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Silkworm ( Bombyx mori), a model Lepidoptera insect, is economically important. Its growth and development are regulated by endogenous hormones. During the process of transition from larvae to pupae, 20-hydroxyecdysone (20E) plays an important role. The recent surge in consumer products and applications using metallic nanoparticles has increased the possibility of human or ecosystem exposure due to their unintentional release into the environment. We investigated the effects of exposure to titanium dioxide nanoparticles (TiO NPs) on the action of 20E in B. mori. Titanium dioxide nanoparticle treatment shortened the molting duration by 8 hr and prolonged the molting peak period by 10 %. Solexa sequencing profiled the changes in gene expression in the brain of fifth-instar B. mori in response to TiONPS exposure for 72 hr, to address the effects on hormone metabolism and regulation. Thirty one genes were differentially expressed. The transcriptional levels of pi3 k and P70 S6 K, which are involved in the target of the rapamycin (TOR) signaling pathway, were up-regulated. Transcriptional levels of four cytochrome P450 genes, which are involved in 20E biosynthesis, at different developmental stages (48, 96, 144, and 192 hr) at 5th instars of all displayed trends of increasing expression. Simultaneously, the ecdysterone receptors, also displayed increasing trends. The 20E titers at four developmental stages during the 5th instar were 1.26, 1.23, 1.72, and 2.16 fold higher, respectively, than the control group. These results indicate that feeding B. mori with TiO NPs stimulates 20E biosynthesis, shortens the developmental progression, and reduces the duration of molting. Thus, application of TiO NPs is of high significance for saving the labor force in sericulture, and our research provides a reference for the ecological problems in the field of Lepidoptera exposured to titanium dioxide nanoparticles. [ABSTRACT FROM AUTHOR]

Highlights: [•] We performed a DGE analysis of the midgut in the B. mori at 24h exposed to phoxim. [•] The impact on detoxification, apoptosis and immune defense were addressed. [•] Phoxim exposure leads to increased apoptosis. [Copyright &y& Elsevier]

Florfenicol (FF) is a new antibiotic commonly used in sericulture. This study aimed to examine the effects of low (LC: 0.06 g/L), medium (MC: 0.12 g/L), and high (HC: 1.2 g/L) concentrations of FF on the midgut physiological functions of the silkworm, Bombyx mori (L.) (Lepidoptera: Bombycidae). The results showed that the body weight and the whole cocoon weight of silkworms decreased and the development duration of the fifth instar was prolonged in the HC group. The structure of intestinal microbiota of silkworm larvae was changed by high FF exposure. Specifically, the abundance of conditional pathogens (Curtobacterium, Sanguibater, etc.) was significantly increased, whereas the abundance of Pseudomonas and Pedobacter was decreased significantly. Additionally, the intestinal reactive oxygen species level at 72 h was significantly elevated, and the muscle layer had become loose, together with the appearance of gut goblet cell atrophy. We observed that the increase in Lactobacillus abundance led to a reduction in intestinal fluid pH, resulting in decreased α‐amylase and protease activities, whereas lipase activity exhibited an elevation. The results demonstrated that the accumulation of peroxides induced by exposure to 1.2 g/L FF caused intestinal damage, and the decrease in pH resulting from alterations in microbial composition and structure affected digestive enzyme activity, collectively leading to physiological impairment of the silkworm midgut. These findings provide a valuable reference for the safe use of FF in sericulture. [ABSTRACT FROM AUTHOR]

Silkworm (Bombyx mori) is an economically important insect. However, the survival of silkworms has been significantly affected by the assault of chemical pesticides on mulberry trees through aerial application and water currents. Phoxim is a broad-spectrum organophosphorus insecticide widely used in China. Currently, very little is known about the non-neuronal effects of sublethal exposure to phoxim. The purpose of this study was to investigate the non-neuronal effects of sublethal phoxim exposure in the silkworm midgut, with a focus on nutrient metabolism. After phoxim treatment, lipase activity in the silkworm was shown to be up-regulated at 24 h before a decreasing trend was seen. Meanwhile, α-amylase activity showed the opposite trend. The expression levels of mitochondrial respiratory chain-related genes were all up-regulated at 24 h before falling continuously. To ensure that the effects of phoxim on nutrient metabolism were not simply a consequence of a decrease in mulberry consumption, the silkworms were treated with a reduced-food diet before the digestive enzyme activities and the transcription levels of mitochondrial respiratory chain-related genes were analyzed. Our results showed that the patterns in the reduced-diet and phoxim-exposed silkworm were markedly different, suggesting the alterations in the phoxim-exposed silkworm cannot readily be explained by nutrient deprivation Unlabelled Image • Phoxim exposure alters the mRNA levels of glucose and lipid metabolism-related genes. • Lipase activity showed the opposite trend to α-amylase activity after exposure. • The patterns in the reduced-diet and phoxim-exposed silkworm were markedly different. [ABSTRACT FROM AUTHOR]

Although traumatic brain injury (TBI) is a common cause of death and disability worldwide, there is currently a lack of effective therapeutic drugs and targets. To reveal the complex pathophysiologic mechanisms of TBI, we performed transcriptome analysis of the mouse cerebral cortex and immunohistochemical analysis of human cerebral tissues. The genes Mt1, Mt2, Il33, and Fth1 were upregulated post-TBI and enriched in pathways associated with the inflammatory response, oxidative phosphorylation, and ferroptosis. As an agonist of MT1/2, melatonin (MLT) confers anti-oxidant, anti-inflammatory, and anti -ferroptosis effects after TBI. However, whether these upregulated genes and their corresponding pathways are involved in the neuroprotective effect of MLT remains unclear. In this study, interventions to inhibit MT1/2, IL-33, and ferroptosis (i.e., ferritin H (Fth)- KO) were applied post-TBI. The results showed that MLT attenuated TBI-induced cerebral edema and neurological outcomes by inhibiting inflammation and ferroptosis. Mechanistically, MLT mainly suppressed inflammatory responses and ferroptosis via the activation of MT2 and IL-33 pathways. Building on the previous finding that Fth deletion increases susceptibility to ferroptosis post-TBI, we demonstrated that Fth depletion remarkably exacerbated the post-TBI inflammatory response, and abolished the anti-inflammatory effects of MLT both in vivo and in vitro. Furthermore, the post-TBI anti-inflammatory effect of MLT, which occurs by promoting the polarization of CD206+ macrophages, was dependent on Fth. Taken together, these results clarified that MLT alleviates inflammation- and ferroptosis-mediated brain edema and neurological deficits by activating the MT2/IL-33/Fth pathway, which provides a novel target and theoretical basis for MLT to treat TBI patients. [Display omitted] • The up-regulated genes Mt1, Mt2, Il33, and Fth1 post-TBI were identified by transcriptome. • Melatonin, an agonist of MT1/2, inhibited inflammation and ferroptosis via MT2 and IL-33 pathways. • Fth depletion exacerbated inflammation and ferroptosis, except for IL-33 expression post-TBI. • Melatonin promoted the activation of CD206+ macrophage to exert anti-inflammation dependent on Fth. • Melatonin alleviated post-TBI edema and neurological outcomes by the MT2/IL-33/Fth signaling. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of regulated cell death that is mainly triggered by iron-dependent lipid peroxidation. A growing body of evidence suggests that ferroptosis is involved in the pathophysiology of traumatic brain injury (TBI), and tropomyosin-related kinase B (TrkB) deficiency would mediate TBI pathologies. As an agonist of TrkB and an immediate precursor of melatonin, N-acetyl serotonin (NAS) exerts several beneficial effects on TBI, but there is no information regarding the role of NAS in ferroptosis after TBI. Here, we examined the effect of NAS treatment on TBI-induced functional outcomes and ferroptosis. Remarkably, the administration of NAS alleviated TBI-induced neurobehavioral deficits, lesion volume, and neurodegeneration. NAS also rescued TBI-induced mitochondrial shrinkage, the changes in ferroptosis-related molecule expression, and iron accumulation in the ipsilateral cortex. Similar results were obtained with a well-established ferroptosis inhibitor, liproxstatin-1. Furthermore, NAS activated the TrkB/PI3K/Akt/Nrf2 pathway in the mouse model of TBI, while inhibition of PI3K and Nrf2 weakened the protection of NAS against ferroptosis both in vitro and in vivo , suggesting that a possible pathway linking NAS to the action of anti-ferroptosis was TrkB/PI3K/Akt/Nrf2. Given that ferritin H (Fth) is a known transcription target of Nrf2, we then investigated the effects of NAS on neuron-specific Fth knockout (Fth -KO) mice. Strikingly, Fth deletion almost abolished the protective effects of NAS against TBI-induced ferroptosis and synaptic damage, although Fth deletion-induced susceptibility toward ferroptosis after TBI was reversed by an iron chelator, deferoxamine. Taken together, these data indicate that the TrkB agonist NAS treatment appears to improve brain function after TBI by suppressing ferroptosis, at least in part, through activation of the PI3K/Akt/Nrf2/Fth pathway, providing evidence that NAS is likely to be a promising anti-ferroptosis agent for further treatment for TBI. [Display omitted] • NAS reduces TBI-induced neurological deficits and neurodegeneration. • NAS is a potent anti-ferroptotic compound, and mitigates TBI-induced ferroptosis. • NAS prevents TBI-induced ferroptosis through the PI3K/Akt/Nrf2/Fth pathway. • Fth deletion abolishes the effects of NAS on TBI-induced ferroptosis and synaptic damage. [ABSTRACT FROM AUTHOR]

Accumulating evidence demonstrates that ferroptosis may be important in the pathophysiological process of traumatic brain injury (TBI). As a major hormone of the pineal gland, melatonin exerts many beneficial effects on TBI, but there is no information regarding the effects of melatonin on ferroptosis after TBI. As expected, TBI resulted in the time‐course changes of ferroptosis‐related molecules expression and iron accumulation in the ipsilateral cortex. Importantly, we found that treating with melatonin potently rescued TBI induced the changes mentioned above and improved functional deficits versus vehicle. Similar results were obtained with a ferroptosis inhibitor, liproxstatin‐1. Moreover, the protective effect of melatonin is likely dependent on melatonin receptor 1B (MT2). Although ferritin plays a vital role in iron metabolism by storing excess cellular iron, its precise function in the brain, and whether it involves melatonin's neuroprotection remain unexplored. Considering ferritin H (Fth) is expressed predominantly in the neurons and global loss of Fth in mice induces early embryonic lethality, we then generated neuron‐specific Fth conditional knockout (Fth‐KO) mice, which are viable and fertile but have altered iron metabolism. In addition, Fth‐KO mice were more susceptible to ferroptosis after TBI, and the neuroprotection by melatonin was largely abolished in Fth‐KO mice. In vitro siFth experiments further confirmed the results mentioned above. Taken together, these data indicate that melatonin produces cerebroprotection, at least partly by inhibiting neuronal Fth‐mediated ferroptosis following TBI, supporting the notion that melatonin is an excellent ferroptosis inhibitor and its anti‐ferroptosis provides a potential therapeutic target for treating TBI. [ABSTRACT FROM AUTHOR]

Global warming is known to affect the growth, development and reproduction of insects. In this study, the larvae developmental process and endogenous hormone levels under high temperature (36 °C) stress were investigated in the lepidopteran model insect Bombyx mori (B. mori). After high temperature treatment, the duration of 5th instar larvae was shortened by 28 ± 2 h, the content of 20-hydroxyecdysone(20E) in hemolymph was significantly increased, and the transcription levels of the 20E response genes E93, Br–C, USP and E75 were up-regulated by 1.35-, 1.25-, 1.28-, and 1.27-fold, respectively. High temperature treatment also elevated the phosphorylation level of Akt and activated the downstream BmCncC/keap1 pathway, and the transcription levels of the 20E synthesis-related genes cyp302a1, cyp306a1, cyp314a1 and cyp315a1 were up-regulated by 1.12-, 1.51-, 2.17- and 1.23-fold, respectively. The transcription levels of cyp302a1 and cyp306a1 were significantly decreased in BmN cells after treatment with the double stranded RNA of BmCncC (dsBmCncC), whereas their transcription levels were significantly increased (2.15- and 1.31-fold, respectively) after treatment with the CncC agonist Curcumin. These results demonstrated that high temperature treatment promoted the metamorphosis and the BmCncC/keap1 pathway played a role in the metamorphosis of B. mori. Our results provided clues for understanding the CncC/keap1 pathway-mediated regulation of metamorphosis of Lepidopteran insects. • High temperature stress promotes the larvae development and changes endogenous hormone levels. • The activation of BmCncC/keap1 pathway is one of the reasons for the increase of 20E level. • BmCncC mediates ecdysone synthesis via Cyp302a1 and Cyp306a1. [ABSTRACT FROM AUTHOR]

Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission. Our previous studies proved that the inhibition of Drp1 may help attenuate traumatic brain injury (TBI)-induced functional outcome and cell death through maintaining normal mitochondrial morphology and inhibiting activation of apoptosis. However, the molecular mechanisms of Drp1 after TBI remain poorly understood. In this study, we investigated the role of mitochondrial division inhibitor 1 (Mdivi-1), a small molecule inhibitor of Drp1, in underlying mechanisms of general autophagy and mitochondria autophagy (mitophagy) after experimental TBI. In vivo , we found that autophagosomes accumulated in cortical neurons at 24 h after TBI, owing to the enhanced autophagy indicated by the accumulation of LC3 and the decrease of p62; but Mdivi-1 reversed the enhancement. Mdivi-1 also alleviated the number of LC3 puncta and TUNEL-positive structures in cells, indicating that autophagy maybe involved in Mdivi-1′s anti-apoptosis effects. Then, the expression level of mitochondrial dynamics related and mitophagy related proteins was assessed using the isolated mitochondria. The results showed that TBI-induced mitochondrial fission (represented by Drp1), mtDNA concentration down-regulation and PTEN induced putative kinase 1 (PINK1)-Parkin mediated mitophagy activation were all inhibited by Mdivi-1. In addition, TBI-induced blood-brain barrier (BBB) disruption and matrix metalloproteinases (MMP)-9 expression up-regulation were inhibited following Mdivi-1 treatment. In vitro , Mdivi-1 significantly alleviated the scratch injury-induced cell death, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production and ATP reduction in primary cortical neurons (PCNs). Additionally, the lysosome inhibitor chloroquine (CQ) abrogated the Mdivi-1-induced decrease in autophagosomes accumulation and cell death at 24 h both in the basal state and under the conditions of scratch cell injury. Together, these data demonstrate that Mdivi-1 mitigates TBI-induced BBB disruption and cell death at least in part by a mechanism involving inhibiting autophagy dysfunction and mitophagy activation. [ABSTRACT FROM AUTHOR]