Comparative connectomics of the descending and ascending neurons of the Drosophila nervous system: stereotypy and sexual dimorphism.

In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour, and the brain. In insects, the neck connective is both a physical and information bottleneck connecting the brain and the ventral nerve cord (VNC, spinal cord analogue) and comprises diverse populations of descending (DN), ascending (AN) and sensory ascending neurons, which are crucial for sensorimotor signalling and control. Integrating three separate EM datasets, we now provide a complete connectomic description of the ascending and descending neurons of the female nervous system of Drosophila and compare them with neurons of the male nerve cord. Proofread neuronal reconstructions have been matched across hemispheres, datasets and sexes. Crucially, we have also matched 51% of DN cell types to light level data defining specific driver lines as well as classifying all ascending populations. We use these results to reveal the general architecture, tracts, neuropil innervation and connectivity of neck connective neurons. We observe connected chains of descending and ascending neurons spanning the neck, which may subserve motor sequences. We provide a complete description of sexually dimorphic DN and AN populations, with detailed analysis of circuits implicated in sex-related behaviours, including female ovipositor extrusion (DNp13), male courtship (DNa12/aSP22) and song production (AN hemilineage 08B). Our work represents the first EM-level circuit analyses spanning the entire central nervous system of an adult animal.

Longitudinal associations between inhibitory control, gratitude, and positive parenting during early childhood.

Children's inhibitory control, which refers to the capability to recognize social and task demands by suppressing inappropriate behavior, is a key element closely related to both external and internal issues in preschoolers. The protective roles of parenting factors and social and moral functions, such as gratitude, remain unknown in the mechanism of inhibitory control. The present study employed a general cross-lagged panel model to explore the relationships between positive parenting, child gratitude, and inhibitory control. The research design involved repeated measurements based on parents' reports on 373 Chinese preschoolers in Hong Kong (179 males, 182 females; Mage = 4.51, SD = 0.60). The cross-lagged panel model revealed that positive parenting at Time 1 (T1) was significantly associated with preschool children's gratitude but not with inhibitory control at Time 2 (T2). Conversely, child gratitude at T1 was positively associated with inhibitory control at T2. These findings underscore the impact of positive parenting on gratitude and the predictive role of gratitude on inhibitory control. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Presence of meaning in life and meaning confusion mediate the effects of adverse childhood experiences on mental health among university students.

Few studies have explored meaning in life as a mediator between adverse childhood experiences (ACEs) and mental health. This study examined the protective and risk factors associated with meaning in life, as they mediate the effect of ACEs on mental health. The sample was 293 university students in Hong Kong (mean age = 21 years). The results of analyses based on three-wave longitudinal data and structural equation modeling demonstrated that the presence of meaning mediated the negative association between ACEs and happiness, and that meaning confusion mediated the positive association between ACEs and depression and anxiety. This study provides evidence that the presence of meaning may play a protective role and that meaning confusion may be a risk factor for the effects of ACEs on mental health. This study's results have implications for the development of prevention and intervention strategies to alleviate the detrimental impact of ACEs and promote mental health in young adults.

Whole-brain annotation and multi-connectome cell typing quantifies circuit stereotypy in Drosophila.

The fruit fly Drosophila melanogaster combines surprisingly sophisticated behaviour with a highly tractable nervous system. A large part of the fly's success as a model organism in modern neuroscience stems from the concentration of collaboratively generated molecular genetic and digital resources. As presented in our FlyWire companion paper 1 , this now includes the first full brain connectome of an adult animal. Here we report the systematic and hierarchical annotation of this ~130,000-neuron connectome including neuronal classes, cell types and developmental units (hemilineages). This enables any researcher to navigate this huge dataset and find systems and neurons of interest, linked to the literature through the Virtual Fly Brain database 2 . Crucially, this resource includes 4,552 cell types. 3,094 are rigorous consensus validations of cell types previously proposed in the hemibrain connectome 3 . In addition, we propose 1,458 new cell types, arising mostly from the fact that the FlyWire connectome spans the whole brain, whereas the hemibrain derives from a subvolume. Comparison of FlyWire and the hemibrain showed that cell type counts and strong connections were largely stable, but connection weights were surprisingly variable within and across animals. Further analysis defined simple heuristics for connectome interpretation: connections stronger than 10 unitary synapses or providing >1% of the input to a target cell are highly conserved. Some cell types showed increased variability across connectomes: the most common cell type in the mushroom body, required for learning and memory, is almost twice as numerous in FlyWire as the hemibrain. We find evidence for functional homeostasis through adjustments of the absolute amount of excitatory input while maintaining the excitation-inhibition ratio. Finally, and surprisingly, about one third of the cell types proposed in the hemibrain connectome could not yet be reliably identified in the FlyWire connectome. We therefore suggest that cell types should be defined to be robust to inter-individual variation, namely as groups of cells that are quantitatively more similar to cells in a different brain than to any other cell in the same brain. Joint analysis of the FlyWire and hemibrain connectomes demonstrates the viability and utility of this new definition. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open source toolchain for brain-scale comparative connectomics.

Colon-specific delivery of methotrexate using hyaluronic acid modified pH-responsive nanocarrier for the therapy of colitis in mice.

Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of clinical application of MTX, poly (lactic-co-glycolic acid) (PLGA), Eudragits® S100 (ES100), chitosan (CS) and hyaluronic acid (HA) were used to structure the MTX-loaded HA-CS/ES100/PLGA nanoparticles (MTX@hCEP). MTX@hCEP had a hydrodynamic particle size of approximately 202.5 nm, narrow size distribution, negative zeta potential (-18.7 mV), and smooth surface morphology. In vitro drug release experiments under simulated gastrointestinal conditions indicated that MTX@hCEP exhibited colonic pH-sensitive drug release properties. The cellular uptake capacity of hCEP nanoparticles was significantly enhanced in RAW 264.7 macrophages. Moreover, we further found that the MTX@hCEP also inhibited the proliferation and the secretion of pro-inflammatory cytokines in the LPS-stimulated macrophages. In vivo imaging results not only demonstrated that the accumulated in the colon of colitis mice, but also indicated the extended retention time of MTX in the colon. Additionally, MTX@hCEP alleviated inflammatory symptoms via decreasing the activities of myeloperoxidase and pro-inflammatory factors, promoting mucosal repair in vivo. Collectively, these results clearly demonstrated that MTX@hCEP with properties of colon-specific and macrophages targeting can be exploited as an efficient nanotherapeutic for IBD therapy.

XA pH-Responsive and Colitis-Targeted Nanoparticle Loaded with Shikonin for the Oral Treatment of Inflammatory Bowel Disease in Mice.

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and anti-inflammatory cytokines (IL-10 and TGF-ß), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.

Network analysis on the relationship between posttraumatic stress disorder, psychiatric co-morbidity and posttraumatic growth among Chinese adolescents.

BACKGROUND: This study investigated the association between posttraumatic stress disorder (PTSD), psychiatric co-morbidity and posttraumatic growth (PTG) among Chinese adolescents using network analysis. METHODS: 867 Chinese adolescents (male = 424, female = 443) were recruited from three secondary schools. They completed the Posttraumatic Stress Disorder Checklist for DSM-5, the Posttraumatic Growth Inventory, and the General Health Questionnaire-28. RESULTS: Domains of each construct mainly clustered within their respective communities with several bridging edges identified. The prominent roles of bridging nodes and edges (positive and negative) were highlighted. Key bridging nodes were negative alterations in cognitions and mood for PTSD, anxiety and insomnia for psychiatric co-morbidity and appreciation of life for PTG. LIMITATIONS: The cross-sectional nature of the present study may preclude the identification of real causal relationships between nodes. CONCLUSIONS: Following a trauma, adolescents displayed posttraumatic stress along with general psychological disorder symptoms. These distress reactions could affect the way they appreciated life and their motivation to seek future life possibilities. Findings from the current study may provide some clue for the facilitation of posttraumatic growth among clinical patients.

Intratumoral analysis of digital breast tomosynthesis for predicting the Ki-67 level in breast cancer: A multi-center radiomics study.

PURPOSE: To non-invasively evaluate the Ki-67 level in digital breast tomosynthesis (DBT) images of breast cancer (BC) patients based on subregional radiomics. METHODS: A total of 266 patients who underwent DBT scans were consecutively enrolled at two centers, between September 2017 and September 2021. The whole tumor region was partitioned into various intratumoral subregions, based on individual- and population-level clustering. Handcrafted radiomics and deep learning-based features were extracted from the subregions and from the whole tumor region, and were selected by least absolute shrinkage and selection operator (LASSO) regression, yielding radiomics signatures (RSs). The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the developed RSs. RESULTS: Each breast tumor region was partitioned into an inner subregion (S1) and a marginal subregion (S2). The RSs derived from S1 always generated higher AUCs compared with those from S2 or from the whole tumor region (W), for the external validation cohort (AUCs, S1 vs. W, handcrafted RSs: 0.583 [95% CI, 0.429-0.727] vs. 0.559 [95% CI, 0.405-0.705], p-value: 0.920; deep RSs: 0.670 [95% CI, 0.516-0.802] vs. 0.551 [95% CI, 0.397-0.698], p-value: 0.776). The fusion RSs, combining handcrafted and deep learning-based features derived from S1, yielded the highest AUCs of 0.820 (95% CI, 0.714-0.900) and 0.792 (95% CI, 0.647-0.897) for the internal and external validation cohorts, respectively. CONCLUSIONS: The subregional radiomics approach can accurately predict the Ki-67 level based on DBT data; thus, it may be used as a potential non-invasive tool for preoperative treatment planning in BC.

A longitudinal study of the impact of parental discipline on wellbeing among primary school students in China: The roles of school attachment and growth mindset.

BACKGROUND: Various parental disciplinary strategies may have different impacts on children's wellbeing. Protective factors, such as school attachment and a growth mindset, may mitigate the influence of harsh discipline on a child's wellbeing. OBJECTIVE: Based on the strengths-based trauma-informed positive education model, the current study investigated the impacts of three types of parental discipline (corporal punishment, psychological aggression, and nonviolent discipline) on primary school students' wellbeing and examined the moderating roles of school attachment and a growth mindset (both disjunctive and conjunctive moderating effects) in the relationship between parental discipline and student wellbeing. METHODS: A sample of 854 primary school students (M = 9.40) from eight schools in Hong Kong, China, completed the questionnaire survey at two time points (Time 1 and Time 2), one year apart. Hierarchical regression analysis was applied for data analysis. RESULTS: Parental psychological aggression at Time 1 (T1) was significantly and negatively related to student wellbeing at Time 2 (T2). Parental nonviolent discipline students' school attachment and growth mindset at T1 were significantly and positively correlated with student wellbeing at T2, when controlling for the students' initial wellbeing and important confounding demographic variables. School attachment moderated the association between parental psychological aggression and student wellbeing. CONCLUSIONS: Parental psychological aggression has negative impacts while nonviolent discipline has positive impacts on primary school students' wellbeing. Students who are more attached to school and have a growth mindset show higher levels of wellbeing. The study provides further evidence of the role of school attachment in moderating the effect of parental psychological aggression on children's wellbeing in the trauma-informed positive education model.

CsAtf1, a bZIP transcription factor, is involved in fludioxonil sensitivity and virulence in the rubber tree anthracnose fungus Colletotrichum siamense.

In phytopathogenic fungi, the HOG MAPK pathway has roles in osmoregulation, fungicide sensitivity, and other processes. The ATF1/CREB-activating transcription factor Atf1 is a regulator that functions downstream of the HOG MAPK pathway. Here, we identified a gene, designated CsAtf1, that encodes a bZIP transcription factor in Colletotrichum siamense, which is the main pathogen that causes Colletotrichum leaf fall disease in rubber trees in China. CsAtf1 localizes to the nucleus. Its mRNA expression correlates positively with that of CsPbs2 and CsHog1 in the HOG MAPK pathway in response to activator (anisomycin), inhibitor (SB203580) and fludioxonil treatments. The CsAtf1 deletion mutant showed slightly retarded mycelial growth, small conidia, slow spore germination, and abnormal appressorium formation. This mutant showed the increased spore germination rate after fludioxonil treatment and more resistance to the fungicide fludioxonil than did the wild-type fungus. However, unlike deletion of Pbs2 or Hog1, which resulted in greater sensitivity to osmotic stress, the CsAtf1 deletion induced slightly increased resistance to osmotic stress and the cell wall stress response. The ΔCsAtf1 strain also exhibited significantly reduced virulence on rubber tree leaves. These data revealed that CsAtf1 plays a key role in the regulation of fludioxonil sensitivity and in pathogenicity regulation in C. siamense.

Post-Traumatic Distress and Burnout Among Chinese School Teachers: The Mediating Role of Forgiveness.

PURPOSE: Teachers' mental health is concerning due to high stress at work. Its association with job-related stressors has been well-documented. Little is known; however, about how traumatic life events and trauma reactions might contribute to their psychological distress. This paper is to explore whether Post-traumatic Stress Disorder (PTSD) following past traumatic event would predict burnout and psychiatric co-morbidity among Chinese k-12 school teachers and whether this prediction would be mediated by forgiveness after controlling for work-related factors. METHODS: Two hundred and seventy-nine Chinese teachers (F = 223, M = 56) from primary and secondary schools completed demographic information, Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Heartland Forgiveness Scale (HFS), General Health Questionnaire-28 (GHQ-28), Maslach Burnout Inventory-Educator's Survey (MBI-ES), and a series of measures assessing work-related factors. RESULTS: Structured equation modeling (SEM) showed that after controlling for work-related factors, PTSD following past trauma was positively associated with burnout and general psychological problems but negatively associated with levels of forgiveness. Forgiveness carried the impact of PTSD onto burnout rather than general psychological distress. CONCLUSION: To conclude, regardless of the level of stress experienced from working in school, primary and secondary teachers with PTSD from past trauma found it more difficult forgiving which in turn could affect their levels of burnout.

A Bayesian semi-parametric model for thermal proteome profiling.

The thermal stability of proteins can be altered when they interact with small molecules, other biomolecules or are subject to post-translation modifications. Thus monitoring the thermal stability of proteins under various cellular perturbations can provide insights into protein function, as well as potentially determine drug targets and off-targets. Thermal proteome profiling is a highly multiplexed mass-spectrommetry method for monitoring the melting behaviour of thousands of proteins in a single experiment. In essence, thermal proteome profiling assumes that proteins denature upon heating and hence become insoluble. Thus, by tracking the relative solubility of proteins at sequentially increasing temperatures, one can report on the thermal stability of a protein. Standard thermodynamics predicts a sigmoidal relationship between temperature and relative solubility and this is the basis of current robust statistical procedures. However, current methods do not model deviations from this behaviour and they do not quantify uncertainty in the melting profiles. To overcome these challenges, we propose the application of Bayesian functional data analysis tools which allow complex temperature-solubility behaviours. Our methods have improved sensitivity over the state-of-the art, identify new drug-protein associations and have less restrictive assumptions than current approaches. Our methods allows for comprehensive analysis of proteins that deviate from the predicted sigmoid behaviour and we uncover potentially biphasic phenomena with a series of published datasets.

The Impact of Past Trauma on Psychological Distress: The Roles of Defense Mechanisms and Alexithymia.

OBJECTIVES: Posttraumatic stress disorder (PTSD) symptoms following past trauma could lead to psychological distress. Little is known, however, about the roles of defense mechanisms and alexithymia may play in the process. The current study aimed to examine the potential impact of alexithymia and defense mechanisms on the relationship between past trauma and distress among Chinese university students. METHOD: 455 university students completed a set of questionnaires: PTSD Checklists for DSM-5, Toronto Alexithymia Scale (TAS-20), Defense Style Questionnaire, and General Health Questionnaire-28. RESULTS: PTSD following past trauma was associated with increased psychological distress. Alexithymia and defenses (especially immature defense) mediated the path between PTSD and psychological co-morbidities. CONCLUSION: Following past trauma, people developed PTSD and other psychological symptoms. The severity of these distress symptoms was influenced by the way they defended themselves psychologically, and their ability to identify, express, and process distressing emotions.

Detection of patient-ventilator asynchrony from mechanical ventilation waveforms using a two-layer long short-term memory neural network.

BACKGROUND AND OBJECTIVE: Mismatch between invasive mechanical ventilation and the requirements of patients results in patient-ventilator asynchrony (PVA), which is associated with a series of adverse clinical outcomes. Although the efficiency of the available approaches for automatically detecting various types of PVA from the ventilator waveforms is unsatisfactory, the feasibility of powerful deep learning approaches in addressing this problem has not been investigated. METHODS: We propose a 2-layer long short-term memory (LSTM) network to detect two most frequently encountered types of PVA, namely, double triggering (DT) and ineffective inspiratory effort during expiration (IEE), on two datasets. The performance of the networks is evaluated first using cross-validation on the combined dataset, and then using a cross testing scheme, in which the LSTM networks are established on one dataset and tested on the other. RESULTS: Compared with the reported rule-based algorithms and the machine learning models, the proposed 2-layer LSTM network exhibits the best overall performance, with the F1 scores of 0.983 and 0.979 for DT and IEE detection, respectively, on the combined dataset. Furthermore, it outperforms the other approaches in cross testing. CONCLUSIONS: The findings suggest that LSTM is an excellent technique for accurate recognition of PVA in clinics. Such a technique can help detect and correct PVA for a better patient ventilator interaction.

Adolescents' Mindfulness and Psychological Distress: The Mediating Role of Emotion Regulation.

Mindfulness has been widely linked with psychological well-being in general population. There are emerging studies supporting the relationship between adolescents' mindfulness and their mental health. However, the mechanisms through which mindfulness may influence adolescents' psychological distress have only recently been explored, and more related research is still needed. This study investigated the relationship between adolescents' dispositional mindfulness and psychological symptoms of depression, anxiety and stress. The mediating variables were also explored in perspective of two common emotion regulation theories, which were measured through Difficulties in Emotion Regulation Scale (DERS) and Emotion Regulation Questionnaire (ERQ). DERS has been used as a comprehensive assessment of emotion regulation difficulties. ERQ is also widely accepted to measure the emotion regulation process including dimensions of cognitive reappraisal and expressive suppression. Measures assessing mindfulness, emotion regulation, and psychological distress were administered to 1067 adolescents in mainland China. The results confirmed that adolescents' dispositional mindfulness was negatively associated with depression, anxiety, and stress. DERS, especially the sub-dimensions of Acceptance and Strategies, significantly mediated the relationship between mindfulness and symptoms of depression, anxiety and stress. Whereas, ERQ including subscales of cognitive reappraisal and expressive suppression exerted limited mediating effect. These findings provided insights for the potential underlying mechanism between adolescents' mindfulness and psychological distress, demonstrating that DERS might be more pervasive than ERQ. Further research was suggested to explore other mediating variables underlying mindfulness and psychological distress among adolescents and develop mindfulness-based programs to improve adolescents' mindfulness and emotion regulation ability.

New Insights into Sediment Transport in Interconnected River-Lake Systems Through Tracing Microorganisms.

A growing awareness of the wider environmental significance of diffuse sediment pollution in interconnected river-lake systems has generated the need for reliable provenance information. Owing to their insufficient ability to distinguish between multiple sources, common sediment source apportionment methods would rarely be a practical solution. On the basis of the inseparable relationships between sediment and adsorbed microorganisms, community-based microbial source tracking may be a novel method of identifying dominant sediment sources in the era of high-throughput sequencing. Dongting Lake was selected as a study area as it receives considerable sediment import from its inflowing rivers during the flood season. This study was conducted to characterize the bacterial community composition of sediment samples from the inflow-river estuaries and quantify their sediment microbe contributions to the central lake. Metagenomic analysis revealed that the community compositions of source sediment samples were significantly different, allowing specific sources to be identified with the machine learning classification program SourceTracker. A modified analysis using SourceTracker found that the major contributors to three major lake districts were the Songzi, Zishui, and Xinqiang Rivers. The impacts of hydrodynamic conditions on source apportionment were further verified and suggested the practicability of this method to offer a systematic and comprehensive understanding of sediment sources, pathways, and transport dynamics. Finally, a novel framework for sediment source-tracking was established to develop effective sediment management and control strategies in river-lake systems.

The impact of past trauma on psychological distress among Chinese students: The roles of cognitive distortion and alexithymia.

Past traumatic events are distressing experiences which can result in the emergence of posttraumatic stress disorders (PTSD) and other psychological symptoms among university students. However, little is known as to whether or not cognitive distortion and alexithymia would influence the severity of these distress outcomes. This study examined a cognitive-emotional framework depicting potential roles that cognitive distortion and alexithymia could play in influencing the relationship between past trauma and psychiatric co-morbidities among university students in China. One thousand one hundred and eleven participants completed the PTSD Checklist for DSM-5, Cognitive Distortion Scale (CDS), Toronto Alexithymia Scale (TAS-20), and General Health Questionnaire (GHQ-28). Results indicated that PTSD following past trauma was significantly associated with increased psychiatric co-morbidities after controlling for covariates. Both alexithymia and distorted cognition mediated the association between PTSD and psychiatric co-morbidities. To conclude, university students can develop PTSD from past trauma and other mental health problems. The severity of psychological distress can be influenced by their distorted perceptions of themselves, the world, and the future, as well as their ability to identify, describe, and express distressing emotions.

The impact of posttraumatic stress symptoms, posttraumatic stress cognitions and interpersonal dependency on psychological co-morbidities following relationship dissolution among college students.

BACKGROUND: Relationship dissolution is a distressing experience which can result in the emergence of posttraumatic stress (i.e. post-dissolution PTSS) and other psychological symptoms among college students. Little is known, however, whether posttraumatic stress cognitions and interpersonal dependency may influence the severity of these distress outcomes. AIMS: This study examined the interrelationship between posttraumatic stress symptoms (PTSS), posttraumatic stress cognitions, interpersonal dependency and psychological co-morbidities following relationship dissolution. METHODS: One hundred and eighty college students (M = 69, F = 111) who had experienced relationship dissolution completed the Posttraumatic Stress Diagnostic Scale, Posttraumatic Stress Cognition Inventory, Interpersonal Dependency Inventory and General Health Questionnaire-28. RESULTS: Posttraumatic stress symptoms following relationship dissolution (post-dissolution PTSS) were associated with increased psychological co-morbidities. Negative view of oneself and self-blame mediated between PTSS and psychological co-morbidities. Assertion of autonomy moderated the mediational effects of negative cognitions on psychological co-morbidities. CONCLUSIONS: People can develop PTSSs and other psychological symptoms following the dissolution of a romantic relationship. Their concept of self and tendency to seek independence and control played a key role in determining the severity of distress symptoms.

No cross-resistance between imidacloprid and pymetrozine in the brown planthopper: status and mechanisms.

Cross-resistance between insecticides, especially from different groups, can be extremely unpredictable, and it has been a serious concern in pest control. Pymetrozine has been widely used to control Nilaparvata lugens with the suspension of imidacloprid for the resistance, and N. lugens has showed obvious pymetrozine resistance in recent years. To investigate the possible cross-resistance between imidacloprid and pymetrozine is very important to avoid the adverse effects on resistance development and pest control. Bioassays of two field populations in five consecutive years showed that imidacloprid resistance decreased greatly, while pymetrozine resistance increased significantly. The synergist piperonyl butoxide (PBO) could synergize both imidacloprid and pymetrozine in all field populations, which indicated the importance of P450s in the resistance to two insecticides. Imidacloprid resistance was reported to be associated with two P450s, CYP6AY1 and CYP6ER1, which could metabolize imidacloprid efficiently. However, the recombinant proteins of these two P450s did not show any enzymatic activity to metabolize pymetrozine. The pymetrozine susceptibility did not change when CYP6AY1 and CYP6ER1 mRNA levels were reduced by RNA interference (RNAi), although which could obviously decrease imidacloprid resistance. In vivo and in vitro studies provided evidences to demonstrate that there was no cross-resistance between imidacloprid and pymetrozine in N. lugens, which was different from the findings in Bemisia tabaci.

Toxicokinetics of naringin, a putative antitussive, after 184-day repeated oral administration in rats.

The toxicokinetic characteristics of naringin were investigated in rats that had been orally administered naringin extract, a candidate for oral treatment of cough, prepared from Citrus grandis "Tomentosa", at 50, 250, or 1250 mg/kg/day in a repeated-dose study for 1, 32, 93, or 184 days. Increased values of the mean systemic exposure were approximately proportional to increases in dose levels during all collection intervals; no saturation was observed. No significant differences in mean systemic exposure were observed between male and female rats. Results provide a reference for interpretation of toxicology findings and relevance to clinical safety issues.