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OBJECTIVE: To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma (SCNSL). METHODS: Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected. A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival. Multivariate logistic regression analysis was used to explore the adverse prognostic factors. RESULTS: Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research. Their 2-year overall survival (OS) rate was 46.01% and median survival time was 18.1 months. The 2-year OS rates of HD-MTX group and TMZ group were 34.3% and 61%, median survival time were 8.7 and 38.3 months, and median progression-free survival time were 8.1 and 47 months, respectively. Multivariate logistic regression analysis showed that age, sex, IPI, Ann Arbor stage were correlated with patient survival time. The median survival time of patients with CD79B, KMT2D, CXCR4, ERBB2, TBL1XR1, BTG2, MYC, MYD88, and PIM1 mutations was 8.2 months, which was lower than the overall level. CONCLUSION: HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.
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Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Humanos , Neoplasias del Sistema Nervioso Central/terapia , Estudios Retrospectivos , Pronóstico , Masculino , Femenino , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metotrexato , Resultado del Tratamiento , Persona de Mediana Edad , Estudios de CohortesRESUMEN
Cavitation may occur in water-jet pump during operation of water-jet propulsion vessel, and once cavitation occurs, the tip clearance pulsating pressure of the impeller may be intensified, resulting in increased vibration of the water-jet propulsion unit. In this paper, the cavitation pulsating pressure characteristics at different positions in the pump are studied by experiment and numerical simulation, and the pulsating pressure characteristics in tip clearance are mainly researched. Based on Star-CCM+ commercial software, unsteady Reynolds-averaged Navier-Stokes equations(RANS) numerical simulation is carried out, and the feasibility of the numerical simulation method is verified by uncertainty analysis. The results show that the cavitation pulsating pressure near the leading edge of the impeller in the tip clearance is the largest. The variation of the tip clearance pulsating pressure with the intensification of cavitation is studied by numerical simulation, and its mechanism is revealed. A dimensionless coefficient of net positive suction head (CNPSH) is proposed, and the study shows that the cavitation pulsation pressure coefficients of pumps of different scales are equal when the working conditions are similar and the CNPSH are equal, which indicates that the cavitation pulsating pressure performance of full scale pump can be predicted by model scale. It is of great significance to evaluate the vibration performance of the full scale water-jet propulsion.
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Presión , Agua , Simulación por Computador , Modelos Teóricos , VibraciónRESUMEN
Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.
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Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/diagnóstico por imagen , Neoplasias/genética , Nanopartículas/uso terapéutico , Nanopartículas/química , Nanotecnología/tendencias , Nanomedicina/tendencias , Sistemas de Liberación de MedicamentosRESUMEN
BACKGROUND: Straw incorporation serves as an effective strategy to enhance soil fertility and soil microbial biomass carbon (SMBC), which in turn improves maize yield and agricultural sustainability. However, our understanding of nitrogen (N) fertilization and straw incorporation into soil microenvironment is still evolving. This study explored the impact of six N fertilization rates (N0, N100, N150, N200, N250, and N300) with and without straw incorporation on soil fertility, SMBC, enzyme activities, and maize yield. RESULTS: Results showed that both straw management and N fertilization significantly affected soil organic carbon (SOC), total N, SMBC, soil enzyme activities, and maize yield. Specifically, the N250 treatment combined with straw incorporation significantly increased SOC, total N, and SMBC compared to lower fertilization rates. Additionally, enzyme activities such as urease, cellulase, sucrose, catalase, and acid phosphatase reached their peak during the V6 growth stage in the N200 treatment under for both straw management conditions. Compared to N250 and N300 treatments of traditional planting, the N200 treatment with residue incorporation significantly increased yield by 8.30 and 4.22%, respectively. All measured parameters, except for cellulase activity, were significantly higher in spring than in the autumn across both study years, with notable increases observed in 2021. CONCLUSIONS: These findings suggest that optimal levels of SOC, soil total N (STN), and SMBC, along with increased soil enzyme activities, is crucial for sustaining soil fertility and enhancing maize grain yield under straw incorporation and N200 treatments.
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Fertilizantes , Nitrógeno , Suelo , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Suelo/química , Nitrógeno/metabolismo , Producción de Cultivos/métodos , Carbono/metabolismo , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Biomasa , Microbiología del Suelo , Agricultura/métodosRESUMEN
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and presents a significant threat to human health. Despite its prevalence, the underlying regulatory mechanisms of HCC remain unclear. In this study, we integrated RNA-seq datasets, proteome dataset and survival analysis and unveiled Stratifin (SFN) as a potential prognostic biomarker for HCC. SFN knockdown inhibited HCC progression in cell cultures and mouse models. Conversely, ectopic expression of Sfn in primary mouse HCC model accelerated HCC progression. Mechanistically, SFN acted as an adaptor protein, activating AKT1 signaling by fostering the interaction between PDK1 and AKT1, with the R56 and R129 sites on SFN proving to be crucial for this binding. In the syngeneic implantation model, the R56A/R129A mutant of SFN inhibited Akt signaling activation and impeded HCC growth. Additionally, peptide inhibitors designed based on the binding motif of AKT1 to SFN significantly inhibited HCC progression. In summary, our findings establish that SFN promotes HCC progression by activating AKT signaling through the R56 and R129 binding sites. This discovery opens new avenues for a promising therapeutic strategy for the treatment of HCC.
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Chronic hepatitis B virus (HBV) infection affects 300 million patients worldwide1,2, in whom virus-specific CD8 T cells by still ill-defined mechanisms lose their function and cannot eliminate HBV-infected hepatocytes3-7. Here we demonstrate that a liver immune rheostat renders virus-specific CD8 T cells refractory to activation and leads to their loss of effector functions. In preclinical models of persistent infection with hepatotropic viruses such as HBV, dysfunctional virus-specific CXCR6+ CD8 T cells accumulated in the liver and, as a characteristic hallmark, showed enhanced transcriptional activity of cAMP-responsive element modulator (CREM) distinct from T cell exhaustion. In patients with chronic hepatitis B, circulating and intrahepatic HBV-specific CXCR6+ CD8 T cells with enhanced CREM expression and transcriptional activity were detected at a frequency of 12-22% of HBV-specific CD8 T cells. Knocking out the inhibitory CREM/ICER isoform in T cells, however, failed to rescue T cell immunity. This indicates that CREM activity was a consequence, rather than the cause, of loss in T cell function, further supported by the observation of enhanced phosphorylation of protein kinase A (PKA) which is upstream of CREM. Indeed, we found that enhanced cAMP-PKA-signalling from increased T cell adenylyl cyclase activity augmented CREM activity and curbed T cell activation and effector function in persistent hepatic infection. Mechanistically, CD8 T cells recognizing their antigen on hepatocytes established close and extensive contact with liver sinusoidal endothelial cells, thereby enhancing adenylyl cyclase-cAMP-PKA signalling in T cells. In these hepatic CD8 T cells, which recognize their antigen on hepatocytes, phosphorylation of key signalling kinases of the T cell receptor signalling pathway was impaired, which rendered them refractory to activation. Thus, close contact with liver sinusoidal endothelial cells curbs the activation and effector function of HBV-specific CD8 T cells that target hepatocytes expressing viral antigens by means of the adenylyl cyclase-cAMP-PKA axis in an immune rheostat-like fashion.
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Linfocitos T CD8-positivos , Hepatitis B Crónica , Hígado , Animales , Humanos , Masculino , Ratones , Linfocitos T CD8-positivos/enzimología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Modulador del Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Hepatocitos/inmunología , Hepatocitos/virología , Hígado/inmunología , Hígado/virología , Fosforilación , Transducción de Señal , Activación de LinfocitosRESUMEN
The rapid development of computer vision technologies and applications has brought forth a range of social and ethical challenges. Due to the unique characteristics of visual technology in terms of data modalities and application scenarios, computer vision poses specific ethical issues. However, the majority of existing literature either addresses artificial intelligence as a whole or pays particular attention to natural language processing, leaving a gap in specialized research on ethical issues and systematic solutions in the field of computer vision. This paper utilizes bibliometrics and text-mining techniques to quantitatively analyze papers from prominent academic conferences in computer vision over the past decade. It first reveals the developing trends and specific distribution of attention regarding trustworthy aspects in the computer vision field, as well as the inherent connections between ethical dimensions and different stages of visual model development. A life-cycle framework regarding trustworthy computer vision is then presented by making the relevant trustworthy issues, the operation pipeline of AI models, and viable technical solutions interconnected, providing researchers and policymakers with references and guidance for achieving trustworthy CV. Finally, it discusses particular motivations for conducting trustworthy practices and underscores the consistency and ambivalence among various trustworthy principles and technical attributes.
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Inteligencia Artificial , Humanos , Inteligencia Artificial/ética , Inteligencia Artificial/tendencias , Confianza , Procesamiento de Lenguaje Natural , Minería de Datos/ética , BibliometríaRESUMEN
Loss-of-function mutations in CREBBP, which encodes for a histone acetyltransferase, occur frequently in B-cell malignancies, highlighting CREBBP deficiency as an attractive therapeutic target. Using established isogenic cell models, we demonstrated that CREBBP-deficient cells are selectively vulnerable to AURKA inhibition. Mechanistically, we found that co-targeting CREBBP and AURKA suppressed MYC transcriptionally and post-translationally to induce replication stress and apoptosis. Inhibition of AURKA dramatically decreased MYC protein level in CREBBP-deficient cells, implying a dependency on AURKA to sustain MYC stability. Furthermore, in vivo studies showed that pharmacological inhibition of AURKA was efficacious in delaying tumor progression in CREBBP-deficient cells and was synergistic with CREBBP inhibitors in CREBBP-proficient cells. Our study sheds light on a novel synthetic lethal interaction between CREBBP and AURKA, indicating that targeting AURKA represents a potential therapeutic strategy for high-risk B-cell malignancies harboring CREBBP inactivating mutations.
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Aurora Quinasa A , Proteína de Unión a CREB , Proteínas Proto-Oncogénicas c-myc , Mutaciones Letales Sintéticas , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Aurora Quinasa A/antagonistas & inhibidores , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The cerebrovascular endothelial cells with distinct characteristics line cerebrovascular blood vessels and are the fundamental structure of the blood-brain barrier, which is important for the development and homeostatic maintenance of the central nervous system. Cre-LoxP system-based spatial gene manipulation in mice is critical for investigating the physiological functions of key factors or signaling pathways in cerebrovascular endothelial cells. However, there is a lack of Cre recombinase mouse lines that specifically target cerebrovascular endothelial cells. Here, using a publicly available single-cell RNAseq database, we screened the solute carrier organic anion transporter family member 1a4 (Slco1a4) as a candidate marker of cerebrovascular endothelial cells. Then, we generated an inducible Cre mouse line in which a CreERT2-T2A-tdTomato cassette was placed after the initiation codon ATG of the Slco1a4 locus. We found that tdTomato, which can indicate the endogenous Slco1a4 expression, was expressed in almost all cerebrovascular endothelial cells but not in any other non-endothelial cell types in the brain, including neurons, astrocytes, oligodendrocytes, pericytes, smooth muscle cells, and microglial cells, as well as in other organs. Consistently, when crossing the ROSA26LSL-EYFP Cre reporter mouse, EYFP also specifically labeled almost all cerebrovascular endothelial cells upon tamoxifen induction. Overall, we generated a new inducible Cre line that specifically targets cerebrovascular endothelial cells.
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Encéfalo , Células Endoteliales , Integrasas , Animales , Ratones , Células Endoteliales/metabolismo , Integrasas/metabolismo , Integrasas/genética , Encéfalo/metabolismo , Técnicas de Sustitución del Gen , Ratones Transgénicos , Barrera Hematoencefálica/metabolismo , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Tamoxifeno/farmacología , Proteína Fluorescente RojaRESUMEN
Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.
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Espermatozoides , Humanos , Masculino , Espermatozoides/metabolismo , Síndrome , Teratozoospermia/genéticaRESUMEN
Henoch-Schönlein purpura (HSP) and pediatric-onset systemic lupus erythematosus (pSLE) are closely associated with vasculitis and vascular diseases. This study aimed to investigate the clinical diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE. We surveyed 82 HSP patients, 34 pSLE patients, and 10 healthy children. The expression levels of Ang-1, Ang-2, and Tie2 in the serum and urine were assessed using enzyme-linked immunosorbent assay. The diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE were evaluated using receiver operating characteristic curve analysis. The results revealed that the serum and urine expression levels of Ang-2 and Tie2 were significantly elevated in HSP and pSLE patients, whereas the Ang-1/Ang-2 values were reduced. Additionally, Ang-1 was highly expressed in the serum and urine of HSP patients and in the serum of pSLE patients. Ang-1, Ang-2, and Tie2 showed differential expression in various types of HSP and pSLE compared with their expression in healthy controls. In summary, Ang-1, Ang-2, and Tie2 can serve as biomarkers for HSP and pSLE. Moreover, Ang-1/Ang-2 values are reduced in HSP and pSLE patients. Ang-1, Ang-2, and Tie2 can be used as biomarkers for HSP and pSLE.
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BACKGROUND: Clinical nurses play an important role in ensuring patient safety. Nurses' work experience, organizational environment, psychological cognition, and behavior can all lead to patient safety issues. Improving nurses' attention to patient safety issues and enhancing their competence in dealing with complex medical safety issues can help avoid preventable nursing adverse events. Therefore, it is necessary to actively identify the latent profiles of patient safety competency of clinical nurses and to explore the influencing factors. METHODS: A cross-sectional design was conducted. A total of 782 Chinese registered nurses were included in the study. Demographic characteristics questionnaire, Error Management Climate scale, Security Questionnaire, Proactive Behavior Performance scale and Patient Safety Competency Self-Rating Scale of Nurses were used. Latent profile analysis (LPA) was performed to categorize nurses into latent subgroups with patient safety competency differences. Multinomial logistic regression was conducted to explore the influencing factors of nurses' patient safety competency (PSC) in different latent profiles. RESULTS: A total of 782 questionnaires were valid. Nurses' PSC was positively related to error management climate, and psychological safety and proactive behavior. The PSC score was 121.31 (SD = 19.51), showing that the PSC of clinical nurses was at the level of the medium on the high side. The error management climate score was 70.28 (SD = 11.93), which was at a relatively high level. The psychological safety score was 61.21 (SD = 13.44), indicating a moderate to low level. The proactive behavior score was 37.60 (SD = 7.33), which was at a high level. The latent profile analysis result showed that three groups of profile models were fitted acceding to the evaluation of PSC. They were defined as Low-competency Group (74 (9.5%)), Medium-competency Group (378 (48.3%)) and High-competency Group (330 (42.2%). Working years, professional titles, departments, error management climate, psychological security and proactive behavior were the influencing factors of PSC in three latent profiles. CONCLUSIONS: The PSC of clinical nurses had obvious classification characteristics, and the main influencing factors were working years, professional titles, working departments, error management climate, psychological security and proactive behavior. This study suggests that managers should pay attention to the continuous cultivation of patient safety competence among clinical nurses, provide targeted intervention measures for nurses at different work stages, professional titles, and departments, and use efficient management strategies to create a positive error management atmosphere. In patient safety management, providing nurses with more psychological security is conducive to stimulating more proactive behaviors and continuously improving the level of patient safety competence.
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Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer-1, 10 µM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2 ) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real-time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer-1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis-related proteins and skin barrier-related proteins, and increased levels of γ-H2AX and iron, whereas Fer-1 significantly increased their protein levels, and reduced levels of γ-H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer-1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer-1 significantly ameliorates UVB-induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R.
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Ferroptosis , Células HaCaT , Humanos , Especies Reactivas de Oxígeno/metabolismo , Proteómica , Apoptosis , Queratinocitos/metabolismo , Hierro , Rayos Ultravioleta/efectos adversosRESUMEN
Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or Pdgfrb+Kitl-, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.
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Hueso Esponjoso , Células Madre Mesenquimatosas , Células Madre , Huesos , Diferenciación Celular , Osteoblastos , Osteogénesis/genéticaRESUMEN
Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.
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Teleost fish type I IFNs and the associated receptors from the cytokine receptor family B (CRFB) are characterized by remarkable diversity and complexity. How the fish type I IFNs bind to their receptors is still not fully understood. In this study, we demonstrate that CRFB1 and CRFB5 constitute the receptor pair through which type I subgroup d IFN (IFNd) from large yellow croaker, Larimichthys crocea, activates the conserved JAK-STAT signaling pathway as a part of the antiviral response. Our data suggest that L. crocea IFNd (LcIFNd) has a higher binding affinity with L. crocea CRFB5 (LcCRFB5) than with LcCRFB1. Furthermore, we report the crystal structure of LcIFNd at a 1.49-Å resolution and construct structural models of LcIFNd in binary complexes with predicted structures of extracellular regions of LcCRFB1 and LcCRFB5, respectively. Despite striking similarities in overall architectures of LcIFNd and its ortholog human IFN-ω, the receptor binding patterns between LcIFNd and its receptors show that teleost and mammalian type I IFNs may have differentially selected helices that bind to their homologous receptors. Correspondingly, key residues mediating binding of LcIFNd to LcCRFB1 and LcCRFB5 are largely distinct from the receptor-interacting residues in other fish and mammalian type I IFNs. Our findings reveal a ligand/receptor complex binding mechanism of IFNd in teleost fish, thus providing new insights into the function and evolution of type I IFNs.
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Interferón Tipo I , Perciformes , Animales , Humanos , Filogenia , Peces/metabolismo , Interferón Tipo I/metabolismo , Proteínas de Peces/genética , Mamíferos/metabolismoRESUMEN
Background: Mucous membrane pemphigoid (MMP), a rare autoimmune vesiculous and erosive disorder, may affect multiple mucous membranes, with the oral cavity being the most commonly affected site. Its treatment depends on the site(s) of mucosal involvement and disease severity. Patients and Methods: A 62-year-old female patient with MMP that predominantly involved the oral cavity strongly rejected systemic corticosteroid or immunosuppressive agents and was successfully treated with abrocitinib, a highly selective JAK-1 inhibitor with a good safety profile. Results: The case demonstrated good efficacy and safety profile of abrocitinib for the treatment of MMP with predominant oral involvement. Conclusion: Abrocitinib is a promising agent for the treatment of MMP with oral involvement.
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OBJECTIVE: To examine the effects of the temporal inverted internal limiting membrane (ILM) flap technique for foveal reconstruction in patients with highly myopic macular hole-associated retinal detachment (MHRD). METHODS: A retrospective case series analysis of four patients (four eyes) with MHRD was conducted. The foveal optical coherence tomography changes following treatment using the temporal inverted ILM flap technique were evaluated. RESULTS: In Patient 1, the ILM bridged the macular hole and residual subretinal fluid on postoperative day 6, and complete retinal reattachment was achieved at 19 months. Patient 2 exhibited reduced retinal detachment, with visible ILM inversion and macular hole closure after 14 days. In Patient 3, macular hole closure and fovea formation had occurred by day 25, and the ILM flap was visible. At 2 months, the outer collagenous layer connection in the central fovea and recovery of the external limiting membrane and ellipsoid zone were observed. Patient 4 had a "white hole" MHRD, with macular hole closure achieved on postoperative day 20, albeit with a suboptimal foveal shape. CONCLUSION: The temporal inverted ILM flap technique in conjunction with vitrectomy facilitates foveal reconstruction in patients with successful treatment of MHRD, and this reconstruction process can be observed by optical coherence tomography.