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Chemoresistance remains a major challenge in the current treatment of acute myeloid leukemia (AML). The bone marrow microenvironment (BMM) plays a complex role in protecting leukemia cells from chemotherapeutics, and the mechanisms involved are not fully understood. Antileukemia drugs kill AML cells directly but also damage the BMM. Here, we determined antileukemia drugs induce DNA damage in bone marrow stromal cells (BMSCs), resulting in resistance of AML cell lines to adriamycin and idarubicin killing. Damaged BMSCs induced an inflammatory microenvironment through NF-κB; suppressing NF-κB with small molecule inhibitor Bay11-7082 attenuated the prosurvival effects of BMSCs on AML cell lines. Furthermore, we used an ex vivo functional screen of 507 chemokines and cytokines to identify 44 proteins secreted from damaged BMSCs. Fibroblast growth factor-10 (FGF10) was most strongly associated with chemoresistance in AML cell lines. Additionally, expression of FGF10 and its receptors, FGFR1 and FGFR2, was increased in AML patients after chemotherapy. FGFR1 and FGFR2 were also widely expressed by AML cell lines. FGF10-induced FGFR2 activation in AML cell lines operates by increasing P38 MAPK, AKT, ERK1/2, and STAT3 phosphorylation. FGFR2 inhibition with small molecules or gene silencing of FGFR2 inhibited proliferation and reverses drug resistance of AML cells by inhibiting P38 MAPK, AKT, and ERK1/2 signaling pathways. Finally, release of FGF10 was mediated by ß-catenin signaling in damaged BMSCs. Our data indicate FGF10-FGFR2 signaling acts as an effector of damaged BMSC-mediated chemoresistance in AML cells, and FGFR2 inhibition can reverse stromal protection and AML cell chemoresistance in the BMM.
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Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Humanos , Células da Medula Óssea/metabolismo , Dano ao DNA , Fator 10 de Crescimento de Fibroblastos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Células Estromais/metabolismo , Microambiente Tumoral , Comunicação ParácrinaRESUMO
The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [18F]AlF-ABI, a novel 18F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [18F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (KD = 35.6 nM). Upon administration, [18F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [18F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.
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Benzimidazóis , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Microambiente Tumoral , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Benzimidazóis/química , Benzimidazóis/farmacologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , HumanosRESUMO
Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.
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The properties of layered intercalation hybrids are closely related to interlayer molecular packing. To develop functional intercalation hybrids, it is essential to gain deep insights into interlayer molecular packing. This work reports a new comprehensive insight into the controllable multiphase interlayer molecular packing in 4-(phenylazo)benzoate anion-intercalated layered zinc hydroxide (LZH-4-PAB intercalation hybrids). The new insight breaks up the general understanding that the interlayer molecular packing of anions is usually single-phase, lacking diversity and controllability. Furthermore, it uncovers an interesting stepwise rather than the generally expected continuous phase transition of the interlayer molecular packing. The intercalated 4-PAB anions initially organize into the horizontal monolayer packing (θ = 0°, Phase I), which stepwise transforms to the tilted interdigitated antiparallel bilayer packing (θ ≈ 50°, Phase II) along with an increased intercalation loading and eventually to the vertical interdigitated antiparallel bilayer packing (θ = 90°, Phase III). The LZH-4-PAB hybrids exhibited a greatly enhanced interlayer molecular packing-dependent UV-vis absorption. This study provides helpful guidance for developing property-tailored intercalation hybrids. It may attract new interest in more layered intercalation hybrids. New and rich intercalation chemistry might be discovered in more functional intercalation hybrids beyond the 4-PAB anion-intercalated layered zinc hydroxide.
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Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98â¯000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.
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Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.
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Compostos Heterocíclicos de 4 ou mais Anéis , Lactonas , Oligoquetos , Poluentes do Solo , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Ecossistema , Simulação de Acoplamento Molecular , Glutationa Transferase/metabolismo , Poluentes do Solo/metabolismo , Superóxido Dismutase/metabolismo , Solo/química , Malondialdeído/metabolismo , Estresse OxidativoRESUMO
The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Glicólise , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Fatores de Transcrição Forkhead/metabolismoRESUMO
A nanozyme with neighboring single-iron sites (Fe2 -SAzyme) was introduced as a bioinspired catalase mimic, featuring excellent activity under varied conditions, twice as high as that of random Fe1 -SAzyme and ultrahigh H2 O2 affinity as that of bioenzymes. Surprisingly, the interatomic spacing tuning between adjacent iron sites also suppressed the competitive peroxidase pathway, remarkably increasing the catalase/peroxidase selectivity up to ~6 times compared to Fe1 -SAzyme. This dramatically switched the catalytic activity of Fe-SAzymes from generating (i.e. Fe1 -SAzymes, preferably mimicking peroxidase) to scavenging ROS (i.e. Fe2 -SAzymes, dominantly mimicking catalase). Theoretical and experimental investigations suggested that the pairwise single-iron sites may serve as a robust molecular tweezer to efficiently trap and decompose H2 O2 into O2 , via cooperative hydrogen-bonding induced end-bridge adsorption. The versatile mechano-assisted in situ MOF capsulation strategy enabled facile access to neighboring M2 -SAzyme (M=Fe, Ir, Pt), even up to a 1000â grams scale, but with no obvious scale-up effect for both structures and performances.
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Peroxidase , Peroxidases , Catalase , Adsorção , Corantes , Ferro , CatáliseRESUMO
OBJECTIVES: Long intergenic nonprotein coding RNA 1857 (LINC01857) has been identified to play an oncogenic role in different cancers. Nevertheless, its expression and biological role in endometrial carcinoma (EC) are not clear. DESIGN: This study was a basic research on cell biology. MATERIALS, SETTING, METHODS: EC cell lines were used in this study. RNA expressions in EC cells were examined through RT-qPCR. The impacts of LINC01857 silence on EC cell proliferation, apoptosis, migration, and invasion were evaluated through functional assays, and the underlying regulatory mechanism at a molecular level was analyzed via mechanism assays. RESULTS: LINC01857 expression was aberrantly high in EC cells. LINC01857 silence inhibited EC cell proliferation, migration, and invasion and promoted EC cell apoptosis. Mechanically, LINC01857 acted as a sponge of miR-19b-3p. Upregulation of miR-19b-3p hampered EC cell malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) was the target gene of miR-19b-3p, and MYCN depletion repressed the malignant behaviors of EC cells. Further, LINC01857 was verified to recruit ELAV-like RNA-binding protein 1 (ELAVL1) to stabilize MYCN mRNA. LIMITATIONS: The function of LINC01857 in EC remains to be further investigated with clinical samples and more cell lines involved. CONCLUSIONS: LINC01857 exacerbated EC cell malignant behaviors via the miR-19b-3p/ELAVL1/MYCN axis.
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Neoplasias do Endométrio , MicroRNAs , Feminino , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Semelhante a ELAV 1/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , RNA Longo não Codificante/genéticaRESUMO
In the present work, three kinds of nanosized SnO2 samples were successfully synthesized via a hydrothermal method with subsequent calcination at temperatures of 500 °C, 600 °C, and 700 °C. The morphology and structure of the as-prepared samples were characterized using X-ray diffraction, transmission electron microscopy, selected area electron diffraction, Brunauer-Emmett-Teller analysis, and X-ray photoelectron spectroscopy. The results clearly indicated that the SnO2 sample calcined at 600 °C had a higher amount of chemisorbed oxygen than the SnO2 samples calcined at 500 °C and 700 °C. Gas sensing investigations revealed that the cataluminescence (CTL) sensors based on the three SnO2 samples all exhibited high selectivity toward H2S, but the sensor based on SnO2-600 °C exhibited the highest response under the same conditions. At an operating temperature of 210 °C, the SnO2-600 °C sensor showed a good linear response to H2S in the concentration range of 20-420 ppm, with a detection limit of 8 ppm. The response and recovery times were 3.5 s/1.5 s for H2S gas within the linear range. The study on the sensing mechanism indicated that H2S was oxidized into excited states of SO2 by chemisorbed oxygen on the SnO2 surface, which was mainly responsible for CTL emission. The chemisorbed oxygen played an important role in the oxidation of H2S, and, as such, the reason for the SnO2-600 °C sensor showing the highest response could be ascribed to the highest amount of chemisorbed oxygen on its surface. The proposed SnO2-based gas sensor has great potential for the rapid monitoring of H2S.
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BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy with a prognosis that varies with genetic heterogeneity of hematopoietic stem/progenitor cells (HSPCs). Induction chemotherapy with cytarabine and anthracycline has been the standard care for newly diagnosed AML, but about 30% of patients have no response to this regimen. The resistance mechanisms require deeper understanding. METHODS: In our study, using single-cell RNA sequencing, we analyzed the heterogeneity of bone marrow CD34+ cells from newly diagnosed patients with AML who were then divided into sensitive and resistant groups according to their responses to induction chemotherapy with cytarabine and anthracycline. We verified our findings by TCGA database, GEO datasets, and multiparameter flow cytometry. RESULTS: We established a landscape for AML CD34+ cells and identified HSPC types based on the lineage signature genes. Interestingly, we found a cell population with CRIP1high LGALS1high S100Ashigh showing features of granulocyte-monocyte progenitors was associated with poor prognosis of AML. And two cell populations marked by CD34+ CD52+ or CD34+ CD74+ DAP12+ were related to good response to induction therapy, showing characteristics of hematopoietic stem cells. CONCLUSION: Our study indicates the subclones of CD34+ cells confers for outcomes of AML and provides biomarkers to predict the response of patients with AML to induction chemotherapy.
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Quimioterapia de Indução , Leucemia Mieloide Aguda , Humanos , Medula Óssea/patologia , Leucemia Mieloide Aguda/terapia , Antígenos CD34/uso terapêutico , Citarabina/uso terapêutico , Antraciclinas/uso terapêuticoRESUMO
Despite federal guidelines, many adolescents and emerging adults are not offered HIV testing by their healthcare providers. As such, many-including those who may be at high-risk for contracting HIV given their sexual and/or substance use risk-are not routinely tested. The current study examines sexual risk and substance use among emergency department patients aged 13-24 years (n = 147), who completed an automated screening as part of a tablet-based intervention designed to increase HIV testing. Twenty seven percent (n = 39) of participants chose to test for HIV after completing the tablet-based intervention. Among this sample, sexual risk was a significant independent predictor of HIV testing (χ2 = 16.50, p < 0.001). Problem substance use (e.g. trying but failing to quit) also predicted testing (χ2 = 7.43, p < 0.01). When considering these behaviors together, analyses indicated that the effect of problem substance use (ß = 0.648, p = 0.154) on testing is explained by sexual risk behavior (ß = 1.425, p < 0.01). The study's findings underscore the value of using routine automated risk screenings to collect sensitive data from emergency department patients, followed by computer-based HIV test offers for adolescent youth. Our research indicates tablet-based interventions can facilitate more accurate reporting of sexual behavior and substance use, and can also potentially increase HIV test uptake among those at risk.
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Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Serviço Hospitalar de Emergência , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Teste de HIV , Humanos , Assunção de Riscos , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Source tracing of heavy metals in agricultural soils is of critical importance for effective pollution control and targeting policies. It is a great challenge to identify and apportion the complex sources of soil heavy metal pollution. In this study, a traditional analysis method, positive matrix fraction (PMF), and three machine learning methodologies, including self-organizing map (SOM), conditional inference tree (CIT) and random forest (RF), were used to identify and apportion the sources of heavy metals in agricultural soils from Lianzhou, Guangdong Province, China. Based on PMF, the contribution of the total loadings of heavy metals in soil were 19.3% for atmospheric deposition, 65.5% for anthropogenic and geogenic sources, and 15.2% for soil parent materials. Based on SOM model, As, Cd, Hg, Pb and Zn were attributed to mining and geogenic sources; Cr, Cu and Ni were derived from geogenic sources. Based on CIT results, the influence of altitude on soil Cr, Cu, Hg, Ni and Zn, as well as soil pH on Cd indicated their primary origin from natural processes. Whereas As and Pb were related to agricultural practices and traffic emissions, respectively. RF model further quantified the importance of variables and identified potential control factors (altitude, soil pH, soil organic carbon) in heavy metal accumulation in soil. This study provides an integrated approach for heavy metals source apportionment with a clear potential for future application in other similar regions, as well as to provide the theoretical basis for undertaking management and assessment of soil heavy metal pollution.
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Mercúrio , Metais Pesados , Poluentes do Solo , Cádmio , Carbono , China , Monitoramento Ambiental/métodos , Chumbo , Aprendizado de Máquina , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análiseRESUMO
Temperature strongly modulates muscle development and growth in ectothermic teleosts; however, the underlying mechanisms remain largely unknown. In this study, primary cultures of skeletal muscle cells of Lateolabrax maculatus were conducted and reared at different temperatures (21, 25, and 28 °C) in both the proliferation and differentiation stages. CCK-8, EdU, wound scratch and nuclear fusion index assays revealed that the proliferation, myogenic differentiation, and migration processes of skeletal muscle cells were significantly accelerated as the temperature raises. Based on the GO, GSEA, and WGCNA, higher temperature (28 °C) induced genes involved in HSF1 activation, DNA replication, and ECM organization processes at the proliferation stage, as well as HSF1 activation, calcium activity regulation, myogenic differentiation, and myoblast fusion, and sarcomere assembly processes at the differentiation stage. In contrast, lower temperature (21 °C) increased the expression levels of genes associated with DNA damage, DNA repair and apoptosis processes at the proliferation stage, and cytokine signaling and neutrophil degranulation processes at the differentiation stage. Additionally, we screened several hub genes regulating myogenesis processes. Our results could facilitate the understanding of the regulatory mechanism of temperature on fish skeletal muscle growth and further contribute to utilizing rational management strategies and promoting organism growth and development.
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Fibras Musculares Esqueléticas , Músculo Esquelético , Animais , Diferenciação Celular/genética , Proliferação de Células/fisiologia , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , TemperaturaRESUMO
How to choose environmental policy instruments within a clearly defined scope of the market mechanism and government intervention will profoundly affect the policy effectiveness. Through a systematic review of 111 representative literature, this paper traces the theoretical development of environmental policy instruments, empirical analyses based on the CGE (Computable General Equilibrium) model, and globally practical experience. We find that the reflections on environmental policy instruments have shifted from command-based to market-based, from trade-offs between quantity-based and price-based instruments within the scope of market-based instruments to combining both, and finally a reasonable allocation of both command-based and market-based instruments. The CGE model promotes the shift, deepens the theory, and accelerates the transformation from theoretical thinking to practical application. By providing approaches to recognize and measure the overall economic costs of environmental policies, the CGE model plays an important role in validating efficiency theories, identifying efficiency losses, and amending policy instruments. It also promotes the implementation of environmental tools through region-pertinent settings and simulations. Based on reflections and discussions upon existing literature, we propose that the market should play a dominant role in allocating resources to obtain long-term environmental goals with corresponding environmental regulations as supplementary; under the circumstances with market efficiency losses, command-based instruments should be employed to cope with market failures. The results in this paper can facilitate the expansion of the environmental policy theory and also assist governments with better selection and formulation of environmental policy instruments relying on a solid theoretical basis and rational practical approaches.
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Política Ambiental , Políticas , China , EficiênciaRESUMO
Microtubules are dynamic cytoskeleton structures playing fundamental roles in plant responses to salt stress. The precise mechanisms by which microtubule organization is regulated under salt stress are largely unknown. Here, we report that Arabidopsis thaliana MICROTUBULE-DESTABILIZING PROTEIN 25 (MDP25; also known as PLASMA MEMBRANE-ASSOCIATED CATION-BINDING PROTEIN 1 (PCaP1)) helps regulate microtubule organization. Under salt treatment, elevated cytosolic Ca2+ concentration caused MDP25 to partially dissociate from the plasma membrane, promoting microtubule depolymerization. When Ca2+ signaling was blocked by BAPTA-AM or LaCl3 , microtubule depolymerization in wild-type and MDP25-overexpressing cells was slower, while there was no obvious change in mdp25 cells. Knockout of MDP25 improved microtubule reassembly and was conducive to microtubule integrity under long-term salt treatment and microtubule recovery after salt stress. Moreover, mdp25 seedlings exhibited a higher survival rate under salt stress. The presence microtubule-disrupting reagent oryzalin or microtubule-stabilizing reagent paclitaxel differentially affected the survival rates of different genotypes under salt stress. MDP25 promoted microtubule instability by affecting the catastrophe and rescue frequencies, shrinkage rate and time in pause phase at the microtubule plus-end and the depolymerization rate at the microtubule minus-end. These findings reveal a role for MDP25 in regulating microtubule organization under salt treatment by affecting microtubule dynamics.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Citosol/metabolismo , Microtúbulos/metabolismo , Estresse Salino , Plântula/metabolismoRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) exert an essential regulatory role in cancer progression. This work focuses on the role of LINC00958 in endometrial cancer (EC). METHODS: LINC00958 expression in EC tissues was examined by GEPIA database and TCGA-UCEC dataset. LINC00958, miR-145-3p, and TCF4 mRNA expression levels in EC tissues and cells were examined by qRT-PCR. Western blot was employed to determine TCF4, E-cadherin, and N-cadherin protein expression levels. After LINC00958 was overexpressed or silenced, cell proliferation was determined using Cell Counting Kit 8 (CCK-8) and bromodeoxyuridine (BrdU) incorporation experiments. Cell migration and invasion were examined by Transwell experiment. Dual-luciferase reporter gene or RNA immunoprecipitation (RIP) experiments were executed to validate the targeting relationships among LINC00958 and miR-145-3p and TCF4. The effects of LINC00958 on EC cell proliferation and metastasis were investigated in vivo using a nude mouse subcutaneous graft model and a caudal vein injection model. RESULTS: LINC00958 was remarkably upmodulated in EC. Moreover, its overexpression was strongly linked to unfavorable overall survival of the patients. Functional experiments confirmed that in vitro knockdown of LINC00958 suppressed EC cell proliferation and metastasis. LINC00958 was validated to decoy miR-145-3p and repressed its expression, and TCF4 was uncovered to be a target gene of miR-145-3p and negatively modulated by miR-145-3p. Furthermore, the function of LINC00958 was dependent on its regulation of miR-145-3p and TCF4. CONCLUSIONS: LINC00958 acts as an oncogenic lncRNA to regulate EC progression by modulating the miR-145-3p/TCF4 axis. Knockdown of LINC00958 impedes tumor growth and metastasis in vitro and in vivo, opening a new avenue for therapeutic intervention.
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Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição 4/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) has been identified in ovarian cancer. However, the expression and biological functions of LINC00852 in ovarian cancer are not understood. METHODS: The expressions of LINC00852, miR-140-3p and AGTR1 mRNA in ovarian cancer tissues and cells were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Gain- and loss-of-function assays were performed to explore the biological functions of LINC00852 and miR-140-3p in the progression of ovarian cancer in vitro. The bindings between LINC00852 and miR-140-3p were confirmed by luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. RESULTS: We found that LINC00852 expression was significantly up-regulated in ovarian cancer tissues and cells, whereas miR-140-3p expression was significantly down-regulated in ovarian cancer tissues. Functionally, LINC00852 knockdown inhibited the viability, proliferation and invasion of ovarian cancer cells, and promoted the apoptosis of ovarian cancer cells. Further investigation showed that LINC00852 interacted with miR-140-3p, and miR-140-3p overexpression suppressed the viability, proliferation and invasion of ovarian cancer cells. In addition, miR-140-3p interacted with AGTR1 and negatively regulated its level in ovarian cancer cells. Mechanistically, we found that LINC00852 acted as a ceRNA of miR-140-3p to promote AGTR1 expression and activate MEK/ERK/STAT3 pathway. Finally, LINC00852 knockdown inhibited the growth and invasion ovarian cancer in vivo. CONCLUSION: LINC00852/miR-140-3p/AGTR1 is an important pathway to promote the proliferation and invasion of ovarian cancer.
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Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Receptor Tipo 1 de Angiotensina/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The purpose of this study was to establish a novel rat model for ligamentum flavum (LF) hypertrophy using increased motion of lumbar and to elucidate the etiology of (LFH). METHODS: A total number of 30 male rats were used. The increased motion of lumbar was induced by surgical resection of L5/6 posterior elements (n = 15). The other rats underwent a sham operation (n = 15). After 8 weeks, all rats were taken lateral plain X-rays. The LF from L5/6 in both groups were harvested to investigate histological, immunohistological, and real-time PCR analysis. RESULTS: According to radiological results, the disc height ratio, flexion ratio, and extension ratio were larger in the rats in the experimental group than that of in the sham group. The HE staining showed that the LF thickness in the experimental group significantly increased in comparison to the sham group. The Masson trichrome staining showed that the ratio of elastic fibers to collagen fibers in experimental group was lower than that in the sham group. The protein and gene expression of TGF-ß1, TNF-α, IL-1ß, and Col 1 were significantly higher in the experimental group than that in the sham group. CONCLUSION: A relatively safe, simple, and rapid rat model of LFH using increased motion of lumbar was established. The increased motion of lumbar could lead to high expression of inflammatory and fibrotic factors in LF, causing the accumulation of collagen fibers and decreasing of elastic fibers.