Secondary metabolites in host pears defense against two fruit borers and cytochrome-P450-mediated counter-defense.

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

INTRODUCTION: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. METHODS: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. RESULTS: Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. CONCLUSION: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Linkage of CDC42 and T-helper cell ratio with anxiety, depression and quality of life in ST-elevation myocardial infarction.

Objective: To investigate the correlations between CDC42 and T-cell subsets concerning anxiety, depression and quality of life in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention. Methods: Sera from 156 participants were analyzed for CDC42 levels and Th1, Th2, Th17 and Treg cells. Results: CDC42 correlated with reduced Th1/Th2 and Th17/Treg ratios, lower anxiety and depression, and higher EuroQol visual analog scale (EQ-VAS) score. The Th17/Treg ratio correlated with elevated anxiety, depression, EuroQol-5 dimensions score and decreased EQ-VAS score. The Th1/Th2 ratio was positively related to the EQ-VAS score. Conclusion: CDC42 correlates with reduced Th1/Th2 and Th17/Treg ratios, reduced anxiety and depression, and improved quality of life in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention.

CDC42 is a protein that regulates immune cells and negative mood. This study enrolled 156 patients with ST-elevation myocardial infarction (a severe type of coronary artery disease) who had percutaneous coronary intervention (a treatment that improves coronary blood flow). Their blood was collected for detecting CDC42 and specific immune cells, including Th1, Th2, Th17 and Treg cells. Their feelings of anxiety, depression and quality of life (QoL) were assessed using relevant questionnaires. The results showed that if a patient presented with reduced CDC42, they would have a high probability of anxiety and depression and poor QoL, as well as increased Th1 and Th17 cells. The study also found that patients with increased Th17 cells or decreased Treg cells would have a high possibility of anxiety and depression, as well as bad QoL. In addition, if a patient had increased Th2 cells, they would have a high probability of poor QoL. In summary, the detection of CDC42 can help ST-elevation myocardial infarction patients who have percutaneous coronary intervention better observe anxiety and depression.

Quercetin stimulates an accelerated burst of oviposition-based reproductive strategy in codling moth controlled by juvenile hormone signaling pathway.

The advantageous characteristics of invasive pests, particularly their ability to reproduce and adapt to the environment, have been observed. However, it remains unclear what specific inherent superiority enables fruit pests to successfully invade and dominate in interactions with other species. In this study, we report that Cydia pomonella (Linnaeus), a notorious invasive pest of pome fruits and walnuts globally, employs unique reproductive strategies in response to quercetin, a plant compound in host fruits. By monitoring adult dynamics and fruit infestation rates, we observed a competitive relationship between C. pomonella and the native species Grapholita molesta (Busck). C. pomonella was able to occupy vacant niches to ensure its population growth. We also found that quercetin had different effects on the reproductive capacity and population growth of C. pomonella and G. molesta. While quercetin stimulated the fecundity and population growth of G. molesta, it inhibited C. pomonella. However, C. pomonella was able to rapidly increase its population after exposure to quercetin by adopting an 'accelerated burst' of oviposition strategy, with each individual making a greater reproductive contribution compared to the control. We further demonstrated that the effect of quercetin on oviposition is regulated by the juvenile hormone (JH) signaling pathway in C. pomonella, allowing it to prioritize survival. The enhanced reproductive fitness of G. molesta in response to quercetin is attributed to the regulation of JH titers and key genes such as Met and Kr-h1, which in turn up-regulate reproduction-related genes Vg and VgR. In contrast, C. pomonella is inhibited. These findings shed light on the mechanisms interspecific competition and help to improve our understanding of the global spread of C. pomonella, which can be attributed to its inherent superiority in terms of reproductive strategy.

Associations between triglyceride glucose index and depression in middle-aged and elderly adults: A cross-sectional study.

The pathogenesis of depression is unclear, and it responds poorly to treatment. It is thus urgent to identify the pathogenesis of depression and possible therapeutic targets. There may be interactions between insulin resistance (IR) and depression. The purpose of this study was to explore the relationship between depression, triglyceride glucose (TyG) index. The study participants were 198 middle-aged and elderly patients who were admitted to the Hebei General Hospital between January 1, 2021, and August 31, 2022, together with 189 healthy adults as controls. Depression was diagnosed according to ICD-10 diagnostic criteria for depression. IR was assessed by the TyG index. Compared with the control group, patients suffering from depression had higher TyG index (P = .00); There were significant differences in the sex ratio (P = .00), family history (P = .00), body mass index (P = .008), total cholesterol (P = .00), fasting blood glucose (P = .004), high-density lipoprotein (P = .00), and low-density lipoprotein (P = .001) levels between the 2 groups. After excluding other confounding factors, the TyG index was found to be independently associated with depression, with an OR of 2.75. These data support an association of depression with the TyG index. IR thus appears to be a risk factor for depression.

Genome-wide identification, characterization, and expression profiling of ATP-binding cassette (ABC) transporter genes potentially associated with abamectin detoxification in Cydia pomonella.

The codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) is one of the most notorious pests of pome fruits and walnuts worldwide, which has developed resistance to almost all classes of insecticides, including abamectin (ABM). ATP-binding cassette (ABC) transporters are thought to play a vital roles in insecticide detoxification by reducing the toxic concentrations of insecticides in an organism tissues. Despite the tremendous progress in understanding the detoxification mechanisms at the molecular level, the physiological functions of ABC transporters in insects have been poorly investigated. In this study, we found that the ABC inhibitor verapamil synergized significantly the toxicity of ABM, suggesting a potential role of ABC in detoxification. A total of 54 ABC genes were identified in the third-instar larvae of C. pomonella after treatment with sublethal doses (LD10 and LD30) of ABM. The expression profile of these genes in ABM-treated larvae at different time points (24, 48, 72 hr) using transcriptomic analysis (RNA-seq) was also investigated. The results showed that the expression of about 30 ABC genes was significantly co-upregulated after treatment. Several specific genes were up-regulated at 48 hr after treatment of larvae with LD10 ABM. Among these up-regulated genes, we found that the relative expression level of the CPOM19553 was 29.7-fold and 16.0-fold higher when larvae were exposed to ABM at the LD10 and LD30 doses compared to control, respectively. Unlike other ABC genes, only CPOM08323 exhibited significant expression levels in the head and cuticle of the third-instar larvae of C. pomonella exposed to the two sublethal doses of ABM, with no expression was observed in the detoxification tissues such as midgut and Malpighian tubule. This study suggests that these up-regulated genes may be involved in ABM resistance in C. pomonella. Our findings will provide an additional information required for further analysis of ABC transporter genes associated with xenobiotic metabolism in C. pomonella.

Oxidative stress and autophagic alteration in brainstem of SOD1-G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease involving both upper and lower motor neurons. The mechanism of motor neuron degeneration is still unknown. Although many studies have been performed on spinal motor neurons, few have been reported on brainstem and its motor nuclei. The aim of this study was to investigate oxidative stress and autophagic changes in the brainstem and representative motor nuclei of superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. The expression levels of cluster of differentiation molecule 11b (CD11b), glial fibrillary acidic protein, glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, voltage-dependent anion-selective channel protein 1, Sequestosome 1/p62 (p62), microtubule-associated protein 1 light chain 3B (LC3), and SOD1 proteins in brainstem were examined by Western blot analysis. Immunohistochemistry and immunofluorescence were performed to identify the cellular localization of SOD1, p62, and LC3B, respectively. The results showed that there were progressive asctrocytic proliferation and microglial activation, induction of antioxidant proteins, and increased p62 and LC3II expression in brainstem of SOD1-G93A mice. Additionally, SOD1 and p62 accumulated in hypoglossal, facial, and red nuclei, but not in oculomotor nucleus. Furthermore, electron microscope showed increased autophagic vacuoles in affected brainstem motor nuclei. Our results indicate that brainstem share similar gliosis, oxidative stress, and autophagic changes as the spinal cord in SOD1-G93A mice. Thus, SOD1 accumulation in astrocytes and neurons, oxidative stress, and altered autophagy are involved in motor neuron degeneration in the brainstem, similar to the motor neurons in spinal cord. Therefore, therapeutic trials in the SOD1G93A mice need to target the brainstem in addition to the spinal cord.