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Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2-fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae-gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae-gain type â ¡ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon-intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae-gain type â ¡ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae-gain genetic innovation and sub-functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae.
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BACKGROUND: Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. METHODS: A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. RESULTS: All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. CONCLUSION: ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.
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Aloinjertos , Células Endoteliales , Regeneración Nerviosa , Ratas Sprague-Dawley , Nervio Ciático , Animales , Femenino , Ratas , Nervio Ciático/cirugía , Nervio Ciático/lesiones , Nervio Ciático/trasplante , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/cirugía , Recuperación de la Función , Distribución AleatoriaRESUMEN
Alpha-2-glycoprotein 1, zinc-binding (AZGP1) is a secreted protein, which has been shown to be a potential biomarker of cancer progression; however, its roles in breast cancer are still unclear. Currently, we analyzed the online datasets and found that AZGP1 was highly expressed in breast cancer tissues and its expression was negatively correlated with the survival of breast cancer patients. Functional experiments through AZGP1 knockdown revealed that AZGP1 could promote the proliferation, migration, and invasion ability of breast cancer cells. In vivo experiments obtained a consistent result. Mechanistically, it was found that AZGP1 interacted with tripartite motif-containing protein 25 (TRIM25), which subsequently promoted AZGP1 degradation through facilitating the ubiquitination. Furthermore, overexpression of TRIM25 partially reversed the promoting effects of AZGP1 overexpression on breast cancer progression. Therefore, this study indicates that AZGP1 might be a potential therapeutic target for breast cancer treatment.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Adipoquinas , Glicoproteínas/metabolismo , Proteínas de Motivos Tripartitos/genética , Factores de Transcripción , Ubiquitina-Proteína Ligasas/genética , Zn-alfa-2-GlicoproteínaRESUMEN
Cisplatin, a potent chemotherapy agent, is highly effective against various cancers but is hindered by resistance and toxicities. This study aims to investigate the roles of SLC7A11, a cystine/glutamate transporter, in cisplatin resistance, and explored Tanshinone IIA as a therapeutic option. Cisplatin reduced SLC7A11 in renal cells, worsening toxicity. Cisplatin-resistant gastric cancer cells show increased SLC7A11, driving resistance, while SLC7A11 knockdown curbed resistance. Tanshinone IIA showed promise in alleviating cisplatin toxicity by enhancing SLC7A11 expression and reducing associated adverse effects, while it effectively reversed cisplatin resistance in gastric cancer cells by suppressing SLC7A11. Additionally, Tanshinone IIA counteracted cisplatin resistance by inhibiting PIAS4-mediated SUMOylation of SLC7A11. Simultaneously, overexpressing miR-375, which has been shown to target SLC7A11, exacerbated cisplatin toxicity via SLC7A11 downregulation, which Tanshinone IIA attenuates. In summary, our study unveils complex SLC7A11 regulation in cisplatin resistance and toxicity. Tanshinone IIA emerges as a promising modulator of SLC7A11 through individual pathways, offering novel insights into overcoming cisplatin resistance and reducing toxicities in cancer therapy.
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Cisplatino , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Línea Celular Tumoral , Abietanos/farmacología , Sistema de Transporte de Aminoácidos y+RESUMEN
Cytochrome P450 (CYP) 4Z1 (CYP4Z1) has recently garnered much interest as its expression predicts a poor prognosis and as a oncogene in breast cancer, and overexpressed in other many cancers. We previously showed that CYP4Z1 acts as a promoter of cancer stem cells (CSCs) to facilitate the occurrence and development of breast cancer. Here, RNA sequencing found that 1-benzylimidazole (1-Benzy) held a preferable correlation with breast cancer and suppressed the expression of CSC makers. Further functional experiments, including mammary spheroid formation, wound-healing, transwell-invasion, detection of tumor initiation, and metastatic ability, showed that 1-Benzy suppressed the stemness and metastasis of breast cancer cells. Additionally, we further demonstrated that CYP4Z1 is necessary for 1-Benzy-mediated suppression on breast cancer stemness and 1-Benzy exerted a weaker effect in breast cancer cells with CYP4Z1 knockdown. Taken together, our data suggest that 1-Benzy might be a potential drug suppressing breast cancer stemness via targeting CYP4Z1.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Imidazoles , Línea Celular TumoralRESUMEN
Advancement of wearable microelectronics demands their power source with continuous energy supply, skin-integration and miniaturization. In light of poly (vinyl alcohol) (PVA) hydrogel with nontoxicity, good biocompatibility and low cost, an advanced wearable PVA-based hybrid biofuel cells (HBFCs) with high self-adhesiveness was developed. Through the reaction between PVA molecules and succinic anhydride (SAA), the carboxylated PVA (PVA/SAA) was obtained, and by incorporation with PDA as crosslinker, the self-adhesive PVA/SAA-DA hydrogel electrolytes formed by dual covalent and hydrogen bonding. With increasing SAA and PDA content, the pore size decreased, and a uniform and dense network formed, endowing the hydrogel with a relatively high absorption capacity of PBS solution of lactate as cell fuel. Meanwhile the various functional groups of hydrogel, including catechol, quinone, amino and hydroxyl groups, contributed to impressive tissue adhesion strength against pigskin under dry and wet conditions. The PVA/SAA-DA hydrogel displayed high conductive property, and the integrated PVA-based HBFC generated open circuit voltage of 0.50 V and maximum power density of 128.76 µW/cm2 in 20 mM lactate solution, which was optimized to be 0.57 V/224.85 µW/cm2 when the pore size was enlarged. The power retention reached above 70% in one week, showing long-term stability of HBFC. The PVA-based HBFC was further adhered to human skin without extra adhesive tapes to scavenge human sweat as biofuel, and the maximum power density reached 85.34 µW/cm2, while by connected with a DC-DC converter, the HBFC could power watch, exhibiting promising application potentials as wearable electronic device to provide bioelectricity.
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Fuentes de Energía Bioeléctrica , Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Humanos , Biocombustibles , Cementos de Resina , Alcohol Polivinílico , Adhesivos , Hidrogeles , Etanol , LactatosRESUMEN
IMPORTANCE: Epidemiological data reveal that FAdV-4 and FAdV-8a are the dominant serotypes of FAdVs in the poultry industry in China. Although three commercial inactivated vaccines against FAdV-4 have been licensed in China, the bivalent vaccine against both FAdV-4 and FAdV-8a is not available. Here, we used CRISPR-Cas9 and Cre-LoxP system to generate a recombinant virus FAdV4-F/8a-rF2 expressing the Fiber of FAdV-8a. Notably, FAdV4-F/8a-rF2 was highly attenuated and could provide efficient protection against both FAdV-4 and FAdV-8a in the chicken infection model, highlighting the applaudable application of FAdV4-F/8a-rF2 as a novel live-attenuated bivalent vaccine against the diseases caused by the infection of FAdV-4 and FAdV-8a.
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Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Serogrupo , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/veterinaria , Aviadenovirus/genética , Pollos , Vacunas CombinadasRESUMEN
To explore the expression and prognosis of Fc fragment of IgG low affinity IIb receptor (FCGR2B) in glioma and its relationship with immune microenvironment, so as to provide potential molecular targets for the treatment of glioma. We analyzed the gene expression of FCGR2B using the Cancer Genome Atlas database, Chinese Glioma Genome Atlas, Gene Expression Omnibus database and other glioma related databases. Moreover, we generated survival receiver operating characteristic curve, carried out univariate and multivariate Cox analysis and nomograph construction, and analyzed the relationship between FCGR2B and prognosis. According to the median of FCGR2B gene expression value, the differential expression analysis was carried out by high and low grouping method, and the gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis enrichment analysis were carried out to explore the possible mechanism. Then, the correlation between immune score of glioma and prognosis, World Health Organization grade and FCGR2B expression was analyzed. Finally, the correlation between FCGR2B expression and the proportion of tumor infiltrating immune cells, immune checkpoints, tumor mutation load and immune function was analyzed. The expression of FCGR2B in gliomas was higher than that in normal tissues and was associated with poor prognosis. Independent prognostic analysis showed that FCGR2B was an independent prognostic factor for glioma. The analysis of gene ontology and gene set enrichment analysis showed that FCGR2B was closely related to immune-related functions. The analysis of immune scores and prognosis, World Health Organization grade and FCGR2B expression in gliomas indicated that patients with high immune scores had significantly poorer overall survival and higher tumor pathological grade. In addition, immune scores were significantly positively correlated with the expression of FCGR2B. The analysis of tumor infiltrating immune cells suggested that the expression level of FCGR2B affected the immune activity of TME. In addition, the expression of FCGR2B was positively correlated with almost all immune checkpoint molecules including CD28, CD44, TNFSF14, PDCD1LG2, LAIR1, and CD48 and was significantly positively correlated with tumor mutation load. All immunobiological functions of the high expression group of FCGR2B were significantly inhibited. FCGR2B may play an important role in the occurrence, development and invasion of tumor by influencing the tumor microenvironment of immunosuppression. FCGR2B may be an important target for the treatment of glioma.
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Glioma , Microambiente Tumoral , Humanos , Pueblo Asiatico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Antígenos CD28 , Glioma/genética , Glioma/inmunología , Pronóstico , Receptores de IgG/genética , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Fruit size and shape are controlled by genes expressed during the early developmental stages of fruit. Although the function of ASYMMETRIC LEAVES 2 (AS2) in promoting leaf adaxial cell fates has been well characterized in Arabidopsis thaliana, the molecular mechanisms conferring freshy fruit development as a spatial-temporal expression gene in tomato pericarp remain unclear. In the present study, we verified the transcription of SlAS2 and SlAS2L, two homologs of AS2, in the pericarp during early fruit development. Disruption of SlAS2 or SlAS2L caused a significant decrease in pericarp thickness as a result of a reduction in the number of pericarp cell layers and cell area, leading to smaller tomato fruit size, which revealed their critical roles in tomato fruit development. In addition, leaves and stamens exhibited severe morphological defects in slas2 and slas2l single mutants, as well as in the double mutants. These results demonstrated the redundant and pleiotropic functions of SlAS2 and SlAS2L in tomato fruit development. Yeast two-hybrid and split-luciferase complementation assays showed that both SlAS2 and SlAS2L physically interact with SlAS1. Molecular analyses further indicated that SlAS2 and SlAS2L regulate various downstream genes in leaf and fruit development, and that some genes participating in the regulation of cell division and cell differentiation in the tomato pericarp are affected by these genes. Our findings demonstrate that SlAS2 and SlAS2L are vital transcription factors required for tomato fruit development.
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Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
FOXP3+ regulatory T (Treg) cells play critical roles in establishing the immunosuppressive tumour microenvironment, which is achieved and dynamically maintained with the contribution of various stromal and immune cell subsets. However, the dynamics of non-lymphoid FOXP3+ Treg cells and the mutual regulation of Treg cells and other cell types in solid tumour microenvironment remains largely unclear. In this review, we summarize the latest findings on the dynamic connections and reciprocal regulations of non-lymphoid Treg cell subsets in accordance with well-established and new emerging hallmarks of cancer, especially on the immune escape of tumour cells in solid tumours. Our comprehension of the interplay between FOXP3+ Treg cells and key hallmarks of cancer may provide new insights into the development of next-generation engineered T cell-based immune treatments for solid tumours.
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Neoplasias , Linfocitos T Reguladores , Humanos , Neoplasias/terapia , Neoplasias/metabolismo , Factores de Transcripción Forkhead/metabolismo , Microambiente TumoralRESUMEN
Shoot branching is fundamentally important in determining soybean yield. Here, through genome-wide association study, we identify one predominant association locus on chromosome 18 that confers soybean branch number in the natural population. Further analyses determine that Dt2 is the corresponding gene and the natural variations in Dt2 result in significant differential transcriptional levels between the two major haplotypes. Functional characterization reveals that Dt2 interacts with GmAgl22 and GmSoc1a to physically bind to the promoters of GmAp1a and GmAp1d and to activate their transcription. Population genetic investigation show that the genetic differentiation of Dt2 display significant geographic structure. Our study provides a predominant gene for soybean branch number and may facilitate the breeding of high-yield soybean varieties.
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Estudio de Asociación del Genoma Completo , Glycine max , Glycine max/genética , Fitomejoramiento , Haplotipos , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Foxp3+ regulatory T (Treg) cells facilitate tumor immune evasion by forming a suppressive tumor microenvironment. Therefore, immune therapies promoting Treg fragility may greatly enhance immune checkpoint blockade (ICB) efficacy in cancers. METHODS: We have screened 2640 compounds and identified the gut microbial metabolite gallic acid, which promotes Foxp3 degradation and Treg instability by repressing Usp21 gene transcription. In vivo and in vitro experiments have been performed to explore the roles of Usp21 in Treg cells. Importantly, we treated tumor-bearing mice with gallic acid and anti-PD-1 antibody to explore the potential therapeutic value of gallic acid in clinical cancer immunotherapy. RESULTS: Mechanistically, gallic acid prevents STAT3 phosphorylation and the binding of phosphorylated STAT3 to Usp21 gene promoter. The deubiquitinated Usp21 and stabilized PD-L1 proteins boost the function of Treg cells. Combination of gallic acid and anti-PD-1 antibody, in colorectal cancer (CRC) treatment, not only significantly dampen Treg cell function by impairing PD-L1/PD-1 signaling and downregulating Foxp3 stability, but also promote CD8+ T cells' production of IFN-γ and limited tumor growth. CONCLUSION: Our findings have implications for improving the efficacy of ICB therapy in CRC by inducing T-helper-1-like Foxp3lo Treg cells.
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Antígeno B7-H1 , Neoplasias , Animales , Linfocitos T CD8-positivos , Factores de Transcripción Forkhead/metabolismo , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ratones , Microambiente TumoralRESUMEN
Seed size is one of the most important agronomic traits determining the yield of crops. Cloning the key genes controlling seed size and pyramiding their elite alleles will facilitate yield improvement. To date, few genes controlling seed size have been identified in soybean, a major crop that provides half of the plant oil and one quarter of the plant protein globally. Here, through a genome-wide association study of over 1800 soybean accessions, we determined that natural allelic variation at GmST05 (Seed Thickness 05) predominantly controlled seed thickness and size in soybean germplasm. Further analyses suggested that the two major haplotypes of GmST05 differed significantly at the transcriptional level. Transgenic experiments demonstrated that GmST05 positively regulated seed size and influenced oil and protein contents, possibly by regulating the transcription of GmSWEET10a. Population genetic diversity analysis suggested that allelic variations of GmST05 were selected during geographical differentiation but have not been fixed. In summary, natural variation in GmST05 determines transcription levels and influences seed size and quality in soybean, making it an important gene resource for soybean molecular breeding.
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Alelos , Estudio de Asociación del Genoma Completo , Glycine max/genética , Semillas/anatomía & histología , Semillas/genética , Clonación Molecular , Variación Genética , Haplotipos , Polimorfismo de Nucleótido Simple , Glycine max/crecimiento & desarrolloRESUMEN
Neobavaisoflavone (NBIF), a monomolecular compound extracted from Psoralea corylifolia (Leguminosae), is commonly used in traditional Chinese medicine for multiple purposes. NBIF is known to exert anti-fungal and anti-tumor effects, and promote bone formation. Whether NBIF exhibits anti-allergic effects by regulating mast cell activation remains unclear. Therefore, we designed this study to investigate the anti-allergic effects of NBIF on IgE/Ag-induced mouse bone marrow-derived mast cells and ovalbumin-induced asthma, and the passive systemic anaphylaxis (PSA) reaction in mice. Our results showed that NBIF suppresses the production of leukotriene C4, prostaglandin D2 and inflammatory cytokines, and decreases the degranulation of BMMCs stimulated by IgE/Ag. A thorough investigation ascertained that NBIF suppresses the phosphorylation of mitogen-activated protein kinases, and represses the nuclear factor-κB-related signaling pathway. In addition, the oral administration of NBIF in mice inhibited the IgE-induced PSA reaction in a dose-dependent manner. Overall, we provide new insights into how NBIF regulates the IgE/Ag-mediated signaling pathways. Moreover, our investigation promotes the potential use of NBIF in treating allergy and asthma.
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Anafilaxia , Antialérgicos , Asma , Hipersensibilidad , Anafilaxia/tratamiento farmacológico , Animales , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Asma/tratamiento farmacológico , Asma/metabolismo , Degranulación de la Célula , Hipersensibilidad/tratamiento farmacológico , Inmunoglobulina E/metabolismo , Isoflavonas , Mastocitos , Ratones , Ratones Endogámicos BALB CRESUMEN
The CD4+FOXP3+ regulatory T (Treg) cells are essential for maintaining immune homeostasis in healthy individuals. Results from clinical trials of Treg cell-based therapies in patients with graft versus host disease (GVHD), type 1 diabetes (T1D), liver transplantation, and kidney transplantation have demonstrated that adoptive transfer of Treg cells is emerging as a promising strategy to promote immune tolerance. Here we provide an overview of recent progresses and current challenges of Treg cell-based therapies. We summarize the completed and ongoing clinical trials with human Treg cells. Notably, a few of the chimeric antigen receptor (CAR)-Treg cell therapies are currently undergoing clinical trials. Meanwhile, we describe the new strategies for engineering Treg cells used in preclinical studies. Finally, we envision that the use of novel synthetic receptors, metabolic regulators, combined therapies, and in vivo generated antigen-specific or engineered Treg cells through the delivery of modified mRNA and CRISPR-based gene editing will further promote the advances of next-generation Treg cell therapies.
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Enfermedad Injerto contra Huésped , Linfocitos T Reguladores , Traslado Adoptivo , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/terapia , Humanos , Inmunoterapia Adoptiva/métodosRESUMEN
Soybean is one of the most important oilseed and fodder crops. Benefiting from the efforts of soybean breeders and the development of breeding technology, large number of germplasm has been generated over the last 100 years. Nevertheless, soybean breeding needs to be accelerated to meet the needs of a growing world population, to promote sustainable agriculture and to address future environmental changes. The acceleration is highly reliant on the discoveries in gene functional studies. The release of the reference soybean genome in 2010 has significantly facilitated the advance in soybean functional genomics. Here, we review the research progress in soybean omics (genomics, transcriptomics, epigenomics and proteomics), germplasm development (germplasm resources and databases), gene discovery (genes that are responsible for important soybean traits including yield, flowering and maturity, seed quality, stress resistance, nodulation and domestication) and transformation technology during the past decade. At the end, we also briefly discuss current challenges and future directions.
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Glycine max , Fitomejoramiento , Productos Agrícolas/genética , Genoma de Planta/genética , Genómica , Glycine max/genéticaRESUMEN
OBJECTIVE: To analyze missed rib fractures and proper time for evaluation on CT at different ages and to determine factors that favor missed fractures. METHODS: One hundred patients with rib fractures who underwent CT were classified into three groups according to their age: young, middle-aged, and elderly. CT was performed within 1 to 6 weeks after trauma. The imaging features and temporal changes of rib fractures were analyzed. RESULTS: At the first CT during the initial week, 638 ribs were detected with one or several fractures, overall 838 fractures were confirmed, and 6 were suspected. In the next 2-6 weeks, 47 occult rib fractures were additionally detected. The number of additionally diagnosed fractures was the highest in respectively the 3rd week among younger, 4th week in the middle-aged, and 6th week in the elderly groups. The detection of occult rib fractures was significantly delayed in the middle-aged and elderly groups compared with the young group (p < 0.05). The time to form bony callus was also significantly (p < 0.05) delayed with age, with significantly (p < 0.05) more time needed to form bony callus in the middle-aged (23.8 ± 4.5 days) and elderly (28.48 ± 5.1 days) groups than in the young group (18.0 ± 2.2 days). CONCLUSIONS: Most rib fractures can be detected within the first week after trauma. Detection of occult rib fractures will be delayed with increase of age, and repeated CT scanning should be appropriately postponed in patients at different ages. Trabecula, inner and outer plates, costal angle, and cartilage are the primary locations for occult and subtle fractures which should be carefully evaluated. KEY POINTS: ⢠More rib fractures can be detected on repeated CT scans, especially for subtle and occult rib fractures. ⢠Detection of all rib fractures helps relieve the patient's concerns and determine the degree of personal injury for appropriate evaluation.
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Fracturas de las Costillas , Heridas no Penetrantes , Anciano , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de las Costillas/diagnóstico por imagen , Costillas , Tomografía Computarizada por Rayos XRESUMEN
Neuronostatin (NST) is an endogenous peptide hormone, it has the ability to improve oligomeric Aß (oAß)-induced cognitive impairments and increase blood glucose levels in mice. However, the relationship between NST and oAß regarding brain glucose metabolism has not yet been established. The present study defined the contributions of NST and oAß in the brain glucose metabolism in mice. It was found that i.c.v. co-administration of NST (3 nmol/mouse) and oAß (1 nmol/mouse) decreased the mRNA expressions of glucose-6-phosphate dehydrogenase and phosphofructokinase. The treatments were observed to reduce ATP production and the enzyme activities of glucose-6-phosphate dehydrogenase and hexokinase in both the cortex and hippocampus. Simultaneously, co-injection of NST and oAß inhibited the mRNA and protein expression of glucose transporters GLUT3 and GLUT1 in the cortex and hippocampus. NST promoted the oAß-induced decreased the cortical NeuN staining, while oAß increased the levels of NST in both the cortex and hippocampus. I.c.v. co-administration of NST and oAß led to increase the levels of GPR107 expression and the phosphorylation of PKA, Akt, PERK and eIF-2α in the cortex. These findings suggest that NST promoted oAß-induced dysfunctional glucose metabolism through the GPR107/PKA/Akt signaling pathway and PERK/eIF2α axis in the brain, which thus contributes to metabolic dysfunction and Alzheimer's disease (AD) pathophysiology.
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Péptidos beta-Amiloides/farmacología , Corteza Cerebral/metabolismo , Glucosa/metabolismo , Hipocampo/metabolismo , Fragmentos de Péptidos/farmacología , Hormonas Peptídicas/farmacología , Adenosina Trifosfato/metabolismo , Péptidos beta-Amiloides/química , Animales , Combinación de Medicamentos , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Glucólisis/efectos de los fármacos , Hexoquinasa/metabolismo , Masculino , Ratones , Fragmentos de Péptidos/química , Fosfofructoquinasas/metabolismo , Multimerización de Proteína , Transducción de Señal/fisiologíaRESUMEN
RNA-binding protein (RBP) has a highly dynamic spatiotemporal regulation process and important biological functions. They are critical to maintain the transcriptome through post-transcriptionally controlling the processing and transportation of RNA, including regulating RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation. Alteration of each process will affect the RNA life cycle, produce abnormal protein phenotypes, and thus lead to the occurrence and development of tumors. Here, we summarize RBPs involved in tumor progression and the underlying molecular mechanisms whereby they are regulated and exert their effects. This analysis is an important step towards the comprehensive characterization of post-transcriptional gene regulation involved in tumor progression.
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Proteínas de Neoplasias/fisiología , Neoplasias/patología , ARN Neoplásico/metabolismo , Proteínas de Unión al ARN/fisiología , Empalme Alternativo , Ensamble y Desensamble de Cromatina , Daño del ADN , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Poliadenilación , Biosíntesis de Proteínas , Procesamiento Proteico-Postraduccional , Procesamiento Postranscripcional del ARN , Empalme del ARN , Estabilidad del ARN , ARN no Traducido/metabolismo , Proteínas de Unión al ARN/química , Fracciones Subcelulares/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: Anterior cruciate ligament (ACL) injury can cause damage to the meniscus and articular cartilage, and may even lead to osteoarthritis. This study aimed to analyze the accuracy and feasibility of magnetic resonance imaging (MRI) imaging signs in the diagnosis of knee joint ACL injury. METHODS: A total of 78 patients admitted to our hospital from June 2018 to October 2019 with highly suspected ACL injury were selected for this prospective study. We used MRI and arthroscopy to diagnose the ACL injuries, and the results of MRI and arthroscopy, as well as the value of MRI in diagnosing ACL injury, were compared. RESULTS: Among the 78 participants, 66 cases were diagnosed with ACL injury (28 with complete tear, 38 with partial tear), and 12 were normal according to arthroscopy. Among the 66 cases with ACL injury, 63 (95.45%) were confirmed by MRI detection. The sensitivity, specificity, and accuracy of MRI in the diagnosis of ACL injury were 95.45% (63/66), 91.67%, and 94.87%, respectively. The accuracy of MRI in the diagnosis of complete and partial tears were 92.86% and 94.74%, respectively. Among the four direct MRI signs of ACL injury, the differences in interruption of ACL continuity, thickening and edema, and abnormal walking were statistically significant (P<0.05). Among the 8 indirect MRI signs, all showed high specificity and low sensitivity, and which the specificity of posterior cruciate ligament index, Notch sign, meniscus exposure sign of posterior ankle, and lateral collateral ligament monolayer display showed higher specificity (P<0.05). CONCLUSIONS: Examination with MRI offers high accuracy in the diagnosis of ACL injury, and has good consistency with arthroscopic diagnosis, which can provide reliable guidance for the selection and formulation of clinical surgery plans, and might be used as the first choice for the non-traumatic diagnosis of ACL injury.