Clinical experience sharing on gastric microneuroendocrine tumors: A case report.

BACKGROUND: The majority of gastric neuroendocrine tumors (G-NENs) are present in various lesions under endoscopy, and they can be polypoid uplifts, submucosal tumors or papules, erosions, and ulcers. The lesions are mostly confined to the mucosal or submucosal layer, usually less than 2 cm, and exclusively localized to the gastric body or fundus. In type 1 G-NENs, about 22% of cases have no visible lesions under an endoscope, and such lesions can only be detected via biopsies (microcarcinoids). CASE SUMMARY: A 67-year-old female patient with appetite loss for more than half a year and personal history of hyperthyroidism was admitted to our hospital. After admission, a random multi-point biopsy was performed on the gastric body, fundus, angle, and antrum through gastroscopy. Pathological examination showed chronic severe atrophic gastritis in the fundus and body of the stomach. The small curvature of the gastric body, the anterior wall of the gastric body, and the posterior wall of the gastric body displayed proliferation of intestinal chromaffin cells. The curvature of the gastric body showed neuroendocrine tumor G1 (carcinoid), while the antrum and angle of the stomach showed mild atrophic gastritis with mild intestinal metaplasia. Immunohistochemical examination showed that the greater curvature of the gastric body was Syn (+), CgA (+), and Ki-67 (+, approximately 1%), which is consistent with neuroendocrine tumors (grade 1). Regular gastroscopy and biopsy should be performed every one to two years to monitor G-NENs. CONCLUSION: In the case under study, the patient did not have any visible raised lesions under a gastroscope, and the lesions were found only after a random biopsy. This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

Biomineralization Process of CaCO3 Precipitation Induced by Bacillus mucilaginous and Its Potential Application in Microbial Self-healing Concrete.

Microbial induced calcium carbonate precipitation (MICP) is widely common in nature, which belongs to biomineralization and has been explored carefully in recent decades. The paper studied the effect of temperature, initial pH value and Ca2+ concentration on bacterial growth and carbonic anhydrase activity, and then revealed the biomineralization process through the changes of Ca2+ concentration and calcification rate in alkali environment. Meanwhile, microbial healing agent containing spores and calcium nitrate was prepared and used for the early age concrete cracks repair. The self-healing efficiency was assessed by crack closure rate and water permeability repair rate. The experimental results showed that when the optimal temperature was 30 °C, the pH was 8.0-11.0, and the optimal Ca2+ concentration was 0-90 mM, the bacteria could grow better and the carbonic anhydrase activity was higher. Compared with reference, the crack closure rate with the crack width up to 0.339 mm could reach 95.62% and the water permeability repair rate was 87.54% after 28 d healing time of dry-wet cycles. XRD analysis showed that the precipitates at the crack mouth were calcite CaCO3. Meanwhile, the self-healing mechanism of mortar cracks was discussed in detail. In particular, there is no other pollution in the whole mineralization process, and the self-healing system is environmentally friendly, which provides a novel idea and method for the application of microbial self-healing concrete.

Myosin VI stabilizes intercellular junctions in the testis through the LHR and MAPK signalling pathway during spermatogenesis in Eriocheir sinensis.

The myosin motor protein myosin VI plays an essential role in mammalian spermatogenesis, however, the effects of myosin VI on male reproduction in Crustacea remain obscure. We identified the macromolecule es-Myosin VI in Eriocheir sinensis, and studied it by multiple methods. It co-localized with F-actin and was highly expressed in the testis. We interfered es-Myosin VI using dsRNA in vivo, an apparent decrease in spermatozoa count was detected. We also found that the MAPK signalling pathway was changed, subsequently causing disruption of intercellular junctions and damage to the functional hemolymph-testis barrier. We observed that luteinizing hormone receptor es-LHR was located within seminiferous tubules, which was different from the expression in mammals. Es-LHR could bind with es-Myosin VI in testis of E. sinensis, its localization was significantly altered when es-Myosin VI was deleted. Moreover, we obtained consistent results for the MAPK signalling pathway and spermatogenesis defects between the es-LHR and es-Myosin VI knockdown groups. In summary, our research demonstrated that knockdown of es-Myosin VI disturbed the intercellular junction and HTB function via the MAPK signalling pathway by changing the localization of es-LHR in the testis of E. sinensis, which was the potential reason for its negative impact on spermatogenesis.

TiO2 nanoparticles affect spermatogenesis and adhesion junctions via the ROS-mediated mTOR signalling pathway in Eriocheir sinensis testes.

Recent findings found that TiO2 nanoparticles (TiO2-NPs) have male reproductive toxicity. However, few reports have studied the toxicity of TiO2-NPs in crustaceans. In this study, we first chose the freshwater crustacean Eriocheir sinensis (E. sinensis) to explore the male toxicity of TiO2-NP exposure and the underlying mechanisms. Three nm and 25 nm TiO2-NPs at a dose of 30 mg/kg bw induced apoptosis and damaged the integrity of the haemolymph-testis-barrier (HTB, a structure similar to the blood-testis-barrier) and the structure of the seminiferous tubule. The 3-nm TiO2-NPs caused more severe spermatogenesis dysfunction than the 25-nm TiO2-NPs. We initially confirmed that TiO2-NP exposure affected the expression patterns of adherens junctions (α-catenin and ß-catenin) and induced tubulin disorganization in the testis of E. sinensis. TiO2-NP exposure caused reactive oxygen species (ROS) generation and an imbalance of mTORC1-mTORC2 (mTORC1/rps6/Akt levels were increased, while mTORC2 activity was not changed). After using the ROS scavenger NAC to inhibit ROS generation, both the mTORC1-mTORC2 imbalance and alterations in AJs were rescued. More importantly, the mTORC1 inhibitor rapamycin abolished mTORC1/rps6/Akt hyperactivation and partially restored the alterations in AJs and tubulin. Collectively, the mTORC1-mTORC2 imbalance induced by TiO2-NPs was involved in the mechanism of AJ and HTB disruption, resulting in spermatogenesis in E. sinensis.

mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis.

Mammalian target of rapamycin (mTOR) is a crucial signaling protein regulating a range of cellular events. Numerous studies have reported that the mTOR pathway is related to spermatogenesis in mammals. However, its functions and underlying mechanisms in crustaceans remain largely unknown. mTOR exists as two multimeric functional complexes termed mTOR complex 1 (mTORC1) and mTORC2. Herein, we first cloned ribosomal protein S6 (rpS6, a downstream molecule of mTORC1) and protein kinase C (PKC, a downstream effector of mTORC2) from the testis of Eriocheir sinensis. The dynamic localization of rpS6 and PKC suggested that both proteins may be essential for spermatogenesis. rpS6/PKC knockdown and Torin1 treatment led to defects in spermatogenesis, including germ cell loss, retention of mature sperm and empty lumen formation. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was disrupted in the rpS6/PKC knockdown and Torin1 treatment groups, accompanied by changing in expression and distribution of junction proteins. Further study demonstrated that these findings may result from the disorganization of filamentous actin (F-actin) networks, which were mediated by the expression of actin-related protein 3 (Arp3) rather than epidermal growth factor receptor pathway substrate 8 (Eps8). In summary, our study illustrated that mTORC1/rpS6 and mTORC2/PKC regulated spermatogenesis via Arp3-mediated actin microfilament organization in E. sinensis.

Es-ß-CATENIN affects the hemolymph-testes barrier in Eriocheir sinensis by disrupting cell junctions and cytoskeleton.

ß-CATENIN is an evolutionarily conserved multifunctional molecule that maintains cell adhesion as a cell junction protein to safeguard the integrity of the mammalian blood-testes barrier, and also regulates cell proliferation and apoptosis as a key signaling molecule in the WNT/ß-CATENIN signaling pathway. In the crustacean Eriocheir sinensis, Es-ß-CATENIN has been shown to be involved in spermatogenesis, but the testes of E. sinensis have large and well-defined structural differences from those of mammals, and the impact of Es-ß-CATENIN in them is still unknown. In the present study, we found that Es-ß-CATENIN, Es-α-CATENIN and Es-ZO-1 interact differently in the testes of the crab compared to mammals. In addition, defective Es-ß-CATENIN resulted in increased Es-α-CATENIN protein expression levels, distorted and deformed F-ACTIN, and disturbed localization of Es-α-CATENIN and Es-ZO-1, leading to loss of hemolymph-testes barrier integrity and impaired sperm release. In addition to this, we also performed the first molecular cloning and bioinformatics analysis of Es-AXIN in the WNT/ß-CATENIN pathway to exclude the effect of the WNT/ß-CATENIN pathway on the cytoskeleton. In conclusion, Es-ß-CATENIN participates in maintaining the hemolymph-testes barrier in the spermatogenesis of E. sinensis.

The N-terminal extension of Arabidopsis ARGONAUTE 1 is essential for microRNA activities.

microRNAs (miRNAs) regulate target gene expression through their ARGONAUTE (AGO) effector protein, mainly AGO1 in Arabidopsis thaliana. In addition to the highly conserved N, PAZ, MID and PIWI domains with known roles in RNA silencing, AGO1 contains a long, unstructured N-terminal extension (NTE) of little-known function. Here, we show that the NTE is indispensable for the functions of Arabidopsis AGO1, as a lack of the NTE leads to seedling lethality. Within the NTE, the region containing amino acids (a.a.) 91 to 189 is essential for rescuing an ago1 null mutant. Through global analyses of small RNAs, AGO1-associated small RNAs, and miRNA target gene expression, we show that the region containing a.a. 91-189 is required for the loading of miRNAs into AGO1. Moreover, we show that reduced nuclear partitioning of AGO1 did not affect its profiles of miRNA and ta-siRNA association. Furthermore, we show that the 1-to-90a.a. and 91-to-189a.a. regions of the NTE redundantly promote the activities of AGO1 in the biogenesis of trans-acting siRNAs. Together, we report novel roles of the NTE of Arabidopsis AGO1.

es-Arp3 and es-Eps8 regulate spermatogenesis via microfilaments in the seminiferous tubule of Eriocheir sinensis.

Spermatogenesis is a complicated process that includes spermatogonia differentiation, spermatocytes meiosis, spermatids spermiogenesis and final release of spermatozoa. Actin-related protein 3 (Arp3) and epidermal growth factor receptor pathway substrate 8 (Eps8) are two actin binding proteins that regulate cell adhesion in seminiferous tubules during mammalian spermatogenesis. However, the functions of these two proteins during spermatogenesis in nonmammalian species, especially Crustacea, are still unknown. Here, we cloned es-Arp3 and es-Eps8 from the testis of Chinese mitten crab Eriocheir sinensis. es-Arp3 and es-Eps8 were located in spermatocytes, spermatids and spermatozoa. Knockdown of es-Arp3 and es-Eps8 in vivo caused morphological changes to seminiferous tubules including delayed spermatozoa release, shedding of germ cells and vacuoles. Filamentous-actin (F-actin) filaments network was disorganized due to deficiency of es-Arp3 and es-Eps8. Accompanying this, four junctional proteins (α-catenin, ß-catenin, pinin and ZO1) displayed abnormal expression levels as well as penetrating biotin signals in seminiferous tubules. We also used the Arp2/3 complex inhibitor CK666 to block es-Arp3 activity and supported es-Arp3 knockdown results. In summary, our study demonstrated for the first time that es-Arp3 and es-Eps8 are important for spermatogenesis via regulating microfilament-mediated cell adhesion in Eriocheir sinensis.

Optical diagnostic imaging and therapy for thyroid cancer.

Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and 131I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging's promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.

Customer's Channel Selection Behavior on Purchasing Standardized and Customized Products: Optimized Prices and Channel Performances.

Nowadays, the traditional production is unable to meet the new diverse needs of target customers. In the current customization era, more and more companies are required by customers to provide more desirable customized products. However, research on customization and standardization based on quantitative analysis has drawn little attention in the literature of dual channel supply chain. In this paper, we study the effect of adopting a dual channel supply chain on the performance of a two-level system (manufacturer-retailer) by using a novelty quantitative approach. We try to analyze the system to get optimal prices and maximize profits, where manufactures offer both standardized and customized products via their traditional and customized channels, respectively. We build a Stackelberg game mode to construct a centralized and a decentralized dual channel scenarios. Furthermore, we study the effects of the different channel structures on price, degree of customization, degree of standardization, and supply chain profitability. We also analyze the effects of both standardized and customized demand sensitivities on their prices and profits. Eventually, we introduce a cost-sharing coordinating contract to optimize the channel's performance. We find that the potential market demand for customization affects the price of customized products and the profits of customized channels. Compared with the decentralized dual channel case, the cost-sharing contract can achieve higher total channel profits. In the cost-coordination case, there is an optimal range for the proportion of standardized costs borne by manufacturers.

mTORC1/C2 regulate spermatogenesis in Eriocheir sinensis via alterations in the actin filament network and cell junctions.

Spermatogenesis is a finely regulated process of germ cell proliferation and differentiation that leads to the production of sperm in seminiferous tubules. Although the mammalian target of rapamycin (mTOR) signaling pathway is crucial for spermatogenesis in mammals, its functions and molecular mechanisms in spermatogenesis remain largely unknown in nonmammalian species, particularly in Crustacea. In this study, we first identified es-Raptor (the core component of mTOR complex 1) and es-Rictor (the core component of mTOR complex 2) from the testis of Eriocheir sinensis. Dynamic localization of es-Raptor and es-Rictor implied that these proteins were indispensable for the spermatogenesis of E. sinensis. Furthermore, es-Raptor and es-Rictor knockdown results showed that the mature sperm failed to be released, causing almost empty lumens in the testis. We investigated the reasons for these effects and found that the actin-based cytoskeleton was disrupted in the knockdown groups. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was impaired and affected the expression of cell junction proteins. Further study revealed that es-Raptor and es-Rictor may regulate spermatogenesis via both mTORC1- and mTORC2-dependent mechanisms that involve es-rpS6 and es-Akt/es-PKC, respectively. Moreover, to explore the testis barrier in E. sinensis, we established a cadmium chloride (CdCl2)-induced testis barrier damage model as a positive control. Morphological and immunofluorescence results were similar to those of the es-Raptor and es-Rictor knockdown groups. Altogether, es-Raptor and es-Rictor were important for spermatogenesis through maintenance of the actin filament network and cell junctions in E. sinensis.

Follicle-stimulating hormone signaling in Sertoli cells: a licence to the early stages of spermatogenesis.

Follicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively expressed in Sertoli cells. As the only type of somatic cell in the seminiferous tubule, Sertoli cells regulate spermatogenesis not only by controlling their own number and function but also through paracrine actions to nourish germ cells surrounded by Sertoli cells. After follicle-stimulating hormone binds to its receptor and activates the follicle-stimulating hormone signaling pathway, follicle-stimulating hormone signaling will establish a normal Sertoli cell number and promote their differentiation. Spermatogonia pool maintenance, spermatogonia differentiation and their entry into meiosis are also positively regulated by follicle-stimulating hormone signaling. In addition, follicle-stimulating hormone signaling regulates germ cell survival and limits their apoptosis. Our review summarizes the aforementioned functions of follicle-stimulating hormone signaling in Sertoli cells. We also describe the clinical potential of follicle-stimulating hormone treatment in male patients with infertility. Furthermore, our review may be helpful for developing better therapies for treating patients with dysfunctional follicle-stimulating hormone signaling in Sertoli cells.

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.

In vivo two-dimensional quantitative imaging of skin and cutaneous microcirculation with perturbative spatial frequency domain imaging (p-SFDI).

We introduce perturbative spatial frequency domain imaging (p-SFDI) for fast two-dimensional (2D) mapping of the optical properties and physiological characteristics of skin and cutaneous microcirculation using spatially modulated visible light. Compared to the traditional methods for recovering 2D maps through a pixel-by-pixel inversion, p-SFDI significantly shortens parameter retrieval time, largely avoids the random fitting errors caused by measurement noise, and enhances the image reconstruction quality. The efficacy of p-SFDI is demonstrated by in vivo imaging forearm of one healthy subject, recovering the 2D spatial distribution of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, the melanin content, and the epidermal thickness over a large field of view. Furthermore, the temporal and spatial variations in physiological parameters under the forearm reactive hyperemia protocol are revealed, showing its applications in monitoring temporal and spatial dynamics.

The Native Dietary Habits of the Two Sympatric Bee Species and Their Effects on Shaping Midgut Microorganisms.

The intestinal microbial community composition of different bee species typically has host specificity, yet little is known about the underlying formation mechanism. There are signs that dietary habits vary in different bee species, suggesting that there may be close relationships between dietary habits and intestinal microorganisms. We explored this hypothesis by comparing the dietary habits and gut microbiota of two common bee species (Apis mellifera L. and Apis cerana cerana) in China. Bee bread and midgut samples from wild and laboratory-reared bees were collected, and the differences in intestinal microbial community composition and growth and development before and after the change in dietary habits of different bee species were compared. We found that the two sympatric species had different dietary specializations and similar metagenomic diversities. The microbiota composition differed between the two species. Moreover, we revealed that changes in native dietary habits destroyed the intestinal microbiota community composition, negatively affecting the growth and development of honeybees.

The dietary arachidonic acid improved growth and immunity of honey bee (Apis mellifera ligustica).

Honeybees cannot synthesize arachidonic acid (ARA) themselves, only obtain it from food. Most pollen is deficient or contains a small amount of ARA. The necessity of supplementary ARA in bees' diet has not been studied. The objective of this study was to investigate the effects of dietary ARA levels on the growth and immunity of Apis mellifera ligustica. A total of 25 honeybee colonies were randomly assigned to five dietary groups which were fed basic diets supplemented with 0, 2, 4, 6, and 8% of ARA. The diet with 4% ARA improved the body weight of newly emerged worker bees compared with the control group. Supplement of ARA in honeybee diets changed the fatty acid composition of honeybee body. SFA and MUFA contents of bees' body declined, and PUFA content rised in the ARA group. Compared with the control group, the supplement of ARA in honeybee diets increased the contents of ARA, C22:6n-3 (DHA) and C18:3n-6 in bees' body significantly, but decreased the contents of C16:1 and C18:3n-3. The diet supplied with 4% ARA reduced the mortality rate of honeybee infected with Escherichia coli. The activity of immune enzymes (phenoloxidase, antitrypsin, and lysozyme) and the mRNA expression levels of immune genes (defensin-2, toll, myd88, and dorsal) were improved by ARA diets to varying degrees depending on the ARA levels, especially 4% ARA. These results suggested that dietary ARA could improve the growth, survival, and immune functions of honeybees. Supplement of ARA in bees' diet would be valuable for the fitness of honeybees.

Over-immunity mediated abnormal deposition of lignin arrests the normal enlargement of the root tubers of Rehmannia glutinosa under consecutive monoculture stress.

The rapid accumulation of lignin in the cell wall is one of important immune defense mechanism in response to adversity stress in plants. In this study, we found that the enlargement of the root tubers of Rehmannia glutinosa (R. glutinosa) is arrested under consecutive monoculture stress, and this process is accompanied by abnormal accumulation of lignin. Meanwhile, the function of key catalytic enzyme genes in lignin biosynthetic pathway under consecutive monoculture stress was systematically analyzed, of which roles of core genes were validated using reverse genetics. We elucidated that an abnormal deposition of lignin in R. glutinosa roots, induced by consecutive monoculture stress, and arrested the enlargement of root tubers. Additionally, by manipulating the key catalytic enzyme gene RgCCR6, we were able to alter lignin content of roots of R. glutinosa, thereby affecting tuber enlargement. We speculate that cell lignification is an important defense strategy in resistance against consecutive monoculture stress, but the overreacted defense hindered the normal enlargement of root tubers. The findings provide new insights for effectively improving yield reductions of root crops subjected to environmental stress.

Control of Panama disease of banana by intercropping with Chinese chive (Allium tuberosum Rottler): cultivar differences.

Panama disease (Fusarium wilt disease) caused by Fusarium oxysporum f. sp. cubense race 4 (FOC) severely threatens banana (Musa spp.) production worldwide. Intercropping of banana with Allium plants has shown a potential to reduce Panama disease. In this study, six cultivars of Chinese chive (Allium tuberosum Rottler) were selected to compare their differences in antifungal activity and active compounds. Three cultivars Duokang Fujiu 11, Fujiuhuang 2, and Duokang Sijiqing with higher levels of antifungal compounds were further used for intercropping with banana in the pots and field to compare their effects on growth and disease incidence of banana.The six cultivars showed significant differences in antifungal activity against FOC mycelia growth in both leaf volatiles and aqueous leachates. The aqueous leachates displayed stronger antifungal activity than the volatiles. FJH cultivar showed the best inhibitory effect among all six cultivars. Contents of three main antifungal compounds dipropyl trisulfide (DPT), dimethyl trisulfide (DMT), and 2-methyl-2-pentenal (MP) in volatiles and aqueous leachates varied considerably among cultivars. Pot and field experiments showed that intercropping with three selected Chinese chive cultivars significantly improved banana vegetative growth, increased photosynthetic characteristics and yield but decreased disease incidence of Panama disease.Our results indicate that intercropping with Chinese chive shows potential to reduce banana Panama disease and selection of appropriate cultivars is vital for effective disease control.

Activiation of the nitric oxide cycle by citrulline and arginine restores susceptibility of resistant brown planthoppers to the insecticide imidacloprid.

Pest management, which is critical for global crop productivity, is hampered by rapidly evolving insecticide resistance in insect pests. The ability to manage the development of insecticide resistance is thus vital. Nitric oxide (NO) is a ubiquitous signaling molecule with important functions in a variety of biological processes. Here we show that imidacloprid-resistant brown planthoppers (BPH) are deficient in citrulline and arginine, both of which are involved in NO production, but exogenous citrulline and arginine render resistant BPH vulnerable to imidacloprid. BPH insecticide resistance results from low NO production; exogenous arginine and citrulline augment the NO signaling in BPH, leading to downregulation of CYP6AY1 and CYP6ER1, the cytochrome P450 s that contribute to imidacloprid detoxification, thereby restoring susceptibility. Two amino acids that can be used to restore susceptibility in insecticide-resistant insects are identified, establishing a novel metabolome-based approach for killing insecticide-resistant pests and providing a useful template for managing insecticide resistance.