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The massive accumulation of red mud (RM) and the abuse of antibiotics pose a threat to environment safety and human health. In this study, we synthesized RM-based Prussian blue (RM-PB) by acid solution-coprecipitation method to activate H2O2 to degrade norfloxacin, which reached about 90% degradation efficiency at pH 5 within 60 min and maintained excellent catalytic performance over a wide pH range (3-11). Due to better dispersion and unique pore properties, RM-PB exposed more active sites, thus the RM-PB/H2O2 system produced more reactive oxygen species. As a result, the removal rate of norfloxacin by RM-PB/H2O2 system was 8.58 times and 2.62 times of that by RM/H2O2 system and PB/H2O2 system, respectively. The reactive oxygen species (ROS) produced in the degradation process included ·OH, ·O2- and 1O2, with 1O2 playing a dominant role. The formation and transformation of these ROS was accompanied by the Fe(III)/Fe(II) cycle, which was conducive for the sustained production of ROS. The RM-PB/H2O2 system maintained a higher degradation efficiency after five cycles, and the material exhibited strong stability, with a low iron leaching concentration. Further research showed the degradation process was less affected by Cl-, SO42-, NO3-, and humic acids, but was inhibited by HCO3- and HPO42-. In addition, we also proposed the possible degradation pathway of norfloxacin. This work is expected to improve the resource utilization rate of RM and achieve treating waste with waste.
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Ferrocianuros , Peróxido de Hidrógeno , Norfloxacino , Humanos , Peróxido de Hidrógeno/química , Especies Reactivas de Oxígeno , Compuestos Férricos , Oxidación-ReducciónRESUMEN
Ferromagnetic debris in lubricating oil, serving as an important communication carrier, can effectively reflect the wear condition of mechanical equipment and predict the remaining useful life. In practice application, the detection signals collected by using inductive sensors contain not only debris signals but also noise terms, and weak debris features are prone to be distorted, which makes it a severe challenge to debris signature identification and quantitative estimation. In this paper, a debris signature extraction method established on segmentation entropy with an adaptive threshold was proposed, based on which five identification indicators were investigated to improve detection accuracy. The results of the simulations and oil experiment show that the proposed algorithm can effectively identify wear particles and preserve debris signatures.
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Vascular tissues serve a dual function in plants, both providing physical support and controlling the transport of nutrients, water, hormones, and other small signaling molecules. Xylem tissues transport water from root to shoot; phloem tissues transfer photosynthates from shoot to root; while divisions of the (pro)cambium increase the number of xylem and phloem cells. Although vascular development constitutes a continuous process from primary growth in the early embryo and meristem regions to secondary growth in the mature plant organs, it can be artificially separated into distinct processes including cell type specification, proliferation, patterning, and differentiation. In this review, we focus on how hormonal signals orchestrate the molecular regulation of vascular development in the Arabidopsis primary root meristem. Although auxin and cytokinin have taken center stage in this aspect since their discovery, other hormones including brassinosteroids, abscisic acid, and jasmonic acid also take leading roles during vascular development. All these hormonal cues synergistically or antagonistically participate in the development of vascular tissues, forming a complex hormonal control network.
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Proteínas de Arabidopsis , Arabidopsis , Meristema , Raíces de Plantas , Citocininas/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Hormonas/metabolismo , Agua/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Transcriptional networks are crucial to integrate various internal and external signals into optimal responses during plant growth and development. In Arabidopsis thaliana, primary root vasculature patterning and proliferation are controlled by a network centred around the basic Helix-Loop-Helix transcription factor complex, formed by TARGET OF MONOPTEROS 5 (TMO5) and LONESOME HIGHWAY (LHW), which control cell proliferation and division orientation by modulating the cytokinin response and other downstream factors. Despite recent progress, many aspects of the TMO5/LHW pathway are not fully understood. In particular, the upstream regulators of TMO5/LHW activity remain unknown. Here, using a forward genetics approach to identify new factors of the TMO5/LHW pathway, we discovered a novel function of the MYB-type transcription factor, MYB12. MYB12 physically interacts with TMO5 and dampens the TMO5/LHW-mediated induction of direct target gene expression, as well as the periclinal/radial cell divisions. The expression of MYB12 is activated by the cytokinin response, downstream of TMO5/LHW, resulting in a novel MYB12-mediated negative feedback loop that restricts TMO5/LHW activity, to ensure optimal cell proliferation rates during root vascular development.
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Proteínas de Arabidopsis , Arabidopsis , Meristema , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Raíces de Plantas/metabolismo , Retroalimentación , Transactivadores/genética , Regulación de la Expresión Génica de las Plantas , Arabidopsis/metabolismo , División Celular , Citocininas/metabolismoRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an elevated incidence of cervical cancer, and accelerated disease progression, but the underlying mechanisms are not well understood. This study aimed to investigate the relationship between HIV infection and epithelial-mesenchymal transition (EMT) in cervical cancer. METHODS: Tissue samples from HIV-positive and negative patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were analyzed for EMT-related proteins. Human cervical cancer SiHa cells were treated with HIV Tat and gp120 proteins to test their effects on EMT, migration, and invasion. RESULTS: HIV-positive patients had lower E-cadherin and cytokeratin, and higher N-cadherin and vimentin levels than HIV-negative patients. HIV Tat and gp120 proteins induced EMT, migration, and invasion in SiHa cells. Transcriptome sequencing analysis revealed that, compared to the control group, the protein-treated group showed upregulation of 22 genes and downregulation of 77 genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed the involvement of the Wnt signaling pathway in EMT. Further analysis of gene expression related to this pathway revealed upregulation of DVL1, TCF7, KRT17, and VMAC, while GSK3ß, SFRP2, and CDH1 were downregulated. Immunofluorescence assay demonstrated that HIVgp120 and Tat proteins treatment induced elevated ß-catenin expression with nuclear accumulation in SiHa cells. CONCLUSIONS: The treatment of SiHa cells with HIV Tat and gp120 proteins induces EMT and activates the Wnt/ß-catenin pathway, suggesting that the Wnt/ß-catenin pathway may play a crucial role in promoting EMT progression in cervical lesion tissues of HIV-infected patients.
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Infecciones por VIH , Neoplasias del Cuello Uterino , Femenino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Productos del Gen tat/farmacología , Transición Epitelial-Mesenquimal/fisiologíaRESUMEN
Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals' NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.
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Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Humanos , Células Asesinas NaturalesRESUMEN
Iron and manganese oxides/biochar composite materials (Fe/Mn-BC) are promising catalysts in the field of advanced oxidation. High purity chemical reagents are popular precursors for preparing Fe/Mn-BC, while the potential of low-cost natural minerals as precursors has been neglected. In this study, high-efficiency Fe/Mn-BC was synthesized by one-step pyrolysis method using hematite, phosphoromanganese, and bagasse. The synthesized Fe/Mn-BC removed 83.7% 2, 4-dichlorophenol (2, 4-DCP) within 30 min, about 8.8 and 10.6 times better than biochar (BC) and Fe/Mn complex, respectively. The removal of 2, 4-DCP in the Fe/Mn-BC + peroxydisulfate (PDS) system was influenced by catalyst dosage, PDS concentration, initial pH, organic acids, and chromium. Sulfate radical (SO4â¢-) and hydroxyl radicals (â¢OH) generated by Fe/Mn-BC-activated PDS have similar contribution to the degradation of 2,4-DCP. A possible removal mechanism of 2, 4-DCP in the Fe/Mn-BC + PDS system was proposed based on Electron Spin Resonance spectroscopy, free radical quenching experiments, X-ray photoelectron spectroscopy, X-ray diffraction, and electrochemical measurement. Fe0 and Fe(II) in Fe/Mn-BC play significant role in catalytic degradation of 2, 4-DCP at the early stage of the reaction (within 0-5 min). Then, the interaction between Mn and BC or structural Mn and structural Fe gradually became dominant in the later stage. Similarly, the electron transfer promoted by biochar also played an important role in this catalysis. This discovery provided a new strategy for developing iron and manganese oxides/biochar composite materials to activate PDS for the elimination of refractory organic pollutants.
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Aguas Residuales , Contaminantes Químicos del Agua , Manganeso/química , Carbón Orgánico/química , Óxidos/química , Hierro/química , Minerales , Fenoles , Oxidación-Reducción , Catálisis , Contaminantes Químicos del Agua/químicaRESUMEN
Acetylcholinesterase (AChE) is an essential neurotransmitter hydrolase in nervous systems of animals and its number varies among species. So far, five AChEs have been identified in the natural enemy Pardosa pseudoannulata. Here we found that Ppace1, Ppace2 and Ppace5 were highly expressed in the spider brain, among which the mRNA level of Ppace5, but not Ppace1 and Ppace2, could be up-regulated by organophosphorus insecticides at their sublethal concentrations. In spider brain, the treatment by organophosphorus insecticides at the sublethal concentrations could increase total AChE activity, although high concentrations inhibited the activity. The activity that increased from the sublethal concentration pretreatment could compensate for the activity inhibition due to subsequent application of organophosphorus insecticides at lethal concentrations, and consequently reduce the mortality of spiders. PpAChE1 and PpAChE2 were highly sensitive to organophosphorus insecticides, and their activities would be strongly inhibited by the insecticides. In contrast, PpAChE5 displayed relative insensitivity towards organophosphorus insecticides, but with the highest catalytic efficiency for ACh. That meant the up-regulation of Ppace5 under insecticide exposure was important for maintaining AChE activity in spider brain, when PpAChE1 and PpAChE2 were inhibited by organophosphorus insecticides. The study demonstrated that multiple AChEs in the spider brain worked collaboratively, with part members for maintaining AChE activity and other members responding to organophosphorus inhibition, to provide protection from organophosphorus insecticides. In fields, high concentration insecticides are often applied when ineffective controls of insect pests occur due to relative-low concentration of insecticides in last round application. This application pattern of organophosphorus insecticides provides more chances for P. pseudoannulata to survive and controlling insect pests as a natural enemy.
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Insecticidas , Arañas , Animales , Acetilcolinesterasa/genética , Insecticidas/toxicidad , Compuestos Organofosforados/toxicidad , Encéfalo , DolorRESUMEN
Insect glutathione S-transferases (GSTs) participate in detoxifying insecticides and plant metabolites in two different ways, metabolizing toxic components and remedying oxidative stress. Here in Nilaparvata lugens, a major insect pest on rice, the roles of cytosolic GSTs in resistance to insecticides and to plant defences were evaluated. The over-expression in four resistant strains indicated that NlGSTs1 and NlGSTs2 were essential to resistances to four test insecticides and H2O2 through an antioxidation mechanism. RNAi verified the antioxidation function of NlGSTs1 and NlGSTs2 in the resistances as a common mechanism, regardless of the structural differences among insecticides and H2O2. NlGSTs1 and NlGSTs2 also provided protection for N. lugens against rice defense by the same mechanism, reducing H2O2 levels when N. lugens were fed on the resistant rice variety Mudogo. The antioxidation activity of recombinant NlGSTs1 and NlGSTs2 is higher than their direct detoxification, which supported the ability of these two GSTs to remedy oxidative stress. For oxidative stress remediation as a common mechanism of NlGSTs1 and NlGSTs2 in both insecticide resistance and host adaptability, the development of insecticide resistance might enhance the ability of insects to remedy oxidative stress from feeding on resistant rice variety and thus to lower the resistance level of rice variety to N. lugens. The results call for careful assessment on N. lugens control when both insecticides and resistant rice variety are applied.
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Insecticidas , Oryza , Resistencia a los Insecticidas/genética , Oryza/genética , Insecticidas/farmacología , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , AntioxidantesRESUMEN
As one of the most important detoxification enzymes in insects, Glutathione S-transferases (GSTs) play key roles in insecticide resistance via direct metabolism and protection against oxidative stress induced by insecticide exposure. Insect GSTs are often considered as the phase II detoxification enzymes, they have potential function to metabolize fipronil as well as its fipronil's metabolites. In the fipronil-resistant Nilaparvata lugens strain G28, GSTs' inhibitor DEM (diethyl maleate) showed the optimal synergistic effects (5.73-fold), indicating the essential roles of GSTs in the resistance to fipronil in this insect species. Four GST genes, NlGSTs1, NlGSTs2, NlGSTe1 and NlGSTd1, were found over-expressed in G28 when compared to its relative susceptible counterpart strain S28. The roles of these four GSTs in fipronil resistance were confirmed via RNAi. The four GST genes were highly over-expressed in the midgut and/or fat body with detoxification action, which might provide more chances for insects to metabolize fipronil and its metabolites. Additionally, the higher induction levels in the GST gene expression by insecticides in the midgut and/or fat body compared to the whole insect also supported the significant roles of the four GSTs in the detoxification. Above all, the results provided evidences to understand the functions of GSTs in fipronil resistance in N. lugens, and gave a reference for other insects in fipronil resistance.
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Hemípteros , Insecticidas , Animales , Glutatión Transferasa/genética , Hemípteros/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , PirazolesRESUMEN
Cortical microtubule (MT) arrays play a critical role in plant cell shape determination by defining the direction of cell expansion. As plants continuously adapt to ever-changing environmental conditions, multiple environmental and developmental inputs need to be translated into changes of the MT cytoskeleton. Here, we identify and functionally characterize an auxin-inducible and MT-localized protein OsIQ67-DOMAIN14 (OsIQD14), which is highly expressed in rice seed hull cells. We show that while deficiency of OsIQD14 results in short and wide seeds and increases overall yield, overexpression leads to narrow and long seeds, caused by changed MT alignment. We further show that OsIQD14-mediated MT reordering is regulated by specifically affecting MT dynamics, and ectopic expression of OsIQD14 in Arabidopsis could change the cell shape both in pavement cells and in hypocotyl cells. Additionally, OsIQD14 activity is tightly controlled by calmodulin proteins, providing an alternative way to modify the OsIQD14 activity. Our results indicate that OsIQD14 acts as a key factor in regulating MT rearrangements in rice hull cells and hence the grain shape, and allows effective local cell shape manipulation to improve the rice yield trait.
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Proteínas de Arabidopsis , Oryza , Citoesqueleto , Proteínas Asociadas a Microtúbulos , Microtúbulos , Oryza/genéticaRESUMEN
STUDY OBJECTIVE: This study aims to evaluate the efficacy of the combination of bipolar radiofrequency impedance-controlled endometrial ablation (NovaSure; Hologic Inc., Bedford, MA) and levonorgestrel intrauterine system (LNG-IUS; Mirena; Schering AG, Berlin, Germany) placement in comparison with NovaSure endometrial ablation alone in patients with abnormal uterine bleeding (AUB). DESIGN: A propensity score matching study. SETTING: Beijing Tiantan Hospital, Capital Medical University, Beijing, China. PATIENTS: A retrospective study was conducted on 246 patients with AUB who underwent NovaSure endometrial ablation with (NovaSure+LNG-IUS group) or without (NovaSure group) LNG-IUS between January 2013 and August 2016. To overcome selection bias, propensity score matching was used to establish a 1:1 match between these 2 groups. Accordingly, 41 patients were included in each group. INTERVENTION: NovaSure endometrial ablation, immediately followed by LNG-IUS insertion in the NovaSure+LNG-IUS group, and NovaSure endometrial ablation alone in the control group. MEASUREMENTS AND MAIN RESULTS: Follow-up assessments performed at postablation months 6, 12, and 24 revealed the following: The rate of amenorrhea (78.05% vs 46.34%, 85.37% vs 53.65%, and 87.80% vs 58.54%, respectively; p <.005) and the rate of dysmenorrhea remission (100% vs 70.59%, 100% vs 64.70%, and 100% vs 64.70% [p <.05, p <.01, and p <.01], respectively) were significantly higher in the NovaSure+LNG-IUS group than in the NovaSure group. The rate of reinterventions was similar for both groups at postablation month 6. However, at postablation months 12 and 24, these rates were significantly lower in the NovaSure+LNG-IUS group than in the NovaSure group (0 vs 14.63% and 2.44% vs 21.95% [p <.05 and p <.01], respectively). CONCLUSION: For women with AUB, the combination of NovaSure endometrial ablation and LNG-IUS is more effective than NovaSure alone in achieving amenorrhea, alleviating dysmenorrhea and reducing reinterventions.
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Técnicas de Ablación Endometrial/métodos , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Ablación por Radiofrecuencia/métodos , Hemorragia Uterina/cirugía , Adulto , China/epidemiología , Terapia Combinada , Investigación sobre la Eficacia Comparativa , Anticonceptivos Femeninos , Impedancia Eléctrica/uso terapéutico , Técnicas de Ablación Endometrial/efectos adversos , Técnicas de Ablación Endometrial/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Dispositivos Intrauterinos Medicados/efectos adversos , Dispositivos Intrauterinos Medicados/estadística & datos numéricos , Levonorgestrel/efectos adversos , Persona de Mediana Edad , Puntaje de Propensión , Ablación por Radiofrecuencia/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia Uterina/epidemiología , Adulto JovenRESUMEN
STUDY OBJECTIVE: To evaluate the feasibility, effectiveness, and reproductive outcome of hysteroscopic management using the Hysteroscopy Endo Operative system (HEOS) in patients with diffuse uterine leiomyomatosis (DUL). DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Beijing Tiantan Hospital, Capital Medical University, Beijing, China. PATIENTS: Eight women of reproductive age suffering from menorrhagia and anemia or infertility diagnosed with DUL by ultrasonography and hysteroscopy. INTERVENTIONS: Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS was performed to excise submucous myomas (including types 0, I, and II), leaving other intramural myomas in place. The fenestration method is used in electrical hysteroscopic myomectomy. Postoperative endometrial repair and synechiae, menstrual improvement, conception, and pregnancy were recorded. MEASUREMENTS AND MAIN RESULTS: Two patients underwent a single hysteroscopic myomectomy, whereas 6 patients underwent 2 to 3 myomectomies. No complications were observed. The mean follow-up period was 39.13 ± 17.01 months (range, 21-67). The endometrium recovered 2 to 3 months after the initial surgery, and 100% improvement in menstruation was observed. Two patients had mild synechia after the first hysteroscopic surgery. Seven patients conceived spontaneously (postoperative pregnancy rate, 87.5%), 6 of whom had a full-term pregnancy. One patient suffered a miscarriage in the second trimester (live birth rate, 75%). CONCLUSION: Hysteroscopic surgery using cold graspers combined with electric loop by the HEOS is a feasible and effective for treatment of DUL because it preserves the uterus and yields favorable reproductive outcomes. The cold surgery and fenestration method minimizes electrical and thermal damage to the endometrium surrounding the myoma, consequently reducing surgical risks.
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Histeroscopía/métodos , Leiomiomatosis/cirugía , Índice de Embarazo , Miomectomía Uterina/métodos , Neoplasias Uterinas/cirugía , Adulto , China/epidemiología , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Histeroscopía/efectos adversos , Histeroscopía/estadística & datos numéricos , Recién Nacido , Infertilidad/diagnóstico , Infertilidad/epidemiología , Infertilidad/cirugía , Leiomiomatosis/epidemiología , Nacimiento Vivo/epidemiología , Menorragia/complicaciones , Embarazo , Estudios Retrospectivos , Adherencias Tisulares/diagnóstico , Adherencias Tisulares/epidemiología , Adherencias Tisulares/cirugía , Resultado del Tratamiento , Neoplasias Uterinas/epidemiologíaRESUMEN
PURPOSES: To describe the fertility outcomes after hysteroscopic adhesiolysis combined with preoperative hormone treatment in women with intrauterine adhesion (IUA). METHODS: This study is a retrospective cohort study. A total of 230 patients with IUA underwent hysteroscopic adhesiolysis combined with hormone treatment from Jan 2012 to Jun 2018. 148 patients who received preoperative estrogen treatment were enrolled into group A and 82 patients without preoperative estrogen treatment were enrolled into group B. All the patients underwent hysteroscopic adhesiolysis and received postoperative estrogen therapy, intrauterine indwelling device. Second or third look was performed after 2-3 months. RESULTS: 90.87% (209/230) patients complete the study. The AFS scores at baseline were higher in the group A than group B. After the preoperative E2 treatment, group A achieved the comparable AFS score to group B before the surgery. The cumulative fertility rate in group A was comparable in group B, both in the ITT analysis (49.32% vs. 52.44%, p = 0.651) and the PP analysis (54.07% vs.58.10%, p = 0.575).The mean conception time was also similar in group A and group B (8.30 ± 6.47 vs. 8.54 ± 5.68 months, p = 0.837). Besides, the surgery times in group A were less than group B. There was no difference in the rate of adverse events between two groups. CONCLUSIONS: Hysteroscopic adhesiolysis combined with preoperative oestrogen could reduce the preoperative AFS scores and the times of surgery which yield a similar conception rate in women with less severe intrauterine adhesions.
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Estrógenos/uso terapéutico , Fertilidad/efectos de los fármacos , Histeroscopía/métodos , Adherencias Tisulares/tratamiento farmacológico , Enfermedades Uterinas/tratamiento farmacológico , Adulto , Estrógenos/farmacología , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades Uterinas/cirugíaRESUMEN
A new polyketide containing the benzoisoquinoline-9-one moiety, peyronetide A (1), and three other new derivatives peyronetides Bâ»D (2â»4), as well as one known compound (5) were purified from the cultured broth of the endophytic fungus Peyronellaea sp. FT431, which was isolated from the Hawaiian indigenous plant, Verbena sp. The structures of the new compounds were determined through the analysis of HRMS and NMR spectroscopic data. Compounds 1, 2, and 5 showed cytotoxic activities against TK-10 (human kidney adenocarcinoma cells), cisplatin sensitive A2780S (human ovarian carcinoma cells), and cisplatin resistant A2780CisR cell lines, with IC50 values between 6.7 to 29.2 µM.
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Ascomicetos/química , Proliferación Celular/efectos de los fármacos , Isoquinolinas/farmacología , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Cisplatino/efectos adversos , Resistencia a Antineoplásicos/efectos de los fármacos , Endófitos/química , Hawaii , Humanos , Concentración 50 Inhibidora , Isoquinolinas/química , Isoquinolinas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Three new ulapualides (3-5) were isolated from egg masses of the nudibranch Hexabranchus sanguineus. The structures of 3-5 were deduced by analyses of physical and spectroscopic data in comparisons with ulapualides A (1) and B (2). Ulapualide C demonstrated submicromolar cytotoxicity against select NCI cell lines (768-0, DU-145, MDA-MB-231, and A549) with the most potent activity against MDA-MB-231 cells (IC50 0.58 µM). Ulapualides A (1) and B (2) were 2- to 4-fold more potent than 3.
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Gastrópodos/química , Óvulo/química , Oxazoles/aislamiento & purificación , Animales , Ensayos de Selección de Medicamentos Antitumorales , Hawaii , Humanos , Biología Marina , Estructura Molecular , Oxazoles/química , Oxazoles/farmacologíaRESUMEN
Etofenprox, a non-ester pyrethroid insecticide, will be registered to control rice pests such as the brown planthopper (BPH, Nilaparvata lugens Stål) in mainland China. Insecticide resistance is always a problem to the effective control of N. lugens by chemical insecticides. An etofenprox resistance selection of N. lugens was performed in order to understand the related mechanisms. Through successive selection by etofenprox for 16 generations in the laboratory, an etofenprox-resistant strain (G16) with the resistance ratio (RR) of 422.3-fold was obtained. The resistance was partly synergised (2.68-fold) with the metabolic inhibitor PBO, suggesting a role for P450 monooxygenases. In this study, 11 P450 genes were significantly up-regulated in G16, among which eight genes was above 2.0-fold higher than that in US16, a population with the same origin of G16 but without contacting any insecticide in the laboratory. The expression level of four genes (CYP6AY1, CYP6FU1 and CYP408A1 from Clade 3, and CYP425A1 from Clade 4) were above 4.0-fold when compared to US16. RNA interference (RNAi) was performed to evaluate the importance of the selected P450s in etofenprox resistance. When CYP6FU1, CYP425A1 or CYP6AY1 was interfered, the susceptibility was significantly recovered in both G16 and US16, while the knockdown of CYP408A1 or CYP353D1 did not cause significant changes in etofenprox susceptibility. We supposed that CYP6FU1 was the most important P450 member for etofenprox resistance because of the highest expression level and the most noticeable effects on resistance ratios following RNAi.
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Sistema Enzimático del Citocromo P-450/genética , Hemípteros/efectos de los fármacos , Proteínas de Insectos/genética , Resistencia a los Insecticidas/genética , Insecticidas/toxicidad , Piretrinas/toxicidad , Animales , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hemípteros/enzimología , Hemípteros/genética , Organofosfatos/farmacología , Butóxido de Piperonilo/farmacología , Interferencia de ARN , ARN Mensajero/metabolismoRESUMEN
A new N-methoxypyridone analog (1), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11S-hydroxy-1-methoxyfusaricide (1) by extensive spectroscopic analysis and comparison with the literature. The absolute configuration of 1 was determined by comparison with the experimental and calculated ECD spectra. The absolute configuration of compound 3 was investigated and renamed as (+)-epipyridone by comparison of the optical rotation and CD spectrum with those of 1. The other known compounds were identified as epicoccarine B (2), D8646-2-6 (4), and iso-D8646-2-6 (5). Compounds 4 and 5 showed modest inhibitory activity towards pathogenic fungi. Epicoccarine B (2) inhibited A2780 and TK-10 with an IC50 value of 22 µM.
Asunto(s)
Ascomicetos/química , Benzopiranos/química , Endófitos/química , Piridonas/química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Benzopiranos/aislamiento & purificación , Benzopiranos/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Hawaii , Piridonas/aislamiento & purificación , Piridonas/farmacología , Pirrolidinonas/química , Pirrolidinonas/aislamiento & purificación , Pirrolidinonas/farmacologíaRESUMEN
Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlα8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlα8 was observed during selection. RNA interference knockdown of Nlα8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlα8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlα8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlα8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlα8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance.
Asunto(s)
Colinérgicos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Imidazoles/farmacología , Nitrocompuestos/farmacología , ARN Mensajero/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Animales , Resistencia a Medicamentos/efectos de los fármacos , Sinergismo Farmacológico , Insectos , Insecticidas/farmacología , Neonicotinoides , Interferencia de ARN/fisiología , ARN Bicatenario/farmacología , Ensayo de Unión Radioligante , Ratas , Tritio/farmacocinéticaRESUMEN
The brown planthopper, Nilaparvata lugens (Stål), is a destructive insect pest on rice throughout Asia. As a visible genetic marker, red eye mutant colony of brown planthopper is a valuable material. Here, we established the near-isogenic lines, NIL-BB and NIL-rr, through mating red eye females to brown eye brothers for eight successive generations. Biological experiments showed that NIL-BB had big fitness cost; however, NIL-rr had comparable survival and fertility parameters with BB, a normal laboratory brown planthopper strain. Significantly lower number eggs per female and egg hatchability were the key factors resulting in big fitness cost of NIL-BB. The population trend indexes of BB, NIL-rr, and NIL-BB were 52.18, 43.80, and 4.19, respectively. Real-time PCR study suggested that the poorer fertility of NIL-BB was not mediated by the differential expression of genes relating to oogenesis. The stronger fitness of NIL-rr compared with NIL-BB may be caused by the eye mutant gene or its closely linked genes having stronger compensation ability for reproduction. The comparable fitness of NIL-rr with BB indicated that NIL-rr may be used in field research. The NIL-BB strain with significantly declined fecundity and survival ability can be used as study model for the signal pathways relating to fecundity.