KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Iodine-Catalyzed Cyclization of o-Nitrothiophenols with Cyclohexanones to Phenothiazines.

Here, a novel iodine-catalyzed direct cyclization of o-nitrothiophenols with cyclohexanones to phenothiazines has been described without external oxidants and hydrogen acceptors. The nitro of o-nitrothiophenol works as both a hydrogen acceptor and a coupling group, and water is the only byproduct. The reaction involves the reduction of nitro groups, C-H bond thioetherification, and C-H bond dehydroaromatization. This scheme offers broad synthetic value for further elaborations, as exemplified by a 3-step total synthesis of antipsychotic chlorpromazine.

[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

Direct Synthesis of Esters from Alkylarenes and Carboxylic Acids: The C-H Bond Dehydroesterification.

Herein, a reaction in which the benzyl C-H bonds of alkylarenes are directly esterified by carboxylic acids to produce benzyl esters in high yields is reported. This reaction is catalyzed by Pd nanoparticles (NPs) on N-doped carbon (CN) composites based on a carbonizing Al-MIL-101(NH2) material, and no oxidants or hydrogen acceptors are required. Use of o-alkylbenzoic acids as substrates leads to phthalides, whereas with carboxylic acids and alkylarenes as the feedstock, the reaction produces the benzyl esters. These reactions that use readily available alkylarenes instead of benzyl halides or benzyl alcohols as raw materials for one-step synthesis of benzyl esters without oxidants are inherently atom- and step-efficient. The CN composites and the CN-supported Pd NP catalysts were prepared and are well characterized. The proposed mechanism involves dehydrogenation of both the carboxylic groups and the benzylic groups and the transformation of benzylic C-H bond into the C-O bond via hydrogen abstraction from the benzylic group through an organopalladium intermediate. The kinetic isotope effect (kH/kD = 2.77) indicated that C(sp3)-H bond cleavage of the alkane aromatics is the rate-determining step.

Insights into multidimensional transport flux from vertical observation and numerical simulation in two cities in North China.

This study represents the first quantitative evaluation of pollution transport budget within the boundary layer of typical cities in the Beijing-Tianjin-Hebei (BTH) region from the perspective of horizontal and vertical exchanges and further discusses the impact of the atmospheric boundary layer (ABL)-free troposphere (FT) exchange on concentration of fine particulate matter (PM2.5) within the ABL during heavy pollution. From the perspective of the transport flux balance relationship, differences in pollution transport characteristics between the two cities is mainly reflected in the ABL-FT exchange effect. The FT mainly flowed into the ABL in BJ, while in SJZ, the outflow from the ABL to the FT was more intense. Combined with an analysis of vertical wind profile distribution, BJ was found to be more susceptible to the influence of northwest cold high prevailing in winter, while sinking of strong cold air allowed the FT flowing into the ABL influence the vertical exchange over BJ. In addition, we selected a typical pollution event for targeted analysis to understand mechanistic details of the influence of ABL-FT exchange on the pollution event. These results showed that ABL-FT interaction played an important role in PM2.5 concentration within the ABL during heavy pollution. Especially in the early stage of heavy pollution, FT transport contributed as much as 82.74% of PM2.5 within the ABL. These findings are significant for improving our understanding of pollution transport characteristics within the boundary layer and the effect of ABL-FT exchange on air quality.

A review of the technology and applications of methods for evaluating the transport of air pollutants.

A variety of methods based on air quality models, including tracer methods, the brute-force method (BFM), decoupled direct method (DDM), high-order decoupled direct method (HDDM), response surface models (RSMs) and so on forth, have been widely used to study the transport of air pollutants. These methods have good applicability for the transport of air pollutants with simple formation mechanisms. However, differences in research conclusions on secondary pollutants with obvious nonlinear characteristics have been reported. For example, the tracer method is suitable for the study of simplified scenarios, while HDDM and RSMs are more suitable for the study for nonlinear pollutants. Multiple observation techniques, including conventional air pollutant observation, lidar observation, air sounding balloons, vehicle-mounted and ship-borne technology, aerial surveys, and remote sensing observations, have been utilized to investigate air pollutant transport characteristics with time resolution as high as 1 sec. In addition, based on a multi-regional input-output model combined with emission inventories, the transfer of air pollutant emissions can be evaluated and applied to study the air pollutant transport characteristics. Observational technologies have advantages in temporal resolution and accuracy, while modeling technologies are more flexible in spatial resolution and research plan setting. In order to accurately quantify the transport characteristics of pollutants, it is necessary to develop a research method for interactive verification of observation and simulation. Quantitative evaluation of the transport of air pollutants from different angles can provide a scientific basis for regional joint prevention and control.

The post-translational modification of Fascin: impact on cell biology and its associations with inhibiting tumor metastasis.

The post-translational modifications (PTMs), which are crucial in the regulation of protein functions, have great potential as biomarkers of cancer status. Fascin (Fascin actin-bundling protein 1, FSCN1), a key protein in the formation of filopodia that is structurally based on actin filaments (F-actin), is significantly associated with tumor invasion and metastasis. Studies have revealed various regulatory mechanisms of human Fascin, including PTMs. Although a number of Fascin PTM sites have been identified, their exact functions and clinical significance are much less explored. This review explores studies on the functions of Fascin and briefly discusses the regulatory mechanisms of Fascin. Next, to review the role of Fascin PTMs in cell biology and their associations with metastatic disease, we discuss the advances in the characterization of Fascin PTMs, including phosphorylation, ubiquitination, sumoylation, and acetylation, and the main regulatory mechanisms are discussed. Fascin PTMs may be potential targets for therapy for metastatic disease.

Brain Connectivity, and Hormonal and Behavioral Correlates of Sustained Weight Loss in Obese Patients after Laparoscopic Sleeve Gastrectomy.

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.

Chemical characteristics and regional transport of submicron particulate matter at a suburban site near Lanzhou, China.

Lanzhou, which is a valley city on the Loess Plateau, frequently suffered from aerosol pollution in recent years, especially in winter. However, the lack of understanding of factors governing aerosol pollution limits the implementation of effective emission policies in and around Lanzhou. To help solve this problem, an intensive field campaign was conducted at the SACOL site, which is a suburban site near Lanzhou, in winter 2018. The chemical characteristics and sources of submicron particulate matter (PM1) were investigated, and the influence of the topography around Lanzhou on aerosol pollution was examined. In the present study, the average PM1 mass concentration reached 25.6 ± 12.8 µg m-3, with 41.0% organics, 16.1% sulfate, 19.7% nitrate, 10.7% ammonium, 3.1% chloride, and 9.4% black carbon (BC). Three organic aerosol (OA) factors were identified with the positive matrix factorization (PMF) algorithm, including a biomass burning OA (BBOA, 13.6%), a coal combustion OA (CCOA, 34.2%), and an oxygenated OA (OOA, 52.2%). The significant relationships between organics, BC, and chloride and wind pattern suggested that the SACOL site was strongly influenced by regionally transported aerosols. Further analysis suggested that these aerosol regional transport events were caused by topography. Due to the limitation of the valley, aerosols accumulated in the valley. These accumulated aerosols were then transported to the SACOL site along the valley by prevailing winds. Our study highlights enhanced aerosol regional transport in valleys, which provides a new perspective for future studies on aerosol pollution in basins and valleys.

Chlorogenic acid intake guidance: Sources, health benefits, and safety.

Chlorogenic acid (CGA) is widely present in plant foods and has attracted much attention due to biological activities such as those which are antioxidant, anti-inflammatory, antibacterial, and antiviral. It plays a role in regulating glucose and lipid metabolism, improving insulin resistance, and reducing the risk of type 2 diabetes and cardiovascular diseases. The estimated dietary intake of CGA is 5 to 1000 mg/d. Based on the data from population intervention studies, daily oral doses of CGA at 13.5mg to 1200 mg can reduce fasting blood glucose (FBG), improve glucose tolerance, enable weight loss /prevent weight gain, and improve blood pressure in hypertensive patients. Daily intake of 200 mg or more may reduce FBG, with a dose-effect relationship in the range 13.5-500 mg/d. Therefore, a specific proposed level (SPL) of CGA to improve FBG could be ≥200 mg/d. Data insufficiency does not allow formulation of a tolerable upper intake level (TUIL) for CGA.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.

Role of forkhead box gene family in bone metabolism.

Bone metabolism is associated with many bone diseases and regulated by multiple signal pathways. Over the past three decades, the functions of a superfamily of evolutionarily conserved transcriptional regulators, known as forkhead box (Fox) family, has been demonstrated to contribute to the bone metabolism. Genetic analysis studies have demonstrated that Fox gene family participate in bone metabolism and that their expression can be regulated by multiple factors. The deregulation of Fox gene family can lead to a series of bone metabolic diseases. In this manuscript, we sketched the biology of the Foxs family, summarized its function of regulating bone metabolism and maintaining bone homeostasis to estimate its potential therapeutic effects in bone diseases, and suggested directions for future exploration in this important field.

Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients.

This study was designed to investigate the metabolic and transcriptional alterations in seminal fluid caused by asthenozoospermia (AS). To address these issues, a method of metabonomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and real-time quantitative PCR (RT-qPCR) was performed to identify some crucial biomarkers and transcription levels of the enzymes in seminal fluid. Seminal fluid samples were collected from 87 AS patients and 73 healthy males with normozoospermia. The quantitative analysis by UPLC-MS/MS showed that 19 metabolites in seminal plasma were associated with AS, and they were involved in several metabolic pathways, such as energy metabolism, purine metabolism, methionine cycle, and branched chain amino acid metabolism. Among these metabolites, the levels of citric acid, malic acid, succinic acid, and pyruvic acid, which are related to energy metabolism, were collectively reduced in the AS group, whereas the lactic acid level was enhanced. These results indicated that lesser energy source (adenosine triphosphate) was produced through the anaerobic glycolysis pathway rather than via aerobic catabolism of suger and tricarboxylic acid cycle, resulting in reduced power of sperms. Meanwhile, partial least squares discriminant analysis showed significant differences in metabolic profiles between the AS and control groups. In addition, RT-qPCR results revealed that the expression levels of four genes encoding fructokinase citrate synthase, succinate dehydrogenase, and spermine synthase, which were related to energy metabolism, were decreased in the AS group. The 23 descriptors with differential expression in AS may be valuable for the diagnosis and sequential study on AS. These results will help highlight the role of sperm inactivity in AS pathogenesis.

TGFß-induced factor homeobox 2 blocks osteoblastic differentiation through targeting pSmad3/HDAC4/H4ac/Runx2 axis.

TGFß-induced factor homeobox 2 (Tgif2) has been reported as a functional role in cell homeostasis and a key activator of osteoclastogenesis and bone loss, as well. In the present study, we aimed to investigate the potential role of Tgif2 on osteogenic differentiation. Tgif2 expression was assessed during the osteogenic differentiation process of bone marrow-derived mesenchymal stem cells (BMSCs) and primary calvarial osteoblasts (OBs). The expression of Tgif2 in BMSCs and OBs increased by using lentivirus-mediated gene overexpression (OE). The effect of Tgif2 on osteogenic differentiation was compared between Tgif2 negative control (Tgif2-NC) and Tgif2-OE group in BMSCs/OBs via performing alkaline phosphatase (ALP) assay, mineralization assay, and gene expression analysis of some osteogenic markers. To investigate the molecular mechanism, the direct interaction of histone deacetylase 4 (HDAC4) and pSmad3, acetylated histone H4 (H4ac), and Runx2-binding site of the Ocn promoter was confirmed by performing co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assay, respectively. The results showed that Tgif2 abundantly expressed in BMSCs and primary calvarial OBs, but decreased after osteogenic induction. In vitro, osteogenic differentiation was significantly inhibited with Tgif2 overexpression in both BMSCs and OBs, as well as the expression levels of osteogenic markers (Runx2, Sp7, Alp, and Ocn). Moreover, we found that Tgif2 overexpression significantly promoted the interaction of pSmad3 with HDAC4 in differentiated OBs, and sequentially decreased the abundance of H4ac at the Runx2-binding site of the Ocn promoter. These findings indicated that Tgif2 might block osteoblastic differentiation in vitro through targeting pSmad3/HDAC4/H4ac/Runx2 axis.

Autophagy as a target for glucocorticoid-induced osteoporosis therapy.

Autophagy takes part in regulating the eukaryotic cells function and the progression of numerous diseases, but its clinical utility has not been fully developed yet. Recently, mounting evidences highlight an important correlation between autophagy and bone homeostasis, mediated by osteoclasts, osteocytes, bone marrow mesenchymal stem cells, and osteoblasts, and autophagy plays a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The combinations of autophagy activators/inhibitors with anti-GIOP first-line drugs or some new autophagy-based manipulators, such as regulation of B cell lymphoma 2 family proteins and caspase-dependent clearance of autophagy-related gene proteins, are likely to be the promising approaches for GIOP clinical treatments. In view of the important role of autophagy in the pathogenesis of GIOP, here we review the potential mechanisms about the impacts of autophagy in GIOP and its association with GIOP therapy.

Surgical Resection of Primary Ewing's Sarcoma of Bone Improves Overall Survival in Patients Presenting with Metastasis.

BACKGROUND Metastatic Ewing's sarcoma (ES) of bone has a poor prognosis. Because there have been few previous studies on the prognostic factors and clinical outcome in patients with ES who have metastases at presentation, the aim of this study was to use the Surveillance, Epidemiology, and End Results (SEER) database to compare the clinical outcome following single and combined radiation treatment and surgery. MATERIAL AND METHODS The SEER database was used to identify patients with ES who presented with bone involvement and metastasis between 1973 to 2015. Prognostic analysis was performed using the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS There were 643 patients identified from the SEER database. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 33.1% and 34.3%, respectively and the median OS and CSS were 29.0±1.9 and 29.0±2.1 months, respectively. Multivariate analysis identified age <20 years and surgical resection of the primary tumor to be significantly associated with improved OS. Radiation therapy was not an independent predictor of OS or CSS. Radiation therapy alone resulted in a significantly reduced the OS and CSS compared with surgical resection alone. Combined surgery and radiation therapy of the primary tumor did not significantly improve the OS or CSS of patients with ES and metastatic disease when compared with surgery alone. CONCLUSIONS Age <20 years and surgical resection of the primary tumor were significantly associated with improved OS in patients with primary ES of bone who presented with metastasis.

Mammalian target of rapamycin as a therapeutic target in osteoporosis.

The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy.

Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis.

MicroRNAs (miRNAs) are novel regulatory factors that play important roles in numerous cellular processes through the posttranscriptional regulation of gene expression. Recently, deregulation of the miRNA-mediated mechanism has emerged as an important pathological factor in osteoporosis. However, a detailed molecular mechanism between miRNAs and osteoporosis is still not available. In this review, the roles of miRNAs in the regulation of cells related to bone homeostasis as well as miRNAs that deregulate in human or animal are discussed. Moreover, the miRNAs that act as clusters in the biology of cells in the bone microenvironment and the difference of some important miRNAs for bone homeostasis between bone and other organs are mentioned. Overall, miRNAs that contribute to the pathogenesis of osteoporosis and their therapeutic potential are considered.

Plastrum Testudinis Extracts Promote BMSC Proliferation and Osteogenic Differentiation by Regulating Let-7f-5p and the TNFR2/PI3K/AKT Signaling Pathway.

BACKGROUND/AIMS: Plastrum testudinis extracts (PTE) show osteoprotective effects on glucocorticoid-induced osteoporosis in vivo and in vitro. However, the underlying molecular mechanism of PTE in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. METHODS: BMSC proliferation was investigated using the Cell Counting Kit-8 assay. BMSC differentiation and osteogenic mineralization were assayed using alkaline phosphatase and Alizarin red staining, respectively. The mRNA expression levels of Let-7f-5p, Tnfr2, Traf2, Pi3k, Akt, ß-catenin, Gsk3ß, Runx2, and Ocn were measured using real time quantitative polymerase chain reaction. Protein levels of TNFR2, TRAF2, p-PI3K, p-AKT, p-ß-CATENIN, and p-GSK3ß were analyzed by western blotting. The functional relationship of Let-7f-5p and Tnfr2 was determined by luciferase reporter assays. RESULTS: The optimum concentration for PTE was 30 µg/ml. PTE significantly promoted BMSC osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, ß-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3ß mRNA expression. PTE inhibited TNFR2, TRAF2, and p-ß-CATENIN protein expression, and promoted p-PI3K, p-AKT, and p-GSK3ß protein expression. In addition, Tnfr2 was a functional target of Let-7f-5p in 293T cells. CONCLUSIONS: Our results suggested that PTE may promote BMSC proliferation and osteogenic differentiation via a mechanism associated with the regulation of Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway.

A toxicological, metabonomic and transcriptional analysis to investigate the property of mulberry 1-deoxynojirimycin against the growth of Samia cynthia ricini.

1-Deoxynojirimycin (DNJ) is a natural d-glucose analogue from mulberry with promising physiological activity in vivo. Up to the present, the antidiabetic effects of DNJ on lowering blood sugar and accelerating lipid metabolism in mammals were broadly reported, but the specific character of DNJ against insects was vastly ignored. In this study, a toxicological test of DNJ againgst eri-silkworm, Samia cynthia ricini was carried out to investigate the potential of DNJ in insect management. Further, a method of nuclear magnetic resonance (NMR) metabonomics and real-time qPCR (RT-qPCR) were performed to analyze the alteration in midgut of eri-silkworm caused by DNJ. The result of toxicology showed that 5% and 10% DNJ could significantly inhibit the development of third-instar larvae on day 1-5, and mass deaths happened in DNJ groups on day 3-5. The quantitative analysis of 1H NMR in fifth-instar larvae showed that trehalose level increased in midgut of 0, 6 and 12 h DNJ groups, while the concentrations of glucose, lactate, alanine, pyruvate, α-ketoglutarate and fumarate were reduced in varying degrees. Meanwhile, principal component analysis (PCA) indicated that there were significant differences in the metabolic profiles among 12 h DNJ groups and the control group. In addition, RT-qPCR results displayed that four genes coding α-glucosidase, trehalase (THL) and lactate dehydrogenase (LDH) were lowered in expression of 12 h DNJ groups. Simultaneously, THL activity was significantly lowerd in 12 h DNJ groups. These mutually corroborated results indicated that the backbone pathways of energy metabolism, including hydrolysis of trehalose and glycogens, glycolysis and tricarboxylic acid (TCA) cycle were significantly inhibited by DNJ. Thus, the specific mechanism of DNJ efficiently suppressing the growth and energy metabolism of eri-silkworm was explored in this study, providing the potential of DNJ as to the production of botanical insecticide.