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Plants of the Meliaceae family have long attracted researchers’ interest due to their various insecticidal activities, with triterpenes being the main active ingredients. In this paper, we discuss 93 triterpenoids with insecticidal activity from 37 insecticidal plant species of 15 genera (Munronia, Neobeguea, Pseudocedrela, Nymania, Quivisia, Ruagea, Dysoxylum, Soymida, Lansium, Sandoricum, Walsura, Trichilia, Swietenia, Turraea, and Xylocarpus) in the family Meliaceae. Among these genera, Trichilia deserves further research, with twelve species possessing insecticidal activity. The 93 insecticidal molecules included 27 ring-seco limonoids (comprising 1 ring A-seco group chemical, 1 ring B-seco group chemical, 5 ring D-seco group chemicals, 14 rings A,B-seco group chemicals, 5 rings B,D-seco group chemicals, and 1 rings A,B,D-seco group chemical), 22 ring-intact limonoids (comprising 5 cedrelone-class chemicals, 6 trichilin-class chemicals, 7 havanensin-class chemicals, 2 azadirone-class chemicals, 1 vilasinin-class chemical, and 1 other chemical), 33 2,30-linkage chemicals (comprising 25 mexicanolide-class chemicals and 8 phragmalin-class chemicals), 3 1,n-linkage-group chemicals, 3 onoceranoid-type triterpenoids, 2 apotirucallane-type terpenoids, 2 kokosanolide-type tetranortriterpenoids, and 1 cycloartane triterpene. In particular, 59 molecules showed antifeedant activity, 30 molecules exhibited poisonous effects, and 9 molecules possessed growth regulatory activity. Particularly, khayasin, beddomei lactone, 3β,24,25-trihydroxycycloartane, humilinolides A–E and methyl-2-hydroxy-3β-isobutyroxy-1-oxomeliac-8(30)-enate showed excellent insecticidal activities, which were comparable to that of azadirachtin and thus deserved more attention. Moreover, it was noteworthy that various chemicals (such as 12α-diacetoxywalsuranolide, 11β,12α-diacetoxycedrelone, 1α,7α,12α-triacetoxy-4α-carbomethoxy-11β-hydroxy-14β,15β-epoxyhavanensin, and 11-epi-21-hydroxytoonacilide, etc.) from Turraea showed excellent insecticidal activity. Specially, the insecticidal activity of khayasin from Neobeguea against the coconut leaf beetle were similar to that of rotenone. Therefore, it was a promising candidate insecticide for the control of the coconut leaf beetle.

Tetranychus urticae Koch (T. urticae) is one of the most tremendous herbivores due to its polyphagous characteristics, and is resistant to most acaricides. In this study, enzyme-linked immunosorbent assay (ELISA), transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were carried out to analyze the mechanisms of T. urticae metabolic resistance to cyflumetofen and bifenthrin on cowpea. The enzyme activity of UDP-glucuronosyltransferases (UGTs) and carboxylesterases (CarEs) in the cyflumetofen-resistant (R_cfm) strain significantly decreased, while that of cytochrome P450 monooxygenases (P450s) significantly increased. Meanwhile, the activities of glutathione-S-transferases (GSTs), CarEs and P450s in the bifenthrin-resistant (R_bft) strain were significantly higher than those in the susceptible strain (Lab_SS). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, in the R_cfm mite strain, two carboxyl/cholinesterase (CCE) genes and two P450 genes were upregulated and one gene was downregulated, namely CYP392E7; in the R_bft mite strain, eleven CCE, nine UGT, two P450, four GST and three ABC genes were upregulated, while four CCE and three P450 genes were downregulated. Additionally, 94 differentially expressed genes (DEGs) were common to the two resistant groups. Specifically, TuCCE46 and TuCCE70 were upregulated in both resistant groups. Furthermore, the qRT-PCR validation data were consistent with those from the transcriptome sequencing analysis. Specifically, TuCCE46 (3.37-fold) was significantly upregulated in the R_cfm strain, while in the R_bft strain, TeturUGT22 (5.29-fold), teturUGT58p (1.74-fold), CYP392A11 (2.89-fold) and TuGSTd15 (5.12-fold) were significantly upregulated and TuCCE01 (0.13-fold) and CYP392A2p (0.07-fold) were significantly downregulated. Our study indicates that TuCCE46 might play the most important role in resistance to cyflumetofen, and TuCCE01, teturUGT58p, teturUGT22, CYP392A11, TuGSTd15, TuGSTm09 and TuABCG-13 were prominent in the resistance to bifenthrin. These findings provide further insight into the critical genes involved in the metabolic resistance of T. urticae to cyflumetofen and bifenthrin.

The insulin receptor (IR) is a transmembrane protein that is activated by ligands in insulin signaling pathways. The IR has been considered as a novel therapeutic target for clinical intervention, considering the overexpression of its protein and A-isoform in multiple cancers, Alzheimer’s disease, and Type 2 diabetes mellitus in humans. Meanwhile, it may also serve as a potential target in pest management due to its multiple physiological influences in insects. In this review, we provide an overview of the structural and molecular biology of the IR, functions of IRs in humans and insects, physiological and nonpeptide small molecule modulators of the IR, and the regulating mechanisms of the IR. Xenobiotic compounds and the corresponding insecticidal chemicals functioning on the IR are also discussed. This review is expected to provide useful information for a better understanding of human IR-related diseases, as well as to facilitate the development of novel small-molecule activators and inhibitors of the IR for use as medicines or pesticides.

Plant-originated triterpenes are important insecticidal molecules. Research on the insecticidal activity of molecules from Meliaceae plants has always been a hotspot due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discussed 116 triterpenoid molecules with insecticidal activity from 22 plant species of five genera (Cipadessa, Entandrophragma, Guarea, Khaya, and Melia) in Meliaceae. In these genera, the insecticidal activities of plants from Entandrophragma and Melia have attracted substantial research attention in recent years. Specifically, the insecticidal activities of plants from Melia have been systemically studied for several decades. In total, the 116 insecticidal chemicals consisted of 34 ring-intact limonoids, 31 ring-seco limonoids, 48 rearranged limonoids, and 3 tetracyclic triterpenes. Furthermore, the 34 ring-intact limonoids included 29 trichilin-class chemicals, 3 azadirone-class chemicals, and 1 cedrelone-class and 1 havanensin-class limonoid. The 31 ring-seco limonoids consisted of 16 C-seco group chemicals, 8 B,D-seco group chemicals, 4 A,B-seco group chemicals, and 3 D-seco group chemicals. Furthermore, among the 48 rearranged limonoids, 46 were 2,30-linkage group chemicals and 2 were 10,11-linkage group chemicals. Specifically, the 46 chemicals belonging to the 2,30-linkage group could be subdivided into 24 mexicanolide-class chemicals and 22 phragmalin-class chemicals. Additionally, the three tetracyclic triterpenes were three protolimonoids. To sum up, 80 chemicals isolated from 19 plant species exhibited antifeedant activity toward 14 insect species; 18 chemicals isolated from 17 plant species exhibited poisonous activity toward 10 insect species; 16 chemicals isolated from 11 plant species possessed growth-regulatory activity toward 8 insect species. In particular, toosendanin was the most effective antifeedant and insect growth-regulatory agent. The antifeedant activity of toosendanin was significant. Owing to its high effect, toosendanin has been commercially applied. Three other molecules, 1,3-dicinnamoyl-11-hydroxymeliacarpin, 1-cinnamoyl-3-methacryl-11-hydroxymeliacarpin, and 1-cinnamoyl-3-acetyl-11-hydroxymeliacarpin, isolated from Meliaazedarach, exhibited a highly poisonous effect on Spodoptera littoralis; thus, they deserve further attention.

Plant-originated triterpenes are important insecticidal molecules. The research on insecticidal activity of molecules from Meliaceae plants has always received attention due to the molecules from this family showing a variety of insecticidal activities with diverse mechanisms of action. In this paper, we discuss 102 triterpenoid molecules with insecticidal activity of plants of eight genera (Aglaia, Aphanamixis, Azadirachta, Cabralea, Carapa, Cedrela, Chisocheton, and Chukrasia) in Meliaceae. In total, 19 insecticidal plant species are presented. Among these species, Azadirachta indica A. Juss is the most well-known insecticidal plant and azadirachtin is the active molecule most widely recognized and highly effective botanical insecticide. However, it is noteworthy that six species from Cedrela were reported to show insecticidal activity and deserve future study. In this paper, a total of 102 insecticidal molecules are summarized, including 96 nortriterpenes, 4 tetracyclic triterpenes, and 2 pentacyclic triterpenes. Results showed antifeedant activity, growth inhibition activity, poisonous activity, or other activities. Among them, 43 molecules from 15 plant species showed antifeedant activity against 16 insect species, 49 molecules from 14 plant species exhibited poisonous activity on 10 insect species, and 19 molecules from 11 plant species possessed growth regulatory activity on 12 insect species. Among these molecules, azadirachtins were found to be the most successful botanical insecticides. Still, other molecules possessed more than one type of obvious activity, including 7-deacetylgedunin, salannin, gedunin, azadirone, salannol, azadiradione, and methyl angolensate. Most of these molecules are only in the primary stage of study activity; their mechanism of action and structure–activity relationship warrant further study.

Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects.

It is well known that cyclin B3 (cycB3) plays a key role in the control of cell cycle progression. However, whether cycB3 is involved in stem cell fate determination remains unknown. The Drosophila ovary provides an exclusive model for studying the intrinsic and extrinsic factors that modulate the fate of germline stem cells (GSCs). Here, using this model, we show that Drosophila cycB3 plays a new role in controlling the fate of germline stem cells (GSC). Results from cycB3 genetic analyses demonstrate that cycB3 is intrinsically required for GSC maintenance. Results from green fluorescent protein (GFP)-transgene reporter assays show that cycB3 is not involved in Dad-mediated regulation of Bmp signaling, or required for dpp-induced bam transcriptional silencing. Double mutants of bam and cycB3 phenocopied bam single mutants, suggesting that cycB3 functions in a bam-dependent manner in GSCs. Deficiency of cycB3 fails to cause apoptosis in GSCs or influence cystoblast (CB) differentiation into oocytes. Furthermore, overexpression of cycB3 dramatically increases the CB number in Drosophila ovaries, suggesting that an excess of cycB3 function delays CB differentiation. Given that the cycB3 gene is evolutionarily conserved, from insects to humans, cycB3 may also be involved in controlling the fate of GSCs in humans.