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Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.
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Sistema Enzimático do Citocromo P-450 , Resistência a Inseticidas , Inseticidas , Nitrilas , Piretrinas , Spodoptera , Animais , Piretrinas/farmacologia , Piretrinas/toxicidade , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Nitrilas/toxicidade , Nitrilas/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Inseticidas/farmacologia , Inseticidas/toxicidade , Resistência a Inseticidas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Interferência de RNA , Inativação Metabólica , Larva/efeitos dos fármacos , Larva/genéticaRESUMO
Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.
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Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Inibidores da Bomba de Prótons , Humanos , Refluxo Laringofaríngeo/fisiopatologia , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/terapia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/terapia , Refluxo Gastroesofágico/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento , Estilo de VidaRESUMO
The genome-level features are crucial genetic resources for species identification and phylogenetic analysis. Here, the complete mitochondrial genome of Aphidius colemani Viereck 1912 (Hymenoptera: Braconidae: Aphidiinae) was sequenced, determined and analyzed. The circular genome is 16,372 bp in length with an overall base composition of 38.9% for A, 46.2% for T, 6.7% for C, and 8.2% for G. The mitochondrial genome of A. colemani contained 13 protein-coding genes that initiated by the ATN codon, 22 transfer RNA genes, two ribosomal RNA genes (rRNAs), and a control region (CR). It shared the same gene arrangement patterns that occurred in two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY with Aphidius gifuensis. Phylogenetic analyses using Bayesian inference and Maximum-likelihood methods supported that the two species of Aphidiinae formed a clade and sister to other subfamilies of Braconidae.
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Cistos do Sistema Nervoso Central , Diabetes Insípido , Diabetes Mellitus , Neoplasias Hipofisárias , Humanos , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico por imagem , Cistos do Sistema Nervoso Central/cirurgia , Diabetes Insípido/complicações , Diabetes Insípido/diagnóstico , Dor no Peito/etiologia , Imageamento por Ressonância MagnéticaRESUMO
Quantum dot light-emitting diodes (QLEDs) are an emerging class of optoelectronic devices with a wide range of applications. However, there still exist several drawbacks preventing their applications, including long-term stability, electron leakage, and large power consumption. To circumvent the difficulties, QLEDs based on a self-assembled hole transport layer (HTL) with reduced device complexity are proposed and demonstrated. The self-assembled HTL is prepared from poly[3-(6-carboxyhexyl)thiophene-2,5-diyl] (P3HT-COOH) solution in N,N-dimethylformamide (DMF) forming a well-ordered monolayer on an indium-tin-oxide (ITO) anode. The P3HT-COOH monolayer has a smaller HOMO band offset and a sufficiently large electron barrier with respect to the CdSe/ZnS quantum dot (QD) emission layer, and thus it is beneficial for hole injection into and electron leakage blocking from the QD layer. Interestingly, the QLEDs exhibit an excellent conversion efficiency (97%) in turning the injected electron-hole pairs into light emission. The performance of the resulting QLEDs possesses a low turn-on voltage of +1.2 V and a maximum external quantum efficiency of 25.19%, enabling low power consumption with high efficiency. Additionally, those QLEDs also exhibit excellent long-term stability without encapsulation with over 90% luminous intensity after 200 days and superior durability with over 70% luminous intensity after 2 h operation under the luminance of 1000 cd m-2. The outstanding device features of our proposed QLEDs, including low turn-on voltage, high efficiency, and long-term stability, can advance the development of QLEDs toward facile large-area mass production and cost-effectiveness.
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This study proposed and tested a model adapted from Biggs' 3P model that quantifies the behaviors of students who completed MOOCs (Massive Open Online Courses) in order to design intervention measures for low retention rates. Psychomotor domain data from 300 MOOC learners was analyzed in a covariance-based structural equation model (CB-SEM) to analyze the direct and indirect effects of various factors. Results show the basic psychological needs theory (BPNT) in the presage stage significantly positively correlated with engagement in the process stage. Meanwhile, the process stage exhibited a significantly positive correlation with the product stage, representing persistence intention (PI). Furthermore, a full mediation effect was observed among the presage, process, and product stages. The mediating effect demonstrates that higher student engagement leads to more positive exertion on BNPT and PI to complete the course. Moreover, results show bolstering students' behavioral, emotional, and cognitive engagement strengthens their PIs.
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Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 µg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems.
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Microplásticos , Poluentes do Solo , Plásticos , Cádmio , Solo , Esgotos , Poluentes do Solo/análiseRESUMO
The complicated contamination of microplastics (MPs) and heavy metals in sludge has garnered substantial attention in recent years; however, research on the behavior of MPs loading of heavy metals in sludge after sludge treatment methods is limited. Four representative sludge treatment methods were selected herein: anaerobic digestion, thermal drying, thermal hydrolysis (TH), and aerobic composting. Before and after sludge treatment, the chemical bonding of MPs, cadmium (Cd) adsorption properties, and metabolic changes in the microbial community succession was analyzed, and the factors influencing differences in Cd sorption by sludge MPs were explored. The results revealed that Cd adsorption by MPs occurs as multilayer physical adsorption that can be well fitted by Freundlich isotherms. Compared with the other three treatments, TH led to the most significant effect on the chemical bonding properties of the MPs, with a more than two-fold increase in C-O single bonds and CO double bonds, as well as adsorption of the highest amount of Cd at 767 µg/g. In addition, sludge conductivity and water content also affected Cd sorption capacity, with correlation coefficients of 0.405 and -0.384. Pedobacter, Flavobacterium, Lysobacter, and Sphingobacterium in the sludge presented a high degree of coupling with adsorption capacity, it was inferred that the above dominant species of bacteria may affect the adsorption of Cd by microplastics through the production of extracellular enzyme forms.
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Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio/química , Microplásticos , Plásticos/química , Esgotos , Água , Poluentes Químicos da Água/análiseRESUMO
Environmental pollution by microplastics (MPs) is a significant and complex global issue. Existing MPs identification methods have demonstrated significant limitations such as low resolution, long imaging time, and limited particle size analysis. New and improved methods for MPs identification are topical research areas, with machine learning (ML) algorithms proven highly useful in recent years. Critical literature reviews on the latest developments in this area are limited. This study closes this gap and summarizes the progress made over the last 10 years in using ML algorithms for identifying and quantifying MPs. We identified diverse combinations of ML methods and fundamental techniques for MPs identification, such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and near-infrared spectroscopy. The most widely used ML model is the support vector machine, which effectively improves the conventional analysis method for spectral quality defects and improves detection accuracy. Artificial neural network models exhibit improved recognition effects, with shorter detection times and better MPs recognition efficiency. Our review demonstrates the potential of ML in improving the identification and quantification of MPs.
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Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Aprendizado de Máquina , Plásticos/química , Poluentes Químicos da Água/análiseRESUMO
Multilevel and flexible nonvolatile memory (NVM) is a promising candidate for data storage in next-generation devices but its high bias and low mobility of conducting channels are often its drawbacks. In this study, we demonstrate a low bias of smaller than 0.1 V and a high-mobility graphene layer as a conducting channel for flexible optoelectronic NVM based on a composite thin film of indium-based MOF-derived InCl3 and 4,4-oxydiphthalic anhydride (odpta), Na[In3(odpt)2(OH)2(H2O)2](H2O)4, and reduced graphene oxide (rGO). The optoelectronic NVM device can be encoded and erased optically by ultraviolet (UV) light and visible light, respectively. Our device also achieves memory states over 192 (6-bit storage) distinct levels, which can emerge as mass data storage. It also shows an excellent endurance of write-erase cycles under irradiation with a laser of varying wavelengths, the mechanical stability of more than 1000 bending cycles, and stable retention for longer than 10â¯000 s. These results open an alternative route for developing low bias and innovative optoelectronic technologies.
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BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.
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Células Acinares , Endorribonucleases , Animais , Humanos , Camundongos , Células Acinares/metabolismo , Ácido Araquidônico/metabolismo , Proteínas de Transporte/metabolismo , Endorribonucleases/metabolismo , Fibrose , Radioisótopos de Gálio , Camundongos Knockout , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteínas Serina-Treonina Quinases , Tripsina/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-ß) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-ß, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.
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Stone buildings exposed to natural environment inevitably subject to various factors. Among which, biodeterioration caused by bacteria, fungi, algae, lichen, and moss is widespread. The long-term cumulative effect of biodeterioration will lead to irreversible changes in the aesthetic characteristics, physical and chemical properties of stone buildings. Therefore, it is necessary to control the biodeterioration of stone buildings. Here, we summarized four traditional methods including heat shock treatments, laser and ultraviolet radiation, application of biocides, and presented typical examples. We analyzed several emerging techniques, such as synergistic effect of physical and chemical methods, plant extracts and nanomaterials biocides, and reviewed their advantages, disadvantages as well as applicability. Aiming to provide a reference for the research of biodeterioration prevention and conservation of stone buildings, we discussed the preventive methods for biodeterioration of stone building and the assessment methods to test the effects of such methods, and prospected the future research direction.
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Líquens , Raios Ultravioleta , Bactérias , Meio Ambiente , FungosRESUMO
Dynamic changes in the tumor-associated fibroblast activation protein (FAP) expression in tumors of different stages may be helpful for prognostic evaluation and treatment response monitoring, making this protein a promising surveillance biomarker for timely diagnosis of malignant tumors and effective planning of patient care. To prospectively verify the diagnostic efficacy value of the developed FAP tracers, [68Ga]Ga-FAPtp and [68Ga]Ga-Alb-FAPtp-01, dynamic/static positron emission tomography (PET)/computed tomography scans were acquired for tumor-targeting studies in vivo and in comparison with the well-established clinically used tracer [68Ga]Ga-FAPI-04. The optimized rationally designed FAP-targeting PET tracer, [68Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the [68Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.
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Fibroblastos Associados a Câncer , Glioma , Radioisótopos de Gálio , Humanos , Tomografia por Emissão de Pósitrons , QuinolinasRESUMO
Male sterility refers to the phenomenon that stamens cannot grow normally and produce viable pollen grains in plants. Hybrid seed production by taking advantage of the trait of male sterility is an effective and quick strategy to increase crop yield. Up to date, the yield of rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and other crops has been greatly increased based on hybrid vigor utilization. Soybean (Glycine max (L.) Merr.) is a self-pollination species, artificial emasculation is not only time-consuming, but also labor-intensive and economically impracticable. So far, large scale hybrid breeding has not been performed in soybean due to the shortage of male sterile lines suitable for hybrid production. Therefore, it is urgent to identify a stable male sterile system for the rapid utilization of heterosis in soybean. In this review, we summarize the progress on the discovery of soybean genic male sterility (GMS) mutants and GMS genes. Combining with the investigation of GMS genes in Arabidopsis, rice and maize, we provide important insights into the identification and potential utilization of GMS genes in soybean in the perspective of reverse genetics.
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Glycine max/genética , Vigor Híbrido , Melhoramento Vegetal , Infertilidade das Plantas/genética , Genética ReversaRESUMO
Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.
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Fator Apoptótico 1 Ativador de Proteases/metabolismo , Proteínas de Membrana/metabolismo , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Doença Aguda , Animais , Apoptose/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Biologia Molecular/métodos , Pancreatite Crônica/genética , Proteômica/métodosRESUMO
Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.
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Fator 6 Ativador da Transcrição/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Mitocondriais/genética , Pâncreas/patologia , Pancreatite/genética , Proteína Supressora de Tumor p53/genética , Células Acinares/patologia , Fator 6 Ativador da Transcrição/genética , Adulto , Animais , Apoptose/genética , Estudos de Casos e Controles , Ceruletídeo/administração & dosagem , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Pâncreas/citologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Ativação Transcricional , Tripsina/genéticaRESUMO
OBJECTIVE: This study is aimed toward establishing a decision-making model with multiple criteria for appraisal and reimbursement to compare the attitudes of different stakeholders toward various dimensions and criteria and to evaluate the five targeted therapies (bevacizumab, cetuximab, panitumumab, aflibercept, and regorafenib) for metastatic colorectal cancer. METHOD: This study is a multi-criteria decision analysis (MCDA) using a model that includes three dimensions and nine criteria. Both the overall and individual scores of the respective targeted therapies in different dimensions and criteria were calculated. A sensitivity analysis was carried out in order to evaluate the robustness of the research results. An interview-based questionnaire survey was applied to obtain the performance information for the targeted therapies and the weights of the dimensions and criteria. RESULTS: Overall, the clinical dimension had the highest weight, followed by the economic dimension, and finally, the social dimension. In the clinical dimension, the "comparative efficacy" criterion had the highest weight; in the economic dimension, the "cost-effectiveness" criterion" was given the greatest importance; in the social dimension, the "social concern and patient needs" criterion was given more emphasis. The overall values ranked from high to low as follows: cetuximab (overall score 3.3666), bevacizumab (3.3043), panitumumab (3.2030), aflibercept (2.8923) and regorafenib (2.8366). CONCLUSIONS: A comprehensive value assessment system combining "multi-dimensional criteria," "multi-perspectives," and an "integrative assessment" is necessary to evaluate the value of medicines. The results showed not only the order of weights of different dimensions or criteria, but also the rankings of the value of the targeted therapies.
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Antineoplásicos/economia , Neoplasias Colorretais/epidemiologia , Tomada de Decisões , Custos de Medicamentos , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Análise Custo-Benefício , Pesquisas sobre Atenção à Saúde , Humanos , Terapia de Alvo Molecular/economia , Metástase Neoplásica , Estadiamento de Neoplasias , República da Coreia/epidemiologiaRESUMO
Ursodeoxycholic acid (UDCA) is a type of hydrophilic bile acid extracted from animal bile with a wide range of biological functions. The present results demonstrated that UDCA could effectively inhibit the proliferation of two human melanoma cell line (M14 and A375) with time and concentrationdependence. Following exposure to various concentrations of UDCA, M14 cells exhibited typical morphological changes and weaker ability of colony forming. Flow cytometry analysis demonstrated that UDCA could induce a decrease of mitochondrial membrane potential and an increase in reactive oxygen species (ROS) levels in M14 cells. The cell cycle was arrested in the G2/M phase, which was confirmed by the decrease of cyclindependent kinase 1 and cyclinB1 at the protein level. However, when M14 cells were treated with UDCA and ZVADFMK (caspase inhibitor) synchronously, the apoptosis rate of the cells was reduced significantly. In addition, it was demonstrated that UDCA induced apoptosis of human melanoma M14 cells through the ROStriggered mitochondrialassociated pathway, which was indicated by the increased expression of cleavedcaspase3, cleavedcaspase9, apoptotic protease activating factor1, cleavedpoly (ADPribose) polymerase 1 and the elevation of B cell lymphoma2 (Bcl2) associated X protein/Bcl2 ratio associated with apoptosis. Therefore, UDCA may be a potential drug for the treatment of human melanoma.
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Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Inibidores de Caspase/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Melanoma/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Many shipwreck events occur in the neighboring areas of Taiwan due to the volume of maritime traffic and geographical conditions around Taiwan. The oil spills from such events can be devastating for the surrounding sea and coastal areas. The government realized the importance of marine pollution prevention and enforced the Marine Pollution Control Act and the Major Marine Oil Pollution Emergency Response Plan to mitigate the impact of oil spill pollution. The T.S. Taipei shipwreck highlighted the effectiveness of the national marine pollution prevention system. Inter-departmental cooperation and collaboration with private sectors are the keys for effective response. This article is the first detailed documentation of an oil spill response for a maritime incident from the beginning to the final termination of shipwreck removal. It shows the people in Taiwan intend to collaborate with other states to make a significant contribution to marine environment conservation and sustainability.