOXA5 and KIAA1949 are differential methylation regions. Conclusion: Our study shown evidence of anatomical location-dependent DNAm pattern in psoriasis skins, and thus provided new insights into the pathogenesis of this disease.

Synthesis of ring-contracted erythromycin A derivatives via microwave-assisted intramolecular transesterification.

The synthesis of ring-contracted derivatives of erythromycin A via intramolecular transesterification under microwave irradiation of 8,9-anhydroerythromycin A 6,9-hemiketal and its derivatives is described. It was found that microwave irradiation could significantly improve the yields and shorten the reaction times under either solvent-containing (method A) or solvent-free (method B) conditions.

Design, synthesis and aphicidal activity of N-terminal modified insect kinin analogs.

The insect kinins are a class of multifunctional insect neuropeptides present in a diverse variety of insects. Insect kinin analogs showed multiple bioactivities, especially, the aphicidal activity. To find a biostable and bioactive insecticide candidate with simplified structure, a series of N-terminal modified insect kinin analogs was designed and synthesized based on the lead compound [Aib]-Phe-Phe-[Aib]-Trp-Gly-NH2. Their aphicidal activity against the soybean aphid Aphis glycines was evaluated. The results showed that all the analogs maintained the aphicidal activity. In particular, the aphicidal activity of the pentapeptide analog X Phe-Phe-[Aib]-Trp-Gly-NH2 (LC50=0.045mmol/L) was similar to the lead compound (LC50=0.048mmol/L). This indicated that the N-terminal protective group may not play an important role in the activity and the analogs structure could be simplified to pentapeptide analogs while retaining good aphicidal activity. The core pentapeptide analog X can be used as the lead compound for further chemical modifications to discover potential insecticides.