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BACKGROUND AND OBJECTIVES: Diagnostic blood loss is a significant factor in the development of anaemia in neonates with very low birth weight. This study aimed to assess the clinical efficacy of intervention approaches involving varying diagnostic blood loss and red blood cell transfusion volumes in neonates with very low birth weights experiencing anaemia during hospitalization. MATERIALS AND METHODS: A total of 785 newborns with anaemia weighing less than 1500 g were enrolled from 32 hospitals in China. The study involved monitoring diagnostic blood loss and red blood cell transfusion and evaluating relevant interventions such as red blood cell transfusion and clinical outcomes. Three intervention approaches were established based on the difference between blood loss and transfusion (Intervention Approaches 0, 1 and 2). The primary outcomes measured were unsatisfactory weight gain during hospitalization and neonatal mortality. The secondary outcomes included related complications. RESULTS: In the non-hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.081-8.431, p = 0.035). Multivariate analysis revealed that Intervention Approach 1 had a protective effect on weight gain. In the hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (OR: 3.335, 95% CI: 1.785-6.234, p = 0.000) and mortality (OR: 5.341, 95% CI: 2.449-11.645, p = 0.000), while Intervention Approach 1 had the lowest incidence of intraventricular haemorrhage. Intervention Approach 1 demonstrated favourable outcomes in both anaemia groups. CONCLUSION: Intervention Approach 1 improved weight gain and reduced mortality and complications in both the non-hospital-acquired and hospital-acquired anaemia groups.
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Transfusión de Eritrocitos , Recién Nacido de muy Bajo Peso , Humanos , Recién Nacido , Femenino , Masculino , Estudios Retrospectivos , Hospitalización , Anemia/terapia , Anemia Neonatal/terapia , Anemia Neonatal/sangre , China/epidemiologíaRESUMEN
Organic-inorganic hybrid perovskites (OIHPs) have received particular attention due to their characteristic structural tunability and flexibility. These features make OIHPs behave with excellent modifications on macroscopic properties, such as ferroicity or semiconductor performances, etc. Herein, we report two 2D hybrid stibium-based halide perovskite (C3H7N)3Sb2X9 (X = Br, 1; Cl, 2) ferroelastic semiconductor possessing dual switching properties of dielectric and second harmonic generation (SHG). Notably, these two hybrids exhibit halogen-regulated ferroelasticity and semiconductor properties. There is a significant difference in Curie temperature (Tc) and X-ray radiation detection sensitivity (S), i.e., the ΔTc and ΔS are 38 K and 87 µC Gyair-1 cm-2, respectively. Meanwhile, crystals 1 and 2 do not show dark current drift in cyclic measurements of different radiation doses with stable switching ratios of 30 and 10, separately. Meanwhile, these results were proven by scientific experimental results and density functional theory (DFT) calculations. Our work presents a facile and practical method to regulate macroproperties on the molecular level, providing a new vision to develop hybrid perovskite ferroic-photoelectric materials.
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Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.
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Ácido Clorogénico , Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Mitocondrias , Estrés Oxidativo , Partenogénesis , Especies Reactivas de Oxígeno , Animales , Estrés Oxidativo/efectos de los fármacos , Partenogénesis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Técnicas de Cultivo de Embriones/veterinaria , Ácido Clorogénico/farmacología , Desarrollo Embrionario/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Blastocisto/efectos de los fármacos , Porcinos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Antioxidantes/farmacología , Femenino , Glutatión/metabolismoRESUMEN
Out-of-plane polarization is a highly desired property of two-dimensional (2D) ferroelectrics for application in vertical sandwich-type photoferroelectric devices, especially in ultrathin ferroelectronic devices. Nevertheless, despite great advances that have been made in recent years, out-of-plane polarization remains unrealized in the 2D hybrid double perovskite ferroelectric family. Here, from our previous work 2D hybrid double perovskite HQERN ((S3HQ)4EuRb(NO3)8, S3HQ=S-3-hydroxylquinuclidinium), we designed a molecular strategy of F-substitution on organic component to successfully obtain FQERN ((S3FQ)4EuRb(NO3)8, S3FQ=S-3-fluoroquinuclidinium) showing circularly polarized luminescence (CPL) response. Remarkably, compared to the monopolar axis ferroelectric HQERN, FQERN not only shows multiferroicity with the coexistence of multipolar axis ferroelectricity and ferroelasticity but also realizes out-of-plane ferroelectric polarization and a dramatic enhancement of Curie temperature of 94â K. This is mainly due to the introduction of F-substituted organic cations, which leads to a change in orientation and a reduction in crystal lattice void occupancy. Our study demonstrates that F-substitution is an efficient strategy to realize and optimize ferroelectric functional characteristics, giving more possibility of 2D ferroelectric materials for applications in micro-nano optoelectronic devices.
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Fenton chemistry-mediated antimicrobials have demonstrated great promise in antibacterial therapy. However, the short life span and diffusion distance of hydroxyl radicals dampen the therapeutic efficiency of these antimicrobials. Herein, inspired by the neutrophil extracellular trap (NET), in which bacteria are trapped and agglutinated via electronic interactions and killed by reactive oxygen species, we fabricated a NET-mimic nanoparticle to suppress bacterial infection in a "trap & kill" manner. Specifically, this NET-mimic nanoparticle was synthesized via polymerization of ferrocene monomers followed by quaternization with a mannose derivative. Similar to the NET, the NET-mimic nanoparticles trap bacteria through electronic and sugar-lectin interactions between their mannose moieties and the lectins of bacteria, forming bacterial agglutinations. Therefore, they confine the spread of the bacteria and restrict the bacterial cells to the destruction range of hydroxyl radicals. Meanwhile, the ferrocene component of the nanoparticle catalyzes the production of highly toxic hydroxyl radicals at the H2O2 rich infection foci and effectively eradicates the agglutinated bacteria. In a mouse model of an antimicrobial-resistant bacteria-infected wound, the NET-mimic nanoparticles displayed potent antibacterial activity and accelerated wound healing.
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Antiinfecciosos , Trampas Extracelulares , Compuestos Ferrosos , Nanopartículas , Ratones , Animales , Neutrófilos , Metalocenos/farmacología , Peróxido de Hidrógeno , Manosa , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , BacteriasRESUMEN
Graph convolutional networks (GCNs) have emerged as a powerful tool for action recognition, leveraging skeletal graphs to encapsulate human motion. Despite their efficacy, a significant challenge remains the dependency on huge labeled datasets. Acquiring such datasets is often prohibitive, and the frequent occurrence of incomplete skeleton data, typified by absent joints and frames, complicates the testing phase. To tackle these issues, we present graph representation alignment (GRA), a novel approach with two main contributions: 1) a self-training (ST) paradigm that substantially reduces the need for labeled data by generating high-quality pseudo-labels, ensuring model stability even with minimal labeled inputs and 2) a representation alignment (RA) technique that utilizes consistency regularization to effectively reduce the impact of missing data components. Our extensive evaluations on the NTU RGB+D and Northwestern-UCLA (N-UCLA) benchmarks demonstrate that GRA not only improves GCN performance in data-constrained environments but also retains impressive performance in the face of data incompleteness.
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Salt stress significantly impedes plant growth and the crop yield. This study utilized de novo transcriptome assembly and ribosome profiling to explore mRNA translation's role in rice salt tolerance. We identified unrecognized translated open reading frames (ORFs), including 42 upstream transcripts and 86 unannotated transcripts. A noteworthy discovery was the role of a small ORF, Ospep5, in conferring salt tolerance. Overexpression of Ospep5 in plants increased salt tolerance, while its absence led to heightened sensitivity. This hypothesis was corroborated by the findings that exogenous application of the synthetic small peptide Ospep5 bolstered salt tolerance in both rice and Arabidopsis. We found that the mechanism underpinning the Ospep5-mediated salt tolerance involves the maintenance of intracellular Na+/K+ homeostasis, facilitated by upregulation of high-affinity potassium transporters (HKT) and Na+/H+ exchangers (SOS1). Furthermore, a comprehensive multiomics approach, particularly ribosome profiling, is instrumental in uncovering unannotated ORFs and elucidating their functions in plant stress responses.
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Arabidopsis , Oryza , Estrés Salino , Tolerancia a la Sal/genética , Perfilación de la Expresión Génica , Sodio/metabolismo , Plantas Tolerantes a la Sal/metabolismo , Transcriptoma , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/metabolismoRESUMEN
Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.
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Gallbladder cancer (GBC) is a highly malignant and rapidly progressing tumor of the human biliary system, and there is an urgent need to develop new therapeutic targets and modalities. Non-POU domain-containing octamer-binding protein (NONO) is an RNA-binding protein involved in the regulation of transcription, mRNA splicing, and DNA repair. NONO expression is elevated in multiple tumors and can act as an oncogene to promote tumor progression. Here, we found that NONO was highly expressed in GBC and promoted tumor cells growth. The dysregulation of RNA splicing is a molecular feature of almost all tumor types. Accordingly, mRNA-seq and RIP-seq analysis showed that NONO promoted exon6 skipping in DLG1, forming two isomers (DLG1-FL and DLG1-S). Furthermore, lower Percent-Spliced-In (PSI) values of DLG1 were detected in tumor tissue relative to the paraneoplastic tissue, and were associated with poor patient prognosis. Moreover, DLG1-S and DLG1-FL act as tumor promoters and tumor suppressors, respectively, by regulating the YAP1/JUN pathway. N6-methyladenosine (m6A) is the most common and abundant RNA modification involved in alternative splicing processes. We identified an m6A reader, IGF2BP3, which synergizes with NONO to promote exon6 skipping in DLG1 in an m6A-dependent manner. Furthermore, IP/MS results showed that RBM14 was bound to NONO and interfered with NONO-mediated exon6 skipping of DLG1. In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment.
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Proteínas de Unión al ADN , Neoplasias de la Vesícula Biliar , Humanos , Proteínas de Unión al ADN/genética , Neoplasias de la Vesícula Biliar/genética , Factores de Transcripción/genética , Empalme del ARN , Proliferación Celular , ARN Mensajero/genética , Línea Celular Tumoral , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Homólogo 1 de la Proteína Discs Large/genética , Homólogo 1 de la Proteína Discs Large/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
OBJECTIVE: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play important regulatory roles in the tumorigenesis and progression of gastric cancer (GC). The aim of this study was to construct the prognostic predictive model of lncRNAs signature and improve the survival prediction of GC. PATIENTS AND METHODS: The expression profiling of lncRNAs in large GC cohorts was performed from The Cancer Genome Atlas (TCGA) databases using the lncRNAs-mining approach, including training data set (N=160) and testing data set (N=159). A 13-lncRNAs signature significantly associated with overall survival (OS) in the training data set was selected. The prognostic value of this 13-lncRNAs signature was then confirmed in the test validation set and the entire validation set, respectively. RESULTS: Based on lncRNA expression profiling of 319 patients with stomach adenocarcinoma (STAD), prognostic 13-lncRNAs signature was found to be significantly associated with the prognosis of GC. Compared to patients with low-risk scores, patients with high-risk scores had a significantly shorter survival time. Moreover, functional enrichment analysis indicated that this 13-lncRNAs signature was potentially involved in multiple biological processes, such as DNA replication and cell cycle signaling pathway. CONCLUSIONS: The prognostic model of the 13-lncRNAs signature established by our study could improve the survival prediction of GC to a greater extent
OBJETIVO: Las pruebas acumuladas demostraron que los ARN no codificantes de larga duración (ARNlC) desempeñaban los importantes papeles reguladores en la tumorigénesis y la progresión del cáncer gástrico (CG). El objetivo de este estudio fue construir el modelo predictivo de pronóstico de la firma de los lncRNA y mejorar la predicción de supervivencia del GC. PACIENTES Y MÉTODOS: El perfil de expresión de los lncARN en grandes cohortes de GC se realizó a partir de las bases de datos del Atlas del Genoma del Cáncer (TCGA) utilizando el enfoque de minería de lncARN, incluyendo el conjunto de datos de entrenamiento (N=160) y el conjunto de datos de pruebas (N=159). Se eligió la firma de 13 lncARN significativamente asociada con la supervivencia general (OS) en la serie de capacitación. El valor pronóstico de esta firma de 13-lncARN se confirmó luego en la serie de validación de pruebas y en toda la serie de validación, respectivamente. RESULTADOS: Basado en el perfil de expresión de lncRNA de 319 pacientes con adenocarcinoma de estómago (STAD), se encontró que la firma de 13-lncRNA de pronóstico estaba significativamente asociada con el pronóstico de GC. En comparación con los pacientes con puntuaciones de bajo riesgo, los pacientes con puntuaciones de alto riesgo tuvieron un tiempo de supervivencia significativamente más corto. Además, el análisis de enriquecimiento funcional indicó que esta firma de 13-lncARN estaba potencialmente involucrada en múltiples procesos biológicos, como la replicación del ADN y la vía de señalización del ciclo celular. CONCLUSIONES: El modelo de pronóstico de la firma de 13-lncARN establecido por nuestro estudio podría mejorar mejor la predicción de supervivencia del GC