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BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.
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BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.
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Graph states are an important class of multipartite entangled states. Previous experimental generation of graph states and in particular the Greenberger-Horne-Zeilinger (GHZ) states in linear optics quantum information schemes is subjected to an exponential decay in efficiency versus the system size, which limits its large-scale applications in quantum networks. Here, we demonstrate an efficient scheme to prepare graph states with only a polynomial overhead using long-lived atomic quantum memories. We generate atom-photon entangled states in two atomic ensembles asynchronously, retrieve the stored atomic excitations only when both sides succeed, and further project them into a four-photon GHZ state. We measure the fidelity of this GHZ state and further demonstrate its applications in the violation of Bell-type inequalities and in quantum cryptography. Our work demonstrates the prospect of efficient generation of multipartite entangled states in large-scale distributed systems with applications in quantum information processing and metrology.
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The nanoflakes of SnS2/SnO2heterostructure and SnS2were synthesized by a one-step SnO2-templated chemical vapor deposition method. The metal oxide-assisted growth mechanism of SnS2/SnO2heterostructure and SnS2nanoflakes were realized through investigating serial microstructures of products with varied growth time. Furthermore, the photocatalytic activity for MB dyes degradation of varied growth time products was used to explore the effect of product microstructure under the visible light irradiation. The SnO2/SnS2heterostructure and the oxide vacancies of nanoflakes demonstrated an improved visible light photocatalytic performance for MB degradation, which was around twice of the pure SnS2nanoflakes and better than P25. The results of different scavengers on the degradation efficiency for MB indicate the·O2-, and ·OH are the main active species in the photodegradation reaction. The one-step growth mechanism of SnS2/SnO2could prove a facile process to grow metal oxide-metal sulfide heterostructure.
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Topological defects are discontinuities of a system protected by global properties, with wide applications in mathematics and physics. While previous experimental studies mostly focused on their classical properties, it has been predicted that topological defects can exhibit quantum superposition. Despite the fundamental interest and potential applications in understanding symmetry-breaking dynamics of quantum phase transitions, its experimental realization still remains a challenge. Here, we report the observation of quantum superposition of topological defects in a trapped-ion quantum simulator. By engineering long-range spin-spin interactions, we observe a spin kink splitting into a superposition of kinks at different positions, creating a "Schrodinger kink" that manifests nonlocality and quantum interference. Furthermore, by preparing superposition states of neighboring kinks with different phases, we observe the propagation of the wave packet in different directions, thus unambiguously verifying the quantum coherence in the superposition states. Our work provides useful tools for nonequilibrium dynamics in quantum Kibble-Zurek physics.
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Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.
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Infecções por Helicobacter , Helicobacter pylori , Células-Tronco Neoplásicas , Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas , Animais , Feminino , Humanos , Masculino , Camundongos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fosforilação , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genéticaRESUMO
Most of the smallest flying insects use bristled wings. It was observed that during the second half of their upstroke, the left and right wings become parallel and close to each other at the back, and move upward at zero angle of attack. In this period, the wings may produce drag (negative vertical force) and side forces which tend to push two wings apart. Here we study the aerodynamic forces and flows of two simplified bristled wings experiencing such a motion, compared with the case of membrane wings (flat-plate wings), to see if there is any advantage in using the bristled wings. The method of computational fluid dynamics is used in the study. The results are as follows. In the motion of two bristled wings, the drag acting on each wing is 40% smaller than the case of a single bristled wing conducting the same motion, and only a very small side force is produced. But in the case of the flat-plate wings, although there is similar drag reduction, the side force on each wing is larger than that of the bristled wing by an order of magnitude (the underlying physical reason is discussed in the paper). Thus, if the smallest insects use membrane wings, their flight muscles need to overcome large side forces in order to maintain the intended motion for less negative lift, whereas using bristled wings do not have this problem. Therefore, the adoption of bristled wings can be beneficial during upward movement of the wings near the end of the upstroke, which may be one reason why most of the smallest insects adopt them.
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Voo Animal , Asas de Animais , Animais , Fenômenos Biomecânicos , Voo Animal/fisiologia , Insetos/fisiologia , Modelos Biológicos , Asas de Animais/fisiologiaRESUMO
The authors report a clinically distinctive form of elevated intraocular pressure-induced interface keratopathy that occurred after a pars plana vitrectomy with intraocular gas tamponade for a macular hole in the right eye in a 35-year-old woman who had laser in situ keratomileusis in both eyes 8 years previously. The intraocular pressure was increased to 37 mm Hg after surgery. Diffuse lamellar keratitis-like interface infiltration was found with concurrent elevated intraocular pressure. The interface infiltration did not respond to steroids but resolved after the intraocular pressure was controlled. This case suggests that interface keratopathy is associated with increased intraocular pressure. Assessment of intraocular pressure is essential in patients presenting with interface keratopathy, especially in those who have undergone posterior segment operations with gas tamponade.
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Doenças da Córnea/etiologia , Gases/administração & dosagem , Gases/efeitos adversos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Hipertensão Ocular/complicações , Hipertensão Ocular/etiologia , Vitrectomia/métodos , Adulto , Anti-Hipertensivos/uso terapêutico , Doenças da Córnea/patologia , Feminino , Humanos , Injeções Intraoculares , Pressão Intraocular , Prontuários Médicos , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Perfurações Retinianas/cirurgia , Fatores de Tempo , Tonometria OcularRESUMO
Morning glory disk anomaly (MGDA) is a congenital malformation of the optic disk that is usually unilateral. It has characteristic fundus findings, including enlarged optic disk opening and funnel-shaped excavation of the peripapillary fundus. Optical coherence tomography (OCT) with micrometer resolution and cross-sectional imaging capabilities can provide detailed information about the structure of the living eye. Some reports have used OCT to demonstrate the structure of the disk in older patients with MGDA but, to our knowledge, no quantitative OCT report concerning a child with MGDA has been published previously.