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Chronic stress significantly elevates the expression levels of various neurotransmitters in the tumour microenvironment, thereby promoting the cell growth and metastasis of lung adenocarcinoma (LUAD). However, the role of chronic stress in the progression of LUAD remains unclear. In this study, we found that chronic restraint stress increases the levels of the neurotransmitter acetylcholine (ACh), and the α5-nicotinic acetylcholine receptor (α5-nAChR) and decreased fragile histidine triad (FHIT) expression in vivo. Crucially, the increased ACh levels promoted LUAD cell migration and invasion via modulation of the α5-nAChR/DNA methyltransferase 1 (DNMT1)/FHIT axis. In a chronic unpredictable stress (CUMS) mouse model, chronic stress promotes tumour development, accompanied by changes in α5-nAChR, DNMT1, FHIT, and vimentin. Together, these findings reveal a novel chronic stress-mediated LUAD signalling pathway: chronic stress enforces lung adenocarcinoma cell invasion and migration via the ACh/α5-nAChR/FHIT axis, which could be a potential therapeutic target for chronic stress-related LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Receptores Nicotínicos , Animales , Ratones , Nicotina/farmacología , Acetilcolina/farmacología , Receptores Nicotínicos/genética , Transducción de Señal , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Trypsin is one of the most diverse and widely studied protease hydrolases. However, the diversity and characteristics of the Trypsin superfamily of genes have not been well understood, and their role in insecticide resistance is yet to be investigated. In this study, a total of 342 Trypsin genes were identified and classified into seven families based on homology, characteristic domains and phylogenetics in Anopheles sinensis, and the LY-Domain and CLECT-Domain families are specific to the species. Four Trypsin genes, (Astry2b, Astry43a, Astry90, Astry113c) were identified to be associated with pyrethroid resistance based on transcriptome analyses of three field resistant populations and qRT-PCR validation, and the knock-down of these genes significantly decrease the pyrethroid resistance of Anopheles sinensis based on RNAi. The activity of Astry43a can be reduced by five selected insecticides (indoxacarb, DDT, temephos, imidacloprid and deltamethrin); and however, the Astry43a could not directly metabolize these five insecticides, like the trypsin NYD-Tr did in earlier reports. This study provides the overall information frame of Trypsin genes, and proposes the role of Trypsin genes to insecticide resistance. Further researches are necessary to investigate the metabolism function of these trypsins to insecticides.
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Anopheles , Resistencia a los Insecticidas , Insecticidas , Piretrinas , Tripsina , Animales , Anopheles/genética , Anopheles/efectos de los fármacos , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Tripsina/genética , Tripsina/metabolismo , Piretrinas/farmacología , Filogenia , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Malaria/transmisión , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismoRESUMEN
OBJECTIVES: The CHRNΑ5 gene, which encodes the α5-nicotinic acetylcholine receptor (α5-nAChR), is related to lung cancer and nicotine addiction. Smoking is closely related to the immunosuppressive effect of macrophages. CD47, a phagocytosis checkpoint in macrophages, is a therapeutic target in various cancer types. Nevertheless, the relationship between α5-nAChR and CD47 in lung cancer is still unclear. METHODS AND RESULTS: The present study showed that α5-nAChR-mediated CD47 expression via STAT3 signaling, consequently leading to tumor progression and immune suppression in lung adenocarcinoma (LUAD). α5-nAChR expression was correlated with STAT3 expression, CD47 expression, smoking status and poor prognosis of LUAD in vivo. In vitro, α5-nAChR expression mediated the phosphorylation of STAT3, and phosphorylated STAT3 bound to the CD47 promoter and mediated CD47 expression. Downregulation of α5-nAChR and/or CD47 significantly reduced cell proliferation, migration, invasion, stemness and IL-10 expression, but increased TNF-α expression and phagocytosis of macrophages in LUAD. Furthermore, α5-nAChR/CD47 signaling contributed to the growth of subcutaneous xenograft tumors and liver metastasis of tumors in mice. CONCLUSION: The α5-nAChR/STAT3/CD47 axis contributed to the progression and immune escape of lung cancer and may be a potential target for LUAD immunotherapy.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Receptores Nicotínicos , Humanos , Animales , Ratones , Nicotina/farmacología , Antígeno CD47/genética , Antígeno CD47/metabolismo , Receptores Nicotínicos/metabolismo , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/genética , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
To observe the therapeutic effect of PD-1 inhibitors on driver-gene mutation negative advanced non-squamous non-small cell lung cancer (nsNSCLC) and the role of the AGEs-RAGE system in the disease, provide more reliable treatment for future nsNSCLC patients. In this study, we selected 130 nsNSCLC patients admitted between January 2021 and April 2022 were selected as the study subjects, 61 of whom received pemetrexed plus carboplatin (control group) and 69 received PD-1 inhibitors, pemetrexed and carboplatin (research group). The clinical efficacy and adverse reactions of the two groups were compared, and the prognostic survival time was calculated. The results show that two groups were not statistically different in objective response rate (ORR) and incidence of adverse reactions, but the disease control rate (DCR) was higher in the research group (P<0.05). Besides, the median progression-free survival (PFS) was prolonged in the research group compared with the control group (P<0.05). In addition, changes in the levels of T lymphocyte subsets, AGEs and RAGE before and after treatment were detected, and the relationship between AGEs-RAGE and the therapeutic effect of PD-1 inhibitors was analyzed. The research group also showed higher CD3+, CD4+ and lower CD8+, AGEs and RAGE levels than the control group after treatment (P<0.05). Finally, we found that in addition, the efficacy of the study group was inversely related to AGEs and RAGE levels (P<0.05). With these results, we concluded that PD-1 inhibitors are effective in the treatment of driver-gene mutation negative advanced nsNSCLC, and the AGEs-RAGE system may provide a more reliable guarantee for the treatment outcomes of patients in the future.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pemetrexed/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carboplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , MutaciónRESUMEN
Unraveling the origin of Helmholtz capacitance is of paramount importance for understanding the interfacial structure and electrostatic potential distribution of electric double layers (EDL). In this work, we combined the methods of ab initio molecular dynamics and classical molecular dynamics and modeled electrified Cu(100)/electrolyte and graphene/electrolyte interfaces for comparison. It was proposed that the Helmholtz capacitance is composed of three parts connected in series: the usual solvent capacitance, water chemisorption induced capacitance, and Pauling repulsion caused gap capacitance. We found the Helmholtz capacitance of graphene is significantly lower than that of Cu(100), which was attributed to two intrinsic factors. One is that graphene has a wider gap layer at interface, and the other is that graphene is less active for water chemisorption. Finally, based on our findings, we provide suggestions for how to increase the EDL capacitance of graphene-based materials in future work, and we also suggest that the new understanding of the potential distribution across the Helmholtz layer may help explain some experimental phenomena of electrocatalysis.
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BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, and the diagnosis and treatment of AS have been limited because its pathogenesis is still unclear. Pyroptosis is a proinflammatory type of cell death that plays an important role in the immune system. However, the relationship between pyroptosis genes and AS has never been elucidated. METHODS: GSE73754, GSE25101, and GSE221786 datasets were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis-related genes (DE-PRGs) were identified by R software. Machine learning and PPI networks were used to screen key genes to construct a diagnostic model of AS. AS patients were clustered into different pyroptosis subtypes according to DE-PRGs using consensus cluster analysis and validated using principal component analysis (PCA). WGCNA was used for screening hub gene modules between two subtypes. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used for enrichment analysis to elucidate underlying mechanisms. The ESTIMATE and CIBERSORT algorithms were used to reveal immune signatures. The connectivity map (CMAP) database was used to predict potential drugs for the treatment of AS. Molecular docking was used to calculate the binding affinity between potential drugs and the hub gene. RESULTS: Sixteen DE-PRGs were detected in AS compared to healthy controls, and some of these genes showed a significant correlation with immune cells such as neutrophils, CD8 + T cells, and resting NK cells. Enrichment analysis showed that DE-PRGs were mainly related to pyroptosis, IL-1ß, and TNF signaling pathways. The key genes (TNF, NLRC4, and GZMB) screened by machine learning and the protein-protein interaction (PPI) network were used to establish the diagnostic model of AS. ROC analysis showed that the diagnostic model had good diagnostic properties in GSE73754 (AUC: 0.881), GSE25101 (AUC: 0.797), and GSE221786 (AUC: 0.713). Using 16 DE-PRGs, AS patients were divided into C1 and C2 subtypes, and these two subtypes showed significant differences in immune infiltration. A key gene module was identified from the two subtypes using WGCNA, and enrichment analysis suggested that the module was mainly related to immune function. Three potential drugs, including ascorbic acid, RO 90-7501, and celastrol, were selected based on CMAP analysis. Cytoscape showed GZMB as the highest-scoring hub gene. Finally, molecular docking results showed that GZMB and ascorbic acid formed three hydrogen bonds, including ARG-41, LYS-40, and HIS-57 (affinity: -5.3 kcal/mol). GZMB and RO-90-7501 formed one hydrogen bond, including CYS-136 (affinity: -8.8 kcal/mol). GZMB and celastrol formed three hydrogen bonds, including TYR-94, HIS-57, and LYS-40 (affinity: -9.4 kcal/mol). CONCLUSIONS: Our research systematically analyzed the relationship between pyroptosis and AS. Pyroptosis may play an essential role in the immune microenvironment of AS. Our findings will contribute to a further understanding of the pathogenesis of AS.
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Espondilitis Anquilosante , Humanos , Simulación del Acoplamiento Molecular , Piroptosis/genética , Ácido Ascórbico , Biología ComputacionalRESUMEN
Fractional carbon dioxide (CO2) laser combined with subcision has been widely used for the clinical treatment, but the efficacy of the combined therapy on three types of atrophic acne scars remains unreported. This retrospective study analyzed the clinical data of 413 patients with atrophic acne scars, treated with fractional CO2 laser combined with subcision in the combined group and with fractional CO2 laser in the control group. The treatment efficacy was evaluated by the Investigator's Global Assessment (IGA) and the Échelle d'évaluation clinique des cicatrices d'acné (ECCA). We reported adverse reactions such as erythema, lump, skin sensitivity, acne recurrence, and hyperpigmentation that occurred in both treatment groups. The treatment efficiency of the combined group was significantly higher than that of the control group (P < 0.001). Among the three subtypes of atrophic acne scars, the ECCA scores in the combined group of boxcar-type and rolling-type scars after treatment were lower than those in the control group (P = 0.041, P < 0.001, respectively), and no statistical difference in scores between the two groups for icepick-type scars was seen (P = 0.062). There was no statistical difference in adverse reactions between the two groups (P = 0.361). Fractional CO2 laser combined with subcision is more effective than fractional CO2 laser in the treatment of boxcar-type and rolling-type scars, but there is no significant difference in the treatment of icepick-type scars.
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Acné Vulgar , Láseres de Gas , Humanos , Cicatriz/etiología , Cicatriz/radioterapia , Cicatriz/cirugía , Dióxido de Carbono , Estudios Retrospectivos , Láseres de Gas/efectos adversos , Acné Vulgar/complicaciones , AtrofiaRESUMEN
Passion fruit (Passilora edulis, family Passifloraceae.) is an economically important fruit crop in many tropical and subtropical regions worldwide. It is widely planting in southern China, and in greenhouses throughout the country. In Mar 2022, symptoms of a viral-like infection were observed on the leaves of passion fruit plants in a 3-hectare greenhouse complex in Hohhot, China. Chlorotic lesions were observed on leaves of two vines of passion fruit and symptomatic leaves developed chlorotic spots, followed by systemic leaf chlorosis and necrosis. Dark ringed spots emerged on the surface of matured fruits (Figure 1). To confirm infectivity, mechanical transmission of the virus was performed by grinding leaves from two symptomatic passion fruit vines in 0.1M phosphate buffer pH 7, and the resulting two samples were each used to rub-inoculate carborundum-dusted leaves of three healthy passion fruit seedlings. Newly emerging leaves of inoculated plants developed mild mosaic symptoms 30-days after inoculation. Three samples from each of the two original symptomatic plants and two samples from each inoculated seedling tested positive using a Passiflora latent virus (PLV) ELISA Kit (Creative Diagnostics, USA). To further confirm the virus identity, total RNA from leaf samples from one of the original greenhouse symptomatic plants and one of the inoculated seedlings were extracted using an TaKaRa MiniBEST Viral RNA Extraction Kit (Takara, Japan). The two RNA samples were subjected to reverse transcription-polymerase chain reaction (RT-PCR) tests with virus specific primers PLV-F (5'-ACACAAAACTGCGTGTTGGA-3') and PLV-R (5'-CAAGACCCACCTACCTCAGTGTG-3') (Cho et al., 2020). RT-PCR products of the expected 571 bp were obtained from both the original greenhouse sample and inoculated seedling. Amplicons were cloned into the pGEM-T Easy Vector, and two clones per sample were Sanger sequenced bidirectionally (Sangon Biotech, China), and the sequence of one clone from one of the original symptomatic sample was uploaded to NCBI (GenBank OP320922.1). This accession had 98% nucleotide sequence identity with a PLV isolate from Korea (GenBank: LC556232.1). RNA extracts from two asymptomatic samples tested negative for PLV with both ELISA and RT-PCR tests. We also tested the original symptomatic sample for common occurring passion fruit viruses, including passion fruit woodiness virus (PWV), cucumber mosaic virus (CMV), east asian passiflora virus (EAPV), telosma mosaic virus (TeMV), papaya leaf curl Guangdong virus (PaLCuGdV), and the RT-PCR results were negative for those viruses. However, based on the systemic leaf chlorosis and necrosis symptoms, we cannot preclude a mixed infestation of other viruses. PLV affects fruit quality and has high potential to reduce market value. To our knowledge, this is the first report of PLV in China, which could provide a reference basis to PLV identification, prevention and control. Acknowledgments This research was carried out with the support of Inner Mongolia Normal University High-level Talents Scientific Research Startup Project (Grant no. 2020YJRC010). Supplementary material Figure 1. Mottle, leaf distortion, puckering symptoms on old leaf (A), mild puckering symptom on young leaf (B), and ring-striped spots symptoms on fruit (C) of the PLV infected passion fruit plant in China.
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We have engineered brewer's yeast as a general platform for de novo synthesis of diverse ß-lactam nuclei starting from simple sugars, thereby enabling ready access to a number of structurally different antibiotics of significant pharmaceutical importance. The biosynthesis of ß-lactam nuclei has received much attention in recent years, while rational engineering of non-native antibiotics-producing microbes to produce ß-lactam nuclei remains challenging. Benefited by the integration of heterologous biosynthetic pathways and rationally designed enzymes that catalyze hydrolysis and ring expansion reactions, we succeeded in constructing synthetic yeast cell factories which produce antibiotic cephalosporin C (CPC, 170.1 ± 4.9 µg/g DCW) and the downstream ß-lactam nuclei, including 6-amino penicillanic acid (6-APA, 5.3 ± 0.2 mg/g DCW), 7-amino cephalosporanic acid (7-ACA, 6.2 ± 1.1 µg/g DCW) as well as 7-amino desacetoxy cephalosporanic acid (7-ADCA, 1.7 ± 0.1 mg/g DCW). This work established a Saccharomyces cerevisiae platform capable of synthesizing multiple ß-lactam nuclei by combining natural and artificial enzymes, which serves as a metabolic tool to produce valuable ß-lactam intermediates and new antibiotics.
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Saccharomyces cerevisiae , beta-Lactamas , Antibacterianos , Vías Biosintéticas , Saccharomyces cerevisiae/metabolismo , beta-Lactamas/metabolismoRESUMEN
OBJECTIVES: An accurate and rapid diagnosis is crucial for the appropriate treatment of pulmonary tuberculosis (TB). This study aims to develop an artificial intelligence (AI)-based fully automated CT image analysis system for detection, diagnosis, and burden quantification of pulmonary TB. METHODS: From December 2007 to September 2020, 892 chest CT scans from pathogen-confirmed TB patients were retrospectively included. A deep learning-based cascading framework was connected to create a processing pipeline. For training and validation of the model, 1921 lesions were manually labeled, classified according to six categories of critical imaging features, and visually scored regarding lesion involvement as the ground truth. A "TB score" was calculated based on a network-activation map to quantitively assess the disease burden. Independent testing datasets from two additional hospitals (dataset 2, n = 99; dataset 3, n = 86) and the NIH TB Portals (n = 171) were used to externally validate the performance of the AI model. RESULTS: CT scans of 526 participants (mean age, 48.5 ± 16.5 years; 206 women) were analyzed. The lung lesion detection subsystem yielded a mean average precision of the validation cohort of 0.68. The overall classification accuracy of six pulmonary critical imaging findings indicative of TB of the independent datasets was 81.08-91.05%. A moderate to strong correlation was demonstrated between the AI model-quantified TB score and the radiologist-estimated CT score. CONCLUSIONS: The proposed end-to-end AI system based on chest CT can achieve human-level diagnostic performance for early detection and optimal clinical management of patients with pulmonary TB. KEY POINTS: ⢠Deep learning allows automatic detection, diagnosis, and evaluation of pulmonary tuberculosis. ⢠Artificial intelligence helps clinicians to assess patients with tuberculosis. ⢠Pulmonary tuberculosis disease activity and treatment management can be improved.
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Inteligencia Artificial , Tuberculosis Pulmonar , Adulto , Anciano , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Tuberculosis Pulmonar/diagnóstico por imagenRESUMEN
Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.
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Esclerodermia Localizada , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Femenino , Humanos , Neuroimagen , Radiografía , Esclerodermia Localizada/diagnóstico por imagen , Esclerodermia Localizada/patología , Piel/patologíaRESUMEN
Using polyethylene wax (PW) as the coating matrix, the lambda-cyhalothrin-PW nanosuspoemulsion (LC-PW) with a particle size of 80-150nm was prepared through high-speed stirring, hot melt emulsification and ultrasonic dispersion. The formulation and composition of the LC-PW were optimized, the morphology of the LC-PW was analyzed by dynamic light scattering (DLS) and TEM, and the structure of the LC-PW was characterized by UV and IR. The anti-photolysis test showed that LC-PW had a good anti-photolysis performance. Furthermore, LC-PW could sustainably release Lambda-cyhalothrin, which was pH- and temperature dependent. The insecticidal activity analysis in the greenhouse indicated that the toxic strength between LC-PW and LC-SC (lambda-cyhalothrin-suspension concentrate) to Mythimna separata was similar within the same concentration ranges tested, but the insecticidal duration of LC-PW was significantly longer than LC-SC. Thus, the new type of LC-PW with the properties of anti-photolysis and controlled release is suitable for application in the field as a better insecticide.
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Insecticidas , Piretrinas , Concentración de Iones de Hidrógeno , Nitrilos , Polietilenos , TemperaturaRESUMEN
This work investigated the effects of thermal processing methods commonly used in the dairy industry and prolonged treatment at different temperatures on the denaturation, microstructure, and functional properties of whey proteins (WP) from goat milk. The complete denaturation of WP was observed in goat milk treated at 85°C for 30 min, and at a higher temperature (>85°C), a considerable amount of WP was easily denatured. The low temperature, long time treatment had the least effect on the secondary structure, whereas ultra-high temperature treatment had the greatest effect, and the amount of regular structures decreased gradually with prolonged time. The most serious morphological damage occurred after treatment at 85°C for 30 min, which was consistent with the denaturation results. This result indicated that the denaturation degree, particle size, surface hydrophobicity, and microstructure had a strong influence on the functional properties of WP from goat milk after heat treatment. The heat treatment of goat milk at 65°C for 30 min and 85°C for 15 s increased the particle size, turbidity, zeta potential, and surface hydrophobicity of WP, and these increases ensured that the WP had a good emulsifying activity index, water-holding capacity, oil-holding capacity, foaming capacity, and foam stability. This study simulated the heat treatment conditions used in actual production, aiming to provide a theoretical basis for industry.
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Cabras , Calefacción , Leche/química , Proteína de Suero de Leche/química , Animales , Femenino , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Conformación Proteica , Desnaturalización ProteicaRESUMEN
Globally, alpine glaciers hold a large quantity of dissolved organic matter (DOM) and are headwaters of numerous rivers supporting downstream heterotrophic metabolism. However, it remains unclear how glacial coverage and distance from the glacial terminus affect the fate of DOM. Here, we elucidate DOM variability in glacial-fed streams on the Tibetan Plateau using field sampling and bioincubation experiments and compare our findings with the existing literature. We found that dissolved organic carbon, DOM absorption a(254), DOM aromaticity, and the relative abundance of lignin compounds in glacial-fed streams and rivers all increased with increasing distance from the glacial terminus and with decreasing glacial coverage. We also found that contribution of protein-like components, the relative abundance of aliphatic compounds, and DOM biolability increased with increasing glacial coverage and with decreasing distance from the glacial terminus. The ratio of glacial coverage to the logarithmic transformed distance from the glacial terminus was better than that of actual glacial coverage and distance from the glacial terminus in tracing the variability of glacial-fed stream DOM. Microbes in surface ice can produce biolabile DOM that is exported downstream with meltwater. This glacial-fed stream and river DOM is an important source of the highly bioavailable material fueling downstream heterotrophic activity.
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Ecosistema , Ríos , Carbono , Cubierta de Hielo , TibetRESUMEN
A method for detecting the organophosphorus pesticides residue and aflatoxins in China herbal tea has been developed by UPLC-MS/MS coupled with vortex-assisted dispersive liquid-liquid microextraction (DLLME). The extraction conditions for vortex-assisted DLLME extraction were optimized using single-factor experiments and response surface design. The optimum conditions for the experiment were the pH 5.1, 347 µL of chloroform (extraction solvent) and 1614 µL of acetonitrile (dispersive solvent). Under the optimum conditions, the targets were good linearity in the range of 0.1 µg/Lâ»25 µg/L and the correlation coefficient above 0.9998. The mean recoveries of all analytes were in the ranged from 70.06%â»115.65% with RSDs below 8.54%. The detection limits were in the range of 0.001 µg/Lâ»0.01µg/L. The proposed method is a fast and effective sample preparation with good enrichment and extraction efficiency, which can simultaneously detect pesticides and aflatoxins in China herbal tea.
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Aflatoxinas/análisis , Plaguicidas/análisis , Tés de Hierbas/análisis , Cromatografía Líquida de Alta Presión , Límite de Detección , Microextracción en Fase Líquida , Solventes/química , Espectrometría de Masas en TándemRESUMEN
PURPOSE: To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action. METHODS: Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V-FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC. RESULTS: BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells. CONCLUSION: This study provides help to elucidate the translational potential of the in vitro results to be used for further in vivo studies on human glioma using animal or human subjects. The mechanistic pathway studied in this report could be helpful in explaining the mode of action of these classes of natural products.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Puntos de Control del Ciclo Celular/efectos de los fármacos , Dicumarol/farmacología , Glioma/tratamiento farmacológico , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glioma/patología , Humanos , Microscopía FluorescenteRESUMEN
OBJECTIVE: To observe the imaging features for chronic whiplash alar ligament injury in elderly patients and to provide an effective diagnostic method for long-term neck pain and headaches due to alar ligament injury in elderly patients. METHODS: A total of 134 elderly patients, who engaged in the work or activities related to whiplash motion and suffered from chronic neck pain, were enrolled for the study. All patients were performed comprehensive health examination (CT, MR, ultrasound and laboratory examination) and high resolution PDWI. The patients were divided into 2 groups according to the results of comprehensive health examination: a clear etiology group(CE group, n=96) and an unknown etiology group(UE group, n=38). Th e characteristics of PDWI signal in the ligament were analyzed between the 2 groups. RESULTS: Th e anatomy and signal characteristics of the alar ligament were clearly displayed by high resolution PDWI. Th e alar ligaments were effectively displayed by oblique coronal image. In the CE group, 7 patients (7/96) showed the positive sign of ligament injured, while 21 (21/38) patients showed positive sign of ligament injured in the UE group (P<0.01). Chronic whiplash ligament injury was proved to be the reason for long-term neck pain and headaches in 15.7% patients. CONCLUSION: Th e whiplash injury of alar ligament is an important reason for chronic neck pain in elderly patients. High resolution PDWI is an effective method to evaluate the image features of alar ligament and can provide an accurate diagnosis for chronic neck pain and headaches caused by the alar ligament whiplash injury.
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Ligamentos/patología , Imagen por Resonancia Magnética , Lesiones por Latigazo Cervical/diagnóstico , Anciano , Vértebras Cervicales , Dolor Crónico , Fascia , HumanosRESUMEN
Nano pesticides offer an effective means of improving the bioavailability of pesticide due to their excellent solubility and wettability, superior foliar adhesion, and permeability to target insects. By using high-speed homogenization and ultrasonic dispersion technology, an emamectin-sodium alginate nano-formulation (EB@SA) with a particle size ranging from 30 to 50 nm was successfully fabricated using electrostatic self-assembly. The microscopic morphology and structure of EB@SA were further analyzed through transmission electron microscopy, dynamic light scattering, infrared spectroscopy, and 1H NMR. The photolysis resistance behavior of EB@SA demonstrated an improved anti-photolysis ability more than double that of conventional formulations while also exhibiting good sustained-release properties. Not only does EB@SA maintain the inherent insecticidal toxicity of emamectin benzoate (EB), but it also significantly prolongs its insecticidal duration. At a concentration of 20 mg/L, the lethality rate against Armyworms remains above 70 % over a period of 16 days compared to <50 % for general emamectin emulsifiable concentrate. Furthermore, EB@SA greatly enhances the systemic translocation of EB in corn plants by exhibiting favorable bidirectional systemic translocation characteristics. This research presents an efficient and environmentally friendly pesticide nano-formulation that can be effectively utilized for field pest control.
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Alginatos , Insecticidas , Fotólisis , Ivermectina/farmacología , Ivermectina/química , Insecticidas/farmacologíaRESUMEN
Background and purpose: Significant differences in the outcomes observed in patients with acute ischemic stroke (AIS) have led to research investigations for identifying the predictors. In this retrospective study, we aimed to investigate the relationship of different clinical and imaging factors with the prognosis of AIS. Materials and methods: All clinical and imaging metrics were compared between the good and poor prognosis groups according to the modified Rankin Scale (mRS) score at 90 days after discharge. Clinical factors included gender, age, NIHSS scores at admission, and other medical history risk factors. Imaging markers included the lesion's size and location, diffusion, and perfusion metrics of infarction core and peripheral regions, and the state of collateral circulation. Spearman's correlations were analyzed for age and imaging markers between the different groups. The Chi-square test and Cramer's V coefficient analysis were performed for gender, collateral circulation status, NIHSS score, and other stroke risk factors. Results: A total of 89 patients with AIS were divided into the good (mRS score ≤ 2) and poor prognosis groups (mRS score ≥ 3). There were differences in NIHSS score at the admission; relative MK (rMK), relative MD (rMD), relative CBF (rCBF) of the infarction core; relative mean transit time (rMTT), relative time to peak (rTTP), and relative CBF (rCBF) of peripheral regions; and collateral circulation status between the two groups (p < 0.05). Among them, the rMK of infarction lesions had the strongest correlation with the mRS score at 90 days after discharge (r = 0.545, p < 0.001). Conclusion: Perfusion and diffusion metrics could reflect the microstructure and blood flow characteristics of the lesion, which were the key factors for the salvage ability and prognosis of the infarction tissue. The characteristics of the infarction core and peripheral regions have different effects on the outcomes. Diffusion of infarction core has strong relations with the prognosis, whereas the time metrics (MTT, TTP) were more important for peripheral regions. MK had a more significant association with prognosis than MD. These factors were the primary markers influencing the prognosis of cerebral infarction patients.
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Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.