Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double-blind, controlled trial.

BACKGROUND: To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory study aimed to assess the efficacy and safety of remimazolam at a single induced dose for deep sedation in elderly patients undergoing diagnostic flexible bronchoscopy (DFB), and compare with midazolam, a commonly used sedative. METHODS: A total of 100 elderly patients (age range 65-80 yr; American Society of Anesthesiologists Physical Status I-III) undergoing DFB were randomly allocated into 2 groups according to the sedatives used for induction: the remimazolam group and the midazolam group. Sedation induction was initiated by an intravenous bolus of remimazolam (0.135 mg/kg) or midazolam (0.045 mg/kg), respectively, both groups were combined with a high-dose of alfentanil (18 µg/kg), and supplemented with high-flow nasal cannula (HFNC) oxygen supply at a flow rate of 45 L/min. If the target depth of sedation was not achieved, propofol would be titrated as a rescue. The primary outcome was the success rate of sedation at a single induced dose to achieve target depth (Ramsay sedation score [RSS] = 4) during induction, intraoperative changes in vital signs, postoperative follow-up situation and incidence of post-bronchoscopy adverse events were evaluated as secondary outcomes. RESULTS: The success rate of sedation in the remimazolam group was significantly higher than that in the midazolam group (65.2% vs 39.6%, P = .013), while the incidence of extra sleep within 6 hours after procedure was lower in the remimazolam group as compared to the midazolam group (10.9% vs 31.3%, P = .016). No statistically significant differences were observed between the 2 groups regarding hemodynamic fluctuations, incidence of hypoxemia, and cough response during the procedure, as well as postoperative recall, willingness to undergo reexamination, and other post-bronchoscopy adverse events. CONCLUSIONS: Bolus administration of remimazolam offers advantages over midazolam for deep sedation in elderly patients undergoing DFB, in terms of a higher success rate of sedation and a lower incidence of extra sleep within 6 hours after procedure, though the safety profiles of both groups were favorable.

Proteomic analysis reveals LRPAP1 as a key player in the micropapillary pattern metastasis of lung adenocarcinoma.

Objectives: Lung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival. Methods: Here, quantitative mass spectrometry was conducted for comparing protein expression profiles among various histological subtypes, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (including acinar and micropapillary [MIP] types). To determine the mechanism of MIP-associated metastasis, we identified a protein that was highly expressed in MIP. The expression of the selected highly expressed MIP protein was verified via immunohistochemical (IHC) analysis and its function was validated by an in vitro migration assay. Results: Proteomic data revealed that low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) was highly expressed in MIP group, which was confirmed by IHC. The co-expressed proteins in this study, PSMD1 and HSP90AB1, have been reported to be highly expressed in different cancers and play an essential role in metastasis. We observed that LRPAP1 promoted lung cancer progression, including metastasis, invasion and proliferation in vitro and in vivo. Conclusion: LRPAP1 is necessary for MIP-associated metastasis and is the candidate novel anti-metastasis therapeutic target.

Transcript Level and Sequence Matching Are Key Determinants of Off-Target Effects in RNAi.

Double-stranded RNA (dsRNA) pesticides, those based on RNA interference (RNAi) technology utilizing dsRNA, have shown potential for pest control. However, the off-target effects of dsRNA pose limitations to the widespread application of RNAi and raise concerns regarding potential side effects on other beneficial organisms. The precise impact and underlying factors of these off-target effects are still not well understood. Here, we found that the transcript level and sequence matching jointly regulate off-target effects of dsRNA. The much lower expressed target genes were knocked down to a lesser extent than genes with higher expression levels, and the critical sequence identity of off-target effects is approximately 80%. Moreover, off-target effects could be triggered by a contiguous matching sequence length exceeding 15 nt as well as nearly perfectly matching sequences with one or two base mismatches exceeding 19 nt. Increasing the dosage of dsRNA leads to more severe off-target effects. However, the length of mismatched dsRNA, the choice of different RNAi targets, and the location of target sites within the same gene do not affect the severity of off-target effects. These parameters can be used to guide the design of possibly selective sequences for RNAi, optimize the specificity and efficiency of dsRNA, and facilitate practical applications of RNAi for pest control.

Knockdown of the glutamate-gated chloride channel gene decreases emamectin benzoate susceptibility in the fall armyworm, Spodoptera frugiperda.

Emamectin benzoate (EB), a derivative of avermectin, is the primary insecticide used to control the fall armyworm (FAW) in China. However, the specific molecular targets of EB against FAW remain unclear. In this study, we cloned the glutamate-gated chloride channel (GluCl) gene, which is known to be a primary molecular target for avermectin. We first investigated the transcript levels of SfGluCl in FAW and found that the expression level of SfGluCl in the head and nerve cord was significantly higher than that in other tissues. Furthermore, we found that the expression level of SfGluCl was significantly higher in eggs than that in other developmental stages, including larvae, pupae, and adults. Additionally, we identified three variable splice forms of SfGluCl in exons 3 and 9 and found that their splice frequencies remained unaffected by treatment with the LC50 of EB. RNAi mediated knockdown of SfGluCl showed a significant reduction of 42% and 65% after 48 and 72 h of dsRNA feeding, respectively. Importantly, knockdown of SfGluCl sifgnificantly reduced LC50 and LC90 EB treatment induced mortality of FAW larvae by 15% and 44%, respectively, compared to the control group feeding by dsEGFP. In contrast, there were no significant changes in the mortality of FAW larvae treated with the control insecticides chlorantraniliprole and spinetoram. Finally, molecular docking simulations revealed that EB bound to the large amino-terminal extracellular domain of SfGluCl by forming five hydrogen bonds, two alkyl hydrophobic interactions and one salt bridge. These findings strongly suggest that GluCl may serve as one of the molecular targets of EB in FAW, shedding light on the mode of action of this important insecticide.

Elucidating the Associated Biological Function and Clinical Significance of RHOJ Expression in Urothelial Carcinoma.

Urothelial cancer, a common urinary system malignancy, often presents treatment challenges due to metastasis and chemotherapy side effects. Angiogenesis, crucial for tumor growth, has become a target for drug development. This study explores the expression, prognostic value, and clinical correlation of RHOJ in the TCGA BLCA, GSE31684, and GSE32894 datasets. We identify common differentially expressed genes across these databases and utilize g:Profiler and Cytoscape ClueGO for functional assessment. Further, we perform a gene set enrichment analysis (GSEA) using Hallmark gene sets and use the imsig package for immune cell infiltration analysis. Our analysis indicates that RHOJ expression levels significantly impact survival rates, tumor progression, and immune response in urothelial tumors. High RHOJ expression correlated with poor prognosis, advanced disease stages, and an increase in monocyte population within the tumor microenvironment. This aligns with current literature indicating a key role of immune infiltration in bladder cancer progression and treatment response. Moreover, the GSEA and imsig results further suggest a potential mechanistic link between RHOJ expression and immune-related pathways. Considering the increasing emphasis on immunotherapeutic strategies in bladder cancer management, our findings on RHOJ's potential as a diagnostic biomarker and its association with immune response open new avenues for therapeutic interventions.

A Performance Improvement for Indoor Positioning Systems Using Earth's Magnetic Field.

Although most indoor positioning systems use radio waves, such as Wi-Fi, Bluetooth, or RFID, for application in department stores, exhibition halls, stations, and airports, the accuracy of such technology is easily affected by human shadowing and multipath propagation delay. This study combines the earth's magnetic field strength and Wi-Fi signals to obtain the indoor positioning information with high availability. Wi-Fi signals are first used to identify the user's area under several kinds of environment partitioning methods. Then, the signal pattern comparison is used for positioning calculations using the strength change in the earth's magnetic field among the east-west, north-south, and vertical directions at indoor area. Finally, the k-nearest neighbors (KNN) method and fingerprinting algorithm are used to calculate the fine-grained indoor positioning information. The experiment results show that the average positioning error is 0.57 m in 12-area partitioning, which is almost a 90% improvement in relation to that of one area partitioning. This study also considers the positioning error if the device is held at different angles by hand. A rotation matrix is used to convert the magnetic sensor coordinates from a mobile phone related coordinates into the geographic coordinates. The average positioning error is decreased by 68%, compared to the original coordinates in 12-area partitioning with a 30-degree pitch. In the offline procedure, only the northern direction data are used, which is reduced by 75%, to give an average positioning error of 1.38 m. If the number of reference points is collected every 2 m for reducing 50% of the database requirement, the average positioning error is 1.77 m.

Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia.

Introduction: MicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways. Methods: To understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA. Results: Although individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment. Conclusion: Collectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions.

Rectal prolapse in a 30-year-old bladder stone male patient: A case report.

BACKGROUND: Rectal prolapse occurs most commonly in children and middle-aged and elderly women and is relatively rare in young men and is occasionally caused by bladder stones. Severe rectal prolapse, bilateral hydronephrosis, and renal insufficiency caused by bladder stones are rare in a 30-year-old man. CASE SUMMARY: We report the case of a 30-year-old male patient with cerebral palsy who presented with a large bladder stone that resulted in severe rectal prolapse, bilateral hydronephrosis, and renal insufficiency. Following a definitive diagnosis, the bladder stone was successfully removed, and his kidney function returned to normal. We assessed the patient's nutritional status and stone composition and concluded that the main cause was malnutrition. CONCLUSION: Rectal prolapse is a rare clinical manifestation of bladder stones, particularly in young adults. Cerebral palsy patients are a vulnerable group in society because of their intellectual disabilities and communicative impairments. Accordingly, besides taking care of their daily diet, abnormal signs in their bodies should receive the doctors' attention in a timely manner.

Enantio- and Diastereoselective Synthesis of Chiral Tetrasubstituted α-Amino Allenoates Bearing a Vicinal All-Carbon Quaternary Stereocenter with Dual-Copper-Catalysis.

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are of importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions of 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording chiral tetrasubstituted α-amino allenoates bearing a vicinal all-carbon quaternary stereocenter in high yields (up to 99 % yield) with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to >20 : 1 dr). Importantly, the stereodivergent synthesis of the products was realized by the asymmetric γ-addition reaction and the Grignard reagent promoted epimerization. Moreover, the dual-copper-catalyzed γ-addition reactions were smoothly applied to a gram-scale reaction and adopted to introduce chiral tetrasubstituted allenyl moieties into bioactive molecules. Mechanistic experiments and density functional theory (DFT) calculations demonstrated that the asymmetric γ-addition reactions were catalyzed by double chiral copper catalysts.

Cu-Catalyzed Asymmetric Kinetic Boron Conjugate Addition of γ-Substituted α,ß-Unsaturated γ-Lactams.

Chiral α,ß-unsaturated γ-lactams bearing simple γ- substituents are found in biologically active molecules and natural products, however, their synthesis still remains difficult. Herein, we report an efficient kinetic resolution (KR) of γ-substituted α,ß-unsaturated γ-lactams via a Cu-catalyzed asymmetric boron conjugate addition, which also leads to the efficient synthesis of chiral ß-hydroxy-γ-lactams with ß,γ-stereogenic carbon centers. The KR proceeded smoothly with a wide range of γ-alkyl or aryl substituted substrates including those bearing aromatic heterocycles and different N-protected substrates in up to 347 of s value. Their highly versatile transformations, synthetic utility in biologically active molecules, and inhibitory activities against cisplatin-sensitive ovarian cancer cell A2780 have also been demonstrated. Differing from the well-known mechanism involving Cu-B species in Cu-catalyzed boron conjugate additions, our mechanistic studies using density functional theory (DFT) calculations and experiments indicate that a Lewis acid CuI -catalyzed mechanism is the likely pathway in the catalytic reaction.

Understanding the Migration Intention of Psychological Home in Cyberspace.

The present study views the personal main page on social media as a psychological home in cyberspace, since they have identical characteristics. Many young people share their lives on social media. However, a backlash is triggered among young people when parents start to use social media and attempt to participate in their children's online activities, causing young users to migrate social media platforms. This study introduced two concepts of psychological home, self-disclosure and psychological ownership, and the research purpose aims to investigate the relationships between self-disclosure, psychological ownership, and migration intention based on the expectation-disconfirmation theory. A survey research method was used in the study. A total of 561 samples were collected through online questionnaires, and SmartPLS 4.0 was applied for analysis. The results reveal that (1) parental involvement in social media has a positive relationship with dissatisfaction; (2) disconfirmation of psychological ownership and disconfirmation of self-disclosure have a negative relationship with dissatisfaction; (3) the greater the users' dissatisfaction with social media is, the greater the intention to migrate social medias.

Control efficacy and joint toxicity of metaflumizone mixed with chlorantraniliprole or indoxacarb against the fall armyworm, Spodoptera frugiperda.

BACKGROUND: The fall armyworm (FAW), Spodoptera frugiperda is the main destructive pest of grain crops, and has led to substantial economic losses worldwide. Chemical pesticides are the most effective way to manage FAW. Here, a laboratory test using an artificial diet-incorporated assay was conducted to determine the toxicity of five insecticides and the joint effect of the binary combination insecticides to FAW larvae. A field plot test using foliar spray was carried out to assess the control efficacy of metaflumizone mixed with chlorantraniliprole or indoxacarb against FAW. RESULTS: The bioassay results showed that metaflumizone had a stronger insecticidal effect than indoxacarb toward FAW larvae. Furthermore, the mixture of metaflumizone and chlorantraniliprole in a volume ratio of 3:7 had the strongest synergistic effect against FAW, with a co-toxicity coefficient (CTC) of 317.18. The best synergistic effect for mixtures of metaflumizone and indoxacarb was observed at a 1:9 volume ratio, with a CTC of 185.98. However, there was an antagonistic effect of metaflumizone mixed with emamectin benzoate and with lufenuron, because the co-toxic factor was less than -20 at volume ratios of 8:2 and 9:1, respectively. According to the results of the field trial, metaflumizone mixed with chlorantraniliprole or indoxacarb at a 50% reduction of the application rate can effectively control FAW with efficacy ranging from 77.73% to 94.65% 1-7 days postapplication. CONCLUSION: Overall, our findings suggest that metaflumizone and its binary combination insecticides can be utilized in FAW integrated pest management programs. © 2022 Society of Chemical Industry.

The safety and efficacy of alfentanil combined with midazolam in fiberoptic bronchoscopy sedation: A randomized, double-blind, controlled trial.

Sedation is recommended by most guidelines to be offered to all patients undergoing diagnostic flexible bronchoscopy (DFB) without contraindications, and the most commonly reported regimen is midazolam in combination with a short-acting opioid (fentanyl or alfentanil) to provide both sedative and antitussive effects. However, the optimal dose or ideal regimen of the combination therapy with midazolam and opioids has not yet been found. So this randomized, double-blinded clinical trial was designed and registered (ChiCTR2100049052) to assess the safety and efficacy of midazolam combined with different doses of alfentanil in DFB sedation. Our study showed that relative high doses of alfentanil (10-25 µg/kg) combined with a fixed low dose of midazolam can markedly reduce hemodynamic fluctuations, cough reactions, patients' discomforts, and improve their satisfaction in a dose-dependent manner during DFB, with no significant increase in the desaturation risks.

Effects of Personality Traits Concerning Media Use Decisions on Fear of Missing Out and Social Media Use Behavior.

We could view the phenomenon of fear of missing out (FoMO) as a dilemma of too many choices about social media. Although there are already various studies on FoMO, there is still a lack of studies on what personality traits concerning media use decisions will contribute to FoMO or how FoMO mediates these personality traits and people's social media use behavior, and, thus, corresponding negative emotions. This study explored the causes of FoMO in a FoMO moderated mediation model using maximizing tendency before the choice was made, social comparison orientation when making choices, and regrets tendency after the choice was made. The results showed that (1) there is a non-significant influence between maximizing tendency and FoMO, (2) regret tendency is a positive influence on FoMO, (3) social comparison orientation is a positive influence on FoMO, (4) FoMO is a positive influence on the compulsive use of social media and surveillance use of social media, (5) FoMO exhibited a full mediating effect on the relationship between regret tendency and social media surveillance use, (6) FoMO exhibited a full mediating effect on the relationship between social comparison orientation and social media compulsive use.

Cost-Effective Fitting Model for Indoor Positioning Systems Based on Bluetooth Low Energy.

Bluetooth Low Energy (BLE) is a positioning technology that is commonly used in indoor positioning systems (IPS) such as shopping malls or underground parking lots, because of its low power consumption and the low cost of Bluetooth devices. It also maintains high positioning accuracy. Since the cost of BLE itself is low, it has now been used in larger environments such as parking lots or shopping malls for a long time. However, it is necessary to configure a large number of devices in the environment to obtain accurate positioning results. The most accurate method of using signal strength for positioning is the signal pattern-matching method. The positioning result is compared through a database with the overheads of time and labor costs, since the amount of data will be proportional to the size of the environment for BLE-IPS. A planar model that conforms to the signal strength in the environment was generated, wherein the database comparison method is replaced by an equation solution, to improve various costs but diminish the positioning accuracy. In this paper, we propose to further replace the planar model with a cost-effective fitting model to both save costs and improve positioning accuracy. The experimental results demonstrate that this model can effectively reduce the average positioning error in distance by 31%.