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1.
Biomed Pharmacother ; 175: 116421, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719708

RESUMO

Tofacitinib can effectively improve the clinical symptoms of rheumatoid arthritis (RA) patients. In this current study, a recombinant human CYP2C19 and CYP3A4 system was operated to study the effects of recombinant variants on tofacitinib metabolism. Moreover, the interaction between tofacitinib and myricetin was analyzed in vitro. The levels of M9 (the main metabolite of tofacitinib) was detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The findings revealed that 11 variants showed significant changes in the levels of M9 compared to CYP3A4.1, while the other variants didn't reveal any remarkable significances. Compared with CYP2C19.1, 11 variants showed increases in the levels of M9, and 10 variants showed decreases. Additionally, it was demonstrated in vitro that the inhibition of tofacitinib by myricetin was a non-competitive type in rat liver microsomes (RLM) and human liver microsomes (HLM). However, the inhibitory mechanism was a competitive type in CYP3A4.18, and mixed type in CYP3A4.1 and .28, respectively. The data demonstrated that gene polymorphisms and myricetin had significant effects on the metabolism of tofacitinib, contributing to important clinical data for the precise use.

2.
Chemphyschem ; : e202400332, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690751

RESUMO

A series of NaGd1-x-ySiO4: y Dy3+ - x Eu3+ phosphors were synthesized by a high-temperature solid-phase method. The optimal doping ion concentration of Dy3+ ions for this phosphor was determined to be 1% from the emission spectra. The energy transfer between Dy3+ and Eu3+ ions at 351 nm was investigated by photoluminescence spectra and fluorescence decay curves. At the excitation wavelengths of 275 nm, 351 nm, 366 nm, and 394 nm, a change from yellow to white to red light can be realized by adjusting the doping concentration of Eu/Dy ions. Particularly, by testing the temperature-dependent fluorescence spectrum of the phosphor, it can be found that the luminous intensity of the phosphor is as high as 96% when 394 nm excitation is employed at 413 K. It was the maximum at this temperature comparing with other phosphors as far as we know. The color coordinate values show that the NaGd1-x-ySiO4: x Dy3+ - y Eu3+ phosphors are very close to the white light color coordinates (x = 0.33, y = 0.33) under 351 nm excitation. Meanwhile, the correlated color temperature is between 5062 - 7104 K. These results indicate that this phosphor is a promising candidate for high-quality WLED.

3.
Curr Mol Med ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38726778

RESUMO

BACKGROUND: Gastric Cancer (GC) has become one of the most important causes of cancer-related deaths worldwide due to its intractability. Studying the mechanisms of gastric carcinogenesis, recurrence, and metastasis, and searching for new therapeutic targets have become the main directions of today's gastric cancer research. Lactate is considered a metabolic by-product of tumor aerobic glycolysis, which can regulate tumor development through various mechanisms, including cell cycle regulation, immunosuppression, and energy metabolism. However, the effects of genes related to lactate metabolism on the prognosis and tumor microenvironmental characteristics of GC patients are unknown.

Method: In this study, we have collected gene expression data of gastric cancer from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes in gastric cancer using the "Limma" software package.

Result: 76 differentially expressed lactate metabolism-related genes were screened, and then the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were employed that identified 8 genes, constructed Lactate Metabolism-related gene signals (LMRs), and verified the reliability of the prognostic risk mapping by using TCGA training set and TCGA internal test set. Finally, the functional enrichment analysis was employed to identify the molecular mechanism.

Conclusion: Eight lactate metabolism-related genes were constructed into a new predictive signal that better predicted the overall survival of gastric cancer patients and can guide clinical decisions for more precise and personalized treatment.

4.
Sci Total Environ ; : 173168, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740193

RESUMO

Green space exposure provides greater beneficial effects on residents compared to unnatural spaces, commonly referred to as "gray spaces". However, during rapid urbanization, gray spaces expand more quickly than green spaces, often encroaching upon and overtaking these natural environments. This unchecked growth leads to detrimental impacts on the human habitat and overall environmental quality. Consequently, it is essential to meticulously assess the spatial and temporal patterns of residents' exposure levels, as well as to thoroughly investigate the underlying driving mechanisms behind these changes. This study used population-weighted exposure level measurements to assess gray and green space exposure in Chinese cities in the early 21st Century (2000-2019). Additionally, the Gray-Green space Exposure Ratio (GER) was calculated, and the spatiotemporal driving mechanism of GER by each factor was analyzed by geostatistical modeling. The results show that gray space exposure is generally increasing in China, especially in eastern parts of China. The probability of exposure to gray spaces exceeds that of green spaces in some high urbanization rate cities. This trend will continue, albeit at a slower rate. Urban sprawl, built-up area density, and increased electricity consumption were the main drivers of rising GER, whereas greenspace integrity contributed to lower GER; the driving mechanisms for GER changes were spatiotemporal heterogeneous. This study provides a reliable reference for restoring the green space exposure to promote the living environment constructing and residents' access to nature.

5.
Pestic Biochem Physiol ; 201: 105863, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685216

RESUMO

The whitefly Bemisia tabaci poses a significant threat to various crops and ornamental plants and causes severe damage to the agricultural industry. Over the past few decades, B. tabaci has developed resistance to several pesticides, including imidacloprid. Therefore, elucidating the mechanism that leads to insecticide detoxification is very important for controlling B. tabaci and managing whitefly resistance to neonicotinoid insecticides. Among insect detoxification enzymes, glutathione S-transferase (GST) is an important phase II detoxification enzyme that helps detoxify exogenous toxic substances. In this study, we cloned the BtGSTz1 gene and observed that its expression level was greater in imidacloprid-resistant populations than sensitive populations of B. tabaci. By silencing BtGSTz1 via RNA interference, we found a significant increase in the mortality of imidacloprid-resistant B. tabaci. Additionally, prokaryotic expression and in vitro metabolism studies revealed that the recombinant BtGSTz1 protein could metabolize 36.36% of the total imidacloprid, providing direct evidence that BtGSTz1 plays a crucial role in the detoxification of imidacloprid. Overall, our study elucidated the role of GSTs in physiological activities related to insecticide resistance, which helps clarify the resistance mechanisms conferred by GSTs and provides useful insights for sustainable integrated pest management.


Assuntos
Glutationa Transferase , Hemípteros , Resistência a Inseticidas , Inseticidas , Neonicotinoides , Nitrocompostos , Hemípteros/efeitos dos fármacos , Hemípteros/genética , Hemípteros/metabolismo , Animais , Neonicotinoides/farmacologia , Neonicotinoides/metabolismo , Nitrocompostos/farmacologia , Nitrocompostos/metabolismo , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Inseticidas/farmacologia , Inseticidas/metabolismo , Resistência a Inseticidas/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Interferência de RNA , Imidazóis/farmacologia , Imidazóis/metabolismo
6.
CNS Neurosci Ther ; 30(3): e14579, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38497532

RESUMO

AIMS: This study aimed to investigate the resting-state functional connectivity and topologic characteristics of brain networks in patients with diabetic optic neuropathy (DON). METHODS: Resting-state functional magnetic resonance imaging scans were performed on 23 patients and 41 healthy control (HC) subjects. We used independent component analysis and graph theoretical analysis to determine the topologic characteristics of the brain and as well as functional network connectivity (FNC) and topologic properties of brain networks. RESULTS: Compared with HCs, patients with DON showed altered global characteristics. At the nodal level, the DON group had fewer nodal degrees in the thalamus and insula, and a greater number in the right rolandic operculum, right postcentral gyrus, and right superior temporal gyrus. In the internetwork comparison, DON patients showed significantly increased FNC between the left frontoparietal network (FPN-L) and ventral attention network (VAN). Additionally, in the intranetwork comparison, connectivity between the left medial superior frontal gyrus (MSFG) of the default network (DMN) and left putamen of auditory network was decreased in the DON group. CONCLUSION: DON patients altered node properties and connectivity in the DMN, auditory network, FPN-L, and VAN. These results provide evidence of the involvement of specific brain networks in the pathophysiology of DON.


Assuntos
Diabetes Mellitus , Doenças do Nervo Óptico , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
7.
J Agric Food Chem ; 72(10): 5153-5164, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427964

RESUMO

Being a destructive pest worldwide, the whitefly Bemisia tabaci has evolved resistance to neonicotinoid insecticides. The third-generation neonicotinoid dinotefuran has commonly been applied to the control of the whitefly, but its underlying mechanism is currently unknown. On the base of our transcriptome data, here we aim to investigate whether the cytochrome P450 CYP6EM1 underlies dinotefuran resistance in the whitefly. Compared to the susceptible strain, the CYP6EM1 gene was found to be highly expressed in both laboratory and field dinotefuran-resistant populations. Upon exposure to dinotefuran, the mRNA levels of CYP6EM1 were increased. These results demonstrate the involvement of this gene in dinotefuran resistance. Loss and gain of functional studies in vivo were conducted through RNAi and transgenic Drosophila melanogaster assays, confirming the role of CYP6EM1 in conferring such resistance. In a metabolism assay in vitro, the CYP6EM1 protein could metabolize 28.11% of dinotefuran with a possible dinotefuran-dm-NNO metabolite via UPLC-QTOF/MS. Docking of dinotefuran to the CYP6EM1 protein showed a good binding affinity, with an energy of less than -6.0 kcal/mol. Overall, these results provide compelling evidence that CYP6EM1 plays a crucial role in the metabolic resistance of B. tabaci to dinotefuran. Our work provides new insights into the mechanism underlying neonicotinoid resistance and applied knowledge that can contribute to sustainable control of a global pest such as whitefly.


Assuntos
Guanidinas , Hemípteros , Inseticidas , Animais , Hemípteros/metabolismo , Drosophila melanogaster/metabolismo , Resistência a Inseticidas/genética , Neonicotinoides/metabolismo , Nitrocompostos/metabolismo , Inseticidas/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo
8.
J Pharm Biomed Anal ; 243: 116079, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38471255

RESUMO

This aim of the work was to establish an acceptable sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentrations of iguratimod (IGR) and its metabolite M2 in rats, and to further investigate the effect of fluconazole on the pharmacokinetics of IGR and M2. The mobile phase consisted of acetonitrile and water with 0.1% formic acid, was used to separate IGR, M2 and internal standard (IS) fedratinib on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) with the flow rate of 0.4 mL/min. Positive ion mode and multiple reaction monitoring (MRM) were used to construct the quantitative analysis. The calibration standard of IGR and M2 covered 2-10000 and 1-1000 ng/mL respectively, with the lower limit of quantification (LLOQ) as 2 ng/mL and 1 ng/mL respectively. In addition, selectivity, recovery, accuracy, precision, matrix effect and stability of the method validation program were well accepted in this work. Subsequently, this approach was used to assess the effect of fluconazole on the pharmacokinetics of IGR and M2 in rats. In the presence of 20 mg/kg fluconazole (experimental group), we found the main pharmacokinetic parameters were significantly altered when compared with 2.5 mg/kg IGR alone (control group). Among them, AUC(0-∞) and Cmax of IGR in the experimental group was 1.43 and 1.08 times higher than that of the control group, respectively. Moreover, we also found that the other main pharmacokinetic parameters of M2 had no significant changes, except t1/2z and Tmax. In conclusion, fluconazole significantly altered the main pharmacokinetics of IGR and M2 in rats. It implys that we should pay more attention to the adverse reaction of IGR when the concomitant use of fluconazole and IGR occur in the future clinical practice.


Assuntos
Cromonas , Espectrometria de Massa com Cromatografia Líquida , Sulfonamidas , Espectrometria de Massas em Tandem , Ratos , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Fluconazol , Interações Medicamentosas , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes
9.
J Agric Food Chem ; 72(8): 4464-4475, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38376143

RESUMO

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.


Assuntos
Camellia sinensis , Camellia sinensis/genética , Camellia sinensis/metabolismo , Teobromina/metabolismo , Cafeína/metabolismo , Folhas de Planta/metabolismo , Chá/metabolismo , Fatores de Transcrição/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
10.
PLoS Genet ; 20(2): e1011163, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38377137

RESUMO

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.


Assuntos
Hemípteros , Inseticidas , Receptores Nicotínicos , Animais , Receptores Nicotínicos/genética , Inseticidas/farmacologia , Hemípteros/genética , Drosophila melanogaster , Neonicotinoides/farmacologia , Mutação
11.
Sci Rep ; 14(1): 4552, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402285

RESUMO

Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.


Assuntos
Infarto do Miocárdio , Tomografia de Coerência Óptica , Humanos , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Vasos Retinianos/diagnóstico por imagem , Retina/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem
12.
Environ Res ; 250: 118520, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38401683

RESUMO

The sedentary and less active lifestyle of modern college students has a significant impact on the physical and mental well-being of the college community. Campus Green Spaces (GSs) are crucial in promoting physical activity and improving students' health. However, previous research has focused on evaluating campuses as a whole, without considering the diverse spatial scenarios within the campus environment. Accordingly, this study focused on the young people's residential scenario in university and constructed a framework including a comprehensive set of objective and subjective GSs exposure metrics. A systematic, objective exposure assessment framework ranging from 2D (GSs areas), and 2.5D (GSs visibility) to 3D (GSs volume) was innovatively developed using spatial analysis, deep learning technology, and unmanned aerial vehicle (UAV) measurement technology. Subjective exposure metrics incorporated GSs visiting frequency, GSs visiting duration, and GSs perceived quality. Our cross-sectional study was based on 820 university students in Nanjing, China. Subjective measures of GSs exposure, physical activity, and health status were obtained through self-reported questionnaires. The Generalized Linear Model (GLM) was used to evaluate the associations between GSs exposure, physical activity, and perceived health. Physical activity and social cohesion were considered as mediators, and path analysis based on Structural Equation Modeling (SEM) was used to disentangle the mechanisms linking GSs exposure to the health status of college students. We found that (1) 2D indicator suggested significant associations with health in the 100m buffer, and the potential underlying mechanisms were: GSs area → Physical activity → Social cohesion → Physical health → Mental health; GSs area → Physical activity → Social cohesion → Mental health. (2) Subjective GSs exposure indicators were more relevant in illustrating exposure-response relationships than objective ones. This study can clarify the complex nexus and mechanisms between campus GSs, physical activity, and health, and provide a practical reference for health-oriented campus GSs planning.

13.
J Nat Med ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409483

RESUMO

Atherosclerosis is a cardiovascular disease, accounting for the most common mortality cause worldwide. Notoginsenoside R1 (NGR1) is a characteristic saponin of Radix notoginseng that exhibits anti-inflammatory and antioxidant effects while modulating lipid metabolism. Evidence suggests that NGR1 exerts cardioprotective, neuroprotective, and anti-atherosclerosis effects. However, underlying NGR1 mechanisms alleviating atherosclerosis (AS) have not been examined. This study used a network pharmacology approach to construct the drug-target-disease correlation and protein-protein interaction (PPI) network of NGR1 and AS. Moreover, functional annotation and pathway enrichment analyses deciphered the critical biological processes and signaling pathways potentially regulated by NGR1. The protective effect of NGR1 against AS and the underlying mechanism(s) was assessed in an atherogenic apolipoprotein E-deficient (ApoE-/-) mice in vivo and an oxidized low-density lipoprotein (ox-LDL)-induced macrophage model in vitro. The network pharmacology and molecular docking analyses revealed that NGR1 protects against AS by targeting the NLRP3/caspase-1/IL-1ß pathway. NGR1 reduced foam cell formation in ox-LDL-induced macrophages and decreased atherosclerotic lesion formation, serum lipid metabolism, and inflammatory cytokines in AS mice in vivo. Therefore, NGR1 downregulates the NLRP3 inflammasome complex gene expression of NLRP3, caspase-1, ASC, IL-1ß, and IL-18, in vivo and in vitro.

14.
BMC Chem ; 18(1): 37, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378603

RESUMO

Broad-spectrum histone deacetylase inhibitors (HDACi) have excellent anti-tumor effects, such as abexinostat, which was a novel oral HDACi that was widely used in clinical treatment. The purpose of this study was to establish a rapid and reliable method for the detection of abexinostat concentrations in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The mobile phase we used was acetonitrile and 0.1% formic acid, and the internal standard (IS) was givinostat. Selective reaction monitoring (SRM) was used for detection with ion transitions at m/z 397.93 → 200.19 for abexinostat and m/z 422.01 → 186.11 for givinostat, respectively. The intra-day and inter-day precision of abexinostat were less than 11.5% and the intra-day and inter-day accuracy ranged from - 10.7% to 9.7% using this method. During the analysis process, the stability of the test sample was reliable. In addition, the recovery and matrix effects of this method were within acceptable limits. Finally, the method presented in this paper enabled accurate and quick determination of abexinostat levels in rat plasma from the pharmacokinetic study following gavage at a dose of 8.0 mg/kg abexinostat.

15.
Pest Manag Sci ; 80(2): 341-354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37688583

RESUMO

BACKGROUND: Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a major agricultural insect pest that causes severe economic losses worldwide. Several insecticides have been applied to effectively control this key pest. However, owing to the indiscriminate use of chemical insecticides, B. tabaci has developed resistance against these chemical compounds over the past several years. RESULTS: From 2019 to 2021, 23 field samples of B. tabaci were collected across China. Twenty species were identified as the Mediterranean 'Q' type (MED) and three were identified as MED/ Middle East-Asia Minor 1 mixtures. Subsequently, resistance of the selected populations to different insecticides was evaluated. The results showed that 13 populations developed low levels of resistance to abamectin. An overall upward trend in B. tabaci resistance toward spirotetramat, cyantraniliprole and pyriproxyfen was observed. In addition, resistance to thiamethoxam remained low-to-moderate in the 23 field populations. CONCLUSION: These findings suggest that the overall resistance of the field-collected B. tabaci populations has shown an upward trend over the years in China. We believe our study can provide basic data to support integrated pest management and insecticide resistance management of field B. tabaci in China. © 2023 Society of Chemical Industry.


Assuntos
Hemípteros , Inseticidas , Animais , Inseticidas/farmacologia , Resistência a Inseticidas , China , Tiametoxam
16.
Pest Manag Sci ; 80(2): 910-921, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37822143

RESUMO

BACKGROUND: Understanding the trade-offs between insecticide resistance and the associated fitness is of particular importance to sustainable pest control. One of the most devastating pest worldwide, the whitefly Bemisia tabaci, has developed resistance to various insecticides, especially the neonicotinoid group. Although neonicotinoid resistance often is conferred by P450s-mediated metabolic resistance, the relationship between such resistance and the associated fitness phenotype remains largely elusive. By gene cloning, quantitative reverse transcription (qRT)-PCR, RNA interference (RNAi), transgenic Drosophila melanogaster, metabolism capacity in vitro and 'two sex-age stage' life table study, this study aims to explore the molecular role of a P450 gene CYP4CS5 in neonicotinoid resistance and to investigate whether such resistance mechanism carries fitness costs in the whitefly. RESULTS: Our bioassay tests showed that a total of 13 field-collected populations of B. tabaci MED biotype displayed low-to-moderate resistance to thiamethoxam and clothianidin. Compared to the laboratory susceptible strain, we then found that an important P450 CYP4CS5 was remarkably upregulated in the field resistant populations. Such overexpression of CYP4CS5 had a good match with the resistance level among the whitefly samples. Further exposure to the two neonicotinoids resulted in an increase in CYP4CS5 expression. These results implicate that overexpression of CYP4CS5 is closely correlated with thiamethoxam and clothianidin resistance. RNAi knockdown of CYP4CS5 increased mortality of the resistant and susceptible populations after treatment with thiamethoxam and clothianidin in bioassay, but obtained an opposite result when using a transgenic line of D. melanogaster expressing CYP4CS5. Metabolic assays in vitro revealed that CYP4CS5 exhibited certain capacity of metabolizing thiamethoxam and clothianidin. These in vivo and in vitro assays indicate an essential role of CYP4CS5 in conferring thiamethoxam and clothianidin resistance in whitefly. Additionally, our life-table analysis demonstrate that the field resistant whitefly exhibited a prolonged development time, shortened longevity and reduced fecundity compared to the susceptible, suggesting an existing fitness cost as a result of the resistance. CONCLUSION: Collectively, in addition to the important role of CYP4CS5 in conferring thiamethoxam and clothianidin resistance, this resistance mechanism is associated with fitness costs in the whitefly. These findings not only contribute to the development of neonicotinoids resistance management strategies, but also provide a new target for sustainable whitefly control. © 2023 Society of Chemical Industry.


Assuntos
Guanidinas , Hemípteros , Inseticidas , Tiazóis , Animais , Tiametoxam/metabolismo , Drosophila melanogaster/genética , Nitrocompostos/farmacologia , Nitrocompostos/metabolismo , Oxazinas , Neonicotinoides/farmacologia , Neonicotinoides/metabolismo , Inseticidas/farmacologia , Inseticidas/metabolismo , Animais Geneticamente Modificados , Resistência a Inseticidas/genética
17.
Front Endocrinol (Lausanne) ; 14: 1239883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38093968

RESUMO

Background: Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work. Methods: A genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction. Hypothyroidism was linked to 22,687 cases and 440,246 controls. For hyperthyroidism, there were 3545 cases and 459,388 controls. A total of 3751 cases and 372016 controls were included in the genetic data for CMM from UK Biobank (http://www.nealelab.is/uk-biobank) (the Dataset: ieu - b - 4969). Among them, inverse variance weighting (IVW) is the main MR Analysis method for causality assessment. MR-Egger method, MR Pleiotropic residual and outlier test (MR-PRESSO), and simple and weighted median (VM) were used to supplement the IVW method. Sensitivity analyses, mainly Cochran's Q test, leave-one-out analysis, and MR Egger intercept test were performed to assess the robustness of the outcomes. Results: The two-sample MR Analysis results revealed a negative correlation between genetically predicted hypothyroidism and the probability of CMM (OR=0.987, 95%CI =0.075-0.999, p=0.041). The supplemental MR Analysis did not reveal any statistically significant differences, although the direction of the effect sizes for the other approaches was consistent with the IVW effect sizes. The results of the causal analysis were relatively robust, according to a sensitivity analysis. The risk of CMM was unaffected by hyperthyroidism (p>0.05). No correlation between CMM and thyroid dysfunction was seen in the reverse MR analysis. Conclusion: Although the magnitude of the causal association is weak and further investigation of the mechanism of this putative causal relationship is required, our findings imply that hypothyroidism may be a protective factor for CMM.


Assuntos
Hipertireoidismo , Hipotireoidismo , Melanoma , Neoplasias Cutâneas , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Melanoma/epidemiologia , Melanoma/genética , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética
18.
J Pain Res ; 16: 4049-4069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38054110

RESUMO

Background: Acupuncture is considered an important means of analgesic, which has been widely used in chronic pelvic pain syndrome (CPPS) management and treatment in recent years, published a large number of related documents. However, the relevant literature in this field has not been summarized and quantitatively analyzed. Therefore, this study aims to analyze the hotspots and predicting future research trends of acupuncture on pelvic pain syndrome. Methods: Search for the relevant publications of the web of science database from 2000 to 2022 about the treatment of acupuncture on chronic pelvic pain syndrome. The Citespace software and VosViewer software are used to analyze the visualization of the countries, institutions, authors, keywords and references and references in the literature. Results: A total of 173 publications were included. The annual number of essays gradually showed an overall growth trend over time. Medicine magazine is the most published journal in this field. J UROLOGY and Acupunct Med are the most cited journals and the most influential magazines; The most active and influential country is China, and the most produced institutions are Beijing University of Chinese Medicine; The most produced authors are Liu Zhishun. The most cited and most influential authors are Nickel JC and Armour M; keywords and cited reference analysis show that the quality of life, mechanism research, alternative medicine and electro-acupuncture will be the scientific hotspot of acupuncture treatment for chronic pelvic pain syndrome. Conclusion: This study shows that acupuncture on CPPS is increasingly valued and recognized. The future research hotspots will focus on the effects and mechanisms. In the future, more high-quality animal basic research will be required to explore the exact mechanism of acupuncture on CPPS. In addition, different parameters of acupuncture such as electric-acupuncture, stimulating frequency, duration and strength are also the focus of future research. More clinical trials are required to verify its safety and effectiveness.

19.
Pestic Biochem Physiol ; 196: 105635, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945266

RESUMO

The whitefly, Bemisia tabaci, comes up high metabolic resistance to most neonicotinoids in long-term evolution, which is the key problem of pest control. UGT glycosyltransferase, as a secondary detoxification enzyme, plays an indispensable role in detoxification metabolism. In this study, UGT inhibitors, 5-nitrouracil and sulfinpyrazone, dramatically augmented the toxic damage of neonicotinoids to B. tabaci. A UGT named UGT353G2 was identified in whitefly, which was notably up-regulated in resistant strain (3.92 folds), and could be induced by most neonicotinoids. Additionally, the using of RNA interference (RNAi) suppresses UGT353G2 substantially increased sensitivity to neonicotinoids in resistant strain. Our results support that UGT353G2 may be involved in the neonicotinoids resistance of whitefly. These findings will help further verify the functional role of UGTs in neonicotinoid resistance.


Assuntos
Hemípteros , Inseticidas , Animais , Neonicotinoides/farmacologia , Neonicotinoides/metabolismo , Inseticidas/farmacologia , Inseticidas/metabolismo , Hemípteros/metabolismo , Nitrocompostos/farmacologia , Nitrocompostos/metabolismo , Resistência a Inseticidas/genética , Difosfato de Uridina/metabolismo
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