RESUMEN
Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.
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Inmunoterapia , Neoplasias , ARN Circular , Microambiente Tumoral , ARN Circular/genética , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia/métodos , Animales , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , MicroARNs/genéticaRESUMEN
Vacuolar H+ -ATPase (V-ATPase) has diverse functions related to plant development and growth. It creates the turgor pressure that drives cell growth by generating the energy needed for the active transport of solutes across the tonoplast. V-ATPase is a large protein complex made up of multiheteromeric subunits, some of which have unknown functions. In this study, a forward genetics-based strategy was employed to identify the vab3 mutant, which displayed resistance to isoxaben, a cellulose synthase inhibitor that could induce excessive transverse cell expansion. Map-based cloning and genetic complementary assays demonstrated that V-ATPase B subunit 3 (VAB3) is associated with the observed insensitivity of the mutant to isoxaben. Analysis of the vab3 mutant revealed defective ionic homeostasis and hypersensitivity to salt stress. Treatment with a V-ATPase inhibitor exacerbated ionic tolerance and cell elongation defects in the vab3 mutant. Notably, exogenous low-dose Ca2+ or Na+ could partially restore isoxaben resistance of the vab3 mutant, suggesting a relationship between VAB3-regulated cell growth and ion homeostasis. Taken together, the results of this study suggest that the V-ATPase subunit VAB3 is required for cell growth and ion homeostasis in Arabidopsis.
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Arabidopsis , ATPasas de Translocación de Protón Vacuolares , Arabidopsis/metabolismo , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , Benzamidas/farmacología , Benzamidas/metabolismo , HomeostasisRESUMEN
The transport of circovirus capsid protein into nucleus is essential for viral replication in infected cell. However, the role of nucleolar shuttle proteins during porcine circovirus 3 capsid protein (PCV3 Cap) import is still not understood. Here, we report a previously unidentified nucleolar localization signal (NoLS) of PCV3 Cap, which hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate nucleolar localization of PCV3 Cap. The NoLS of PCV3 Cap and serine-48 residue of N-terminal oligomerization domain of NPM1 are essential for PCV3 Cap/NPM1 interaction. In addition, charge property of serine-48 residue of NPM1 is critical for nucleolar localization and interaction with PCV3 Cap. Taken together, our findings demonstrate for the first time that NPM1 interacts with PCV3 Cap and is responsible for its nucleolar localization.
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Proteínas de la Cápside/metabolismo , Circovirus/metabolismo , Proteínas Nucleares/metabolismo , Animales , Sitios de Unión , Proteínas de la Cápside/genética , Línea Celular , Circovirus/genética , Electroforesis en Gel de Poliacrilamida , Técnicas de Silenciamiento del Gen , Immunoblotting , Microscopía Confocal , Nucleofosmina , Serina , PorcinosRESUMEN
Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe (λex = 633 nm, λem = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.
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Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/química , Colorantes Fluorescentes/química , Nanopartículas del Metal/química , Mitocondrias/metabolismo , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carbono/química , Carbono/toxicidad , Línea Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Colorantes Fluorescentes/toxicidad , Glutatión/metabolismo , Oro/química , Oro/toxicidad , Humanos , Nanopartículas del Metal/toxicidad , Ratones , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Compuestos Organofosforados/química , Compuestos Organofosforados/toxicidad , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Plata/química , Plata/toxicidadRESUMEN
A redox-responsive chemodynamic therapy (CDT)-based theranostic system composed of hollow mesoporous MnO2 (H-MnO2), doxorubicin (DOX), and fluorescent (FL) carbon nanodots (CDs) is reported for the diagnosis and therapy of cancer. In general, since H-MnO2 can be degraded by intracellular glutathione (GSH) to form Mn2+ with excellent Fenton-like activity to generate highly reactive ·OH, the normal antioxidant defense system can be injured via consumption of GSH. This in turn can potentiate the cytotoxicity of CDT and release DOX. The cancer cells can be eliminated effectively by the nanoplatform via the synergistic effect of chemotherapy and CDT. The FL of CDs can be restored after H-MnO2 is degraded which blocked the fluorescence resonance energy transfer process between CDs as an energy donor and H-MnO2 as an FL acceptor. The GSH can be determined by recovery of the FL and limit of detection is 1.30 µM with a linear range of 0.075-0.825 mM. This feature can be utilized to efficiently distinguish cancerous cells from normal ones based on different GSH concentrations in the two types of cells. As a kind of CDT-based theranostic system responsive to GSH, simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) in a single nanoplatform can be achieved. The redox-responsive chemodynamic therapy (CDT)-based theranostic system is fabricated by H-MnO2, DOX, and fluorescent CDs. The nanoplatform can realize simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) to improve the therapeutic efficiency and security.
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Antineoplásicos/farmacología , Doxorrubicina/farmacología , Colorantes Fluorescentes/química , Glutatión/análisis , Medicina de Precisión/métodos , Puntos Cuánticos/química , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carbono/química , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/química , Liberación de Fármacos , Quimioterapia , Humanos , Límite de Detección , Ratones , Molibdeno/química , Neoplasias/diagnóstico , Óxidos/química , Espectrometría de FluorescenciaRESUMEN
KEY MESSAGE: A new synthetic auxin AAL1 with new structure was identified. Different from known auxins, it has weak effects. By AAL1, we found specific amino acids could restore the effects of auxin with similar structure. Auxin, one of the most important phytohormones, plays crucial roles in plant growth, development and environmental response. Although many critical regulators have been identified in auxin signaling pathway, some factors, especially those with weak fine-tuning roles, are still yet to be discovered. Through chemical genetic screenings, we identified a small molecule, Auxin Activity Like 1 (AAL1), which can effectively inhibit dark-grown Arabidopsis thaliana seedlings. Genetic screening identified AAL1 resistant mutants are also hyposensitive to indole-3-acetic acid (IAA) and 2,4-dichlorophenoxyacetic acid (2,4-D). AAL1 resistant mutants such as shy2-3c and ecr1-2 are well characterized as mutants in auxin signaling pathway. Genetic studies showed that AAL1 functions through auxin receptor Transport Inhibitor Response1 (TIR1) and its functions depend on auxin influx and efflux carriers. Compared with known auxins, AAL1 exhibits relatively weak effects on plant growth, with 20 µM and 50 µM IC50 (half growth inhibition chemical concentration) in root and hypocotyl growth respectively. Interestingly, we found the inhibitory effects of AAL1 and IAA could be partially restored by tyrosine and tryptophan respectively, suggesting some amino acids can also affect auxin signaling pathway in a moderate manner. Taken together, our results demonstrate that AAL1 acts through auxin signaling pathway, and AAL1, as a weak auxin activity analog, provides us a tool to study weak genetic interactions in auxin pathway.
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Arabidopsis/metabolismo , Hidrocarburos Aromáticos/metabolismo , Ácidos Indolacéticos/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Hidrocarburos Aromáticos/farmacología , Luz , Redes y Vías Metabólicas , Estructura Molecular , Mutación , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Plantones , Transducción de SeñalRESUMEN
Circular RNAs (circRNAs) are a novel class of non-coding RNA that assumes a covalently closed continuous conformation. CircRNAs were previously thought to be the byproducts of splicing errors caused by low abundance and the technological limitations. With the recent development of high-throughput sequencing technology, numerous circRNAs have been discovered in many species. Recent studies have revealed that circRNAs are stable and widely expressed, and often exhibit cell type-specific or tissue-specific expression. Most circRNAs can be generated from exons, introns, or both. Remarkably, emerging evidence indicates that some circRNAs can serve as microRNA (miRNA) sponges, regulate transcription or splicing, and can interact with RNA binding proteins (RBPs). Moreover, circRNAs have been reported to play essential roles in myriad life processes, such as aging, insulin secretion, tissue development, atherosclerotic vascular disease risk, cardiac hypertrophy and cancer. Although circRNAs are ancient molecules, they represent a newly appreciated form of noncoding RNA and as such have great potential implications in clinical and research fields. Here, we review the current understanding of circRNA classification, function and significance in physiological and pathological processes. We believe that future research will increase our understanding of the regulation and function of these novel molecules.
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Aterosclerosis/genética , Cardiomegalia/genética , MicroARNs/genética , Neoplasias/genética , Empalme del ARN , ARN/genética , Aterosclerosis/diagnóstico , Aterosclerosis/metabolismo , Aterosclerosis/patología , Emparejamiento Base , Biomarcadores/metabolismo , Cardiomegalia/diagnóstico , Cardiomegalia/metabolismo , Cardiomegalia/patología , Exones , Humanos , Intrones , MicroARNs/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/patología , ARN/clasificación , ARN/metabolismo , ARN CircularRESUMEN
The nonstructural protein 2 (NS2) of classical swine fever virus (CSFV) is a self-splicing ribozyme wherein the precursor protein NS2-3 is cleaved, and the cleavage efficiency of NS2-3 is crucial to the replication of viral RNA. However, the proteolytic activity of NS2 autoprotease may be achieved through a cellular chaperone called J-domain protein interacting with viral protein (Jiv) or its fragment Jiv90, as evidence suggests that Jiv is required for the proper functioning of the NS2 protein of bovine viral diarrhea virus. Hence, the expression of Jiv may be correlated with the replication efficiency of CSFV RNA. We investigated the expression levels of Jiv and viral RNA in CSFV-infected cells and tissues using Real-time RT-PCR or Western blot analysis. The obtained results show that Jiv90 possibly plays an important role in the lifecycle of CSFV because the distribution of Jiv90 protein shows a positive correlation with the viral load of CSFV. Furthermore, the overexpression or knockdown of Jiv90 in swine cells can also significantly promote or decrease the viral load, respectively. The detection of Flow cytometry shows that the overexpression of Jiv90 prolongs the G1 phase of cell cycles but has no effect on apoptosis. These findings are likely to be of benefit in clarifying the pathogenesis of the CSFV.
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Virus de la Fiebre Porcina Clásica/genética , Peste Porcina Clásica/virología , Chaperonas Moleculares/genética , ARN Viral/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/fisiología , Animales , Apoptosis , Ciclo Celular , Línea Celular , Virus de la Diarrea Viral Bovina/genética , Virus de la Diarrea Viral Bovina/metabolismo , Fase G1 , Técnicas de Silenciamiento del Gen , Interacciones Huésped-Patógeno , Lentivirus/genética , Lentivirus/fisiología , Dominios y Motivos de Interacción de Proteínas , ARN Mensajero , Porcinos , Carga Viral , Proteínas Virales/genética , Proteínas Virales/fisiología , Replicación ViralRESUMEN
BACKGROUND/AIMS: Circular RNAs (circRNAs) are a special novel type of a stable, diverse and conserved noncoding RNA in mammalian cells. Particularly in cancer, circRNAs have been reported to be widely involved in the physiological/pathological process of life. However, it is unclear whether circRNAs are specifically involved in pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated the expression profile of circRNAs in six PDAC cancer samples and paired adjacent normal tissues using microarray. A high-throughput circRNA microarray was used to identify dysregulated circular RNAs in six PDAC patients. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. RESULTS: We revealed and confirmed that a number of circRNAs were dysregulated, which suggests a potential role in pancreatic cancer. CONCLUSIONS: this study demonstrates that clusters of circRNAs are aberrantly expressed in PDAC compared with normal samples and provides new potential targets for the future treatment of PDAC and novel insights into PDAC biology.
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Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias Pancreáticas/genética , ARN/genética , Adulto , Anciano , Secuencia de Bases , Femenino , Ontología de Genes , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Anotación de Secuencia Molecular , ARN/metabolismo , ARN Circular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Transducción de Señal/genéticaRESUMEN
Long noncoding RNAs (lncRNAs) have been shown to play critical roles in the development and progression of diseases. lncRNA activated by transforming growth factor beta (TGF-ß) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in pancreatic cancer. This study aimed to assess lncRNA-ATB expression in pancreatic cancer and explore its role in pancreatic cancer pathogenesis. Quantitative real-time polymerase chain reaction was performed to detect lncRNA-ATB expression in 150 pancreatic cancer tissues and five pancreatic cancer cell lines compared to paired adjacent normal tissues and normal human pancreatic ductal epithelial cell line HPDE6c-7. The correlations between lncRNA-ATB expression and clinicopathological characteristics and prognosis were also analyzed. We found that lncRNA-ATB expression was decreased in pancreatic cancer tissues and pancreatic cancer cell lines. Low lncRNA-ATB expression levels were significantly correlated with lymph node metastases (yes vs. no, P = 0.009), neural invasion (positive vs. negative, P = 0.049), and clinical stage (early stage vs. advanced stage, P = 0.014). Moreover, patients with low lncRNA-ATB expression levels exhibited markedly worse overall survival prognoses (P < 0.001). Multivariate analysis indicated that decreased lncRNA-ATB expression was an independent predictor of poor prognosis in pancreatic cancer patients (P = 0.005). In conclusion, lncRNA-ATB may play a critical role in pancreatic cancer progression and prognosis and may serve as a potential prognostic biomarker in pancreatic cancer patients.
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Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/genética , Factor de Crecimiento Transformador beta/genética , Línea Celular , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/estadística & datos numéricosRESUMEN
Due to high incidence of invasion and intrahepatic metastasis, hepatocellular carcinoma (HCC) is one of the most aggressive tumors in the world, which is also associated with the acquisition of epithelial-mesenchymal transition (EMT). Increasing evidence suggests that cancer cells with EMT traits share many biological characteristics with cancer stem cells. And miR-200a has been known as a powerful regulator of EMT. Here, we sought to investigate the role of miR-200a in regulation of EMT phenotype of liver cancer stem cells (LCSCs). We used side population (SP) sorting to obtain cancer stem-like cells from HCC cell lines and identified that the SP fraction could be enriched with LCSCs. Then, we detected the expression of miR-200a and EMT makers in SP and non-SP cells. Our results suggested that miR-200a was down-regulated in SP cells, along with relatively low epithelial marker and high mesenchymal marker. In order to find the role of miR-200a in the manipulation of EMT, we transfected miR-200a mimic into LCSCs and found that overexpression of miR-200a resulted in down-regulation of N-cadherin, ZEB2, and vimentin, but up-regulation of E-cadherin. Moreover, overexpression of miR-200a resulted in decreased migration and invasion ability in LCSCs. In conclusion, our study revealed that miR-200a played an important role in linking the characteristics of cancer stem cells with EMT phenotype in HCC, and targeting miR-200a might be an effective strategy to weaken the invasive behavior of LCSCs.
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Carcinoma Hepatocelular/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/genética , MicroARNs/biosíntesis , Células Madre Neoplásicas/patología , Antígenos CD/biosíntesis , Cadherinas/biosíntesis , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Proteínas de Homeodominio/biosíntesis , Humanos , Neoplasias Hepáticas/patología , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Células Madre Neoplásicas/metabolismo , Proteínas Represoras/biosíntesis , Vimentina/biosíntesis , Caja Homeótica 2 de Unión a E-Box con Dedos de ZincRESUMEN
OBJECTIVE: To explore whether microRNA-200a (miR-200a) could be used as a novel biomarker of liver cancer using a rat model system. METHODS: Diethylnitrosamine abdominal injection was applied to induce liver cancer in the F344 rat strain (n =40); ten unmodeled rats served as controls. In addition, human subjects with normal healthy liver (n =10), liver cirrhosis (n =10), and liver cancer (n =10) were enrolled in the study. Blood samples from both rats and patients and rats' livers were collected for analysis. Real-time quantitative PCR and enzyme-linked immunosorbent assay were used respectively to measure the expressions of serum miR-200a and alpha-fetoprotein (AFP) for all rat and human subjects. In situ hybridization was used to detect the miR-200a expression in the rats' livers. RESULTS: Comparison of normal rats and the liver cancer modeled rats showed that the latter had significantly lower expression of miR-200a (P less than 0.05), with decreasing expression following the progression of liver injury to cancer (liver cirrhosis rats less than early liver cancer rats less than advanced liver cancer rats); in contrast, the AFP levels were significantly higher in the liver cancer modeled rats only at the early and advanced stages of the liver cancer (P less than 0.05). These RESULTS: suggested that miR-200a expression decreases during the developmental process of liver cancer, while AFP expression increases distinctly at the stage of tumor formation. Analysis of the human subjects' clinical samples showed that miR-200a expression was decreased in both liver cirrhosis patients and liver cancer patients (vs. normal liver subjects, P less than 0.05), while AFP showed abnormal expression only in the patients with liver cancer. Comparison of the normal rats and modeled rats using in situ hybridization showed the positive rates for miR-200a expression were 1.00% +/- 0.01% in rats with normal liver, 0.37% +/- 0.03% in rats with fibrotic liver, 0.14% +/- 0.01% in rats with cirrhotic liver, 0.05% +/- 0.00% in rats with early stage liver cancer, and 0.01% +/- 0.00% in rats with advanced stage liver cancer. CONCLUSION: MiR-200a may play an important role in liver cancer development and may have diagnostic value for indicating early liver cancer.
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Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , MicroARNs/sangre , MicroARNs/metabolismo , Adulto , Anciano , Animales , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Ratas , Ratas Endogámicas F344 , Adulto Joven , alfa-Fetoproteínas/metabolismoRESUMEN
OBJECTIVE: To investigate the early psychological effect of the equilibrium psychological intervention on the person who were injured in the disaster incident. METHODS: The equilibrium psychological intervention was used to the injured person in the Lushan earthquake during the early period. The GHQ-12, HAMA and HAMD were used before and after the evaluation. RESULTS: The score of the GHQ-12 decreased from (3.488 +/- 2.900) to (1.610 +/- 0.840), which showed the significant differences (P < 0.001). The total score of the HAMA and the score of the somatic anxiety factor and mental anxiety factor decreased significantly, compared with the base line (P < 0.001 respectively). The total score of the HAMD and the score of the sretardation factor, somatization factor and sleep disorder factor also decreased significantly, compared with that of the base line (P < 0.005 respectively). CONCLUSION: The equilibrium psychological intervention has the positive effect on the persons who were injured in the disaster incident during the early period.
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Ansiedad/epidemiología , Desastres , Terremotos , Estrés Psicológico/epidemiología , China , HumanosRESUMEN
In halide perovskite solar cells (PSCs), moderate lead iodide (PbI2) can enhance device efficiency by providing some passivation effects, but extremely active PbI2 leads to the current density-voltage hysteresis effect and device instability. In addition, defects distributed on the buried interface of tin oxide (SnO2)/perovskite will lead to the photogenerated carrier recombination. Here, rubidium chloride (RbCl) is introduced at the buried SnO2/perovskite interface, which not only acts as an interfacial passivator to interact with the uncoordinated tin ions (Sn4+) and fill the oxygen vacancy on the SnO2 surface but also converts PbI2 into an inactive (PbI2)2RbCl compound to stabilize the perovskite phase via a bottom-up evolution effect. These synergistic effects deliver a champion PCE of 22.13% with suppressed hysteresis for the W RbCl PSCs, in combination with enhanced environmental and thermal stability. This work demonstrates that the interfacial defect passivation and bottom-up excess PbI2 management using RbCl modifiers are promising strategies to address the outstanding challenges associated with PSCs.
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Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion. Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus. Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells. Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
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Infecciones por Circoviridae , Circovirus , Herpesvirus Suido 1 , Animales , Circovirus/inmunología , Circovirus/genética , Ratones , Herpesvirus Suido 1/inmunología , Herpesvirus Suido 1/genética , Infecciones por Circoviridae/inmunología , Infecciones por Circoviridae/prevención & control , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/genética , Porcinos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Vacunas Sintéticas/inmunología , Seudorrabia/inmunología , Seudorrabia/prevención & control , Femenino , Ratones Endogámicos BALB CRESUMEN
AIM: This study aimed to establish a comprehensive set of recovery-oriented rehabilitation programs for individuals with schizophrenia, comparing the efficacy of video-based rehabilitation to traditional face-to-face interventions. The primary objective was to assess whether video-based rehabilitation could serve as a viable alternative for individuals with schizophrenia residing in remote areas. METHODS: A randomized controlled study was used to recruit 80 patients with schizophrenia in a stable post-hospitalization stage following discharge. Participants were categorized into three groups: 24 in the control group, 21 in the face-to-face group, and 35 in the remote group. Assessment parameters included psychiatric symptoms, social skills, family function and self-stigma. RESULTS: A total of 68 participants completed the program. The findings indicated significant differences (p < .05) between the control group and intervention group, particularly in the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance Scale (PSP). CONCLUSIONS: The rehabilitation program, tailored for patients in the early phase of the schizophrenia spectrum, demonstrates both effectiveness and feasibility in enhancing clinical symptoms and social functions. Notably, interventions conducted via video proved to be equally effective as those administered face-to-face.
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Histone H4 lysine 16 acetylation (H4K16ac), governed by the histone acetyltransferase MOF, orchestrates gene expression regulation and chromatin interaction. However, the roles of MOF and H4K16ac in controlling cellular function and regulating mammalian tissue development remain unclear. Here we show that conditional deletion of Mof in the skin, but not Kansl1, causes severe defects in the self-renewal of basal epithelial progenitors, epidermal differentiation, and hair follicle growth, resulting in barrier defects and perinatal lethality. MOF-regulated genes are highly enriched for essential functions in the mitochondria and cilia. Genetic deletion of Uqcrq, an essential subunit for the electron transport chain (ETC) Complex III, in the skin, recapitulates the defects in epidermal differentiation and hair follicle growth observed in MOF knockout mouse. Together, this study reveals the requirement of MOF-mediated epigenetic mechanism for regulating mitochondrial and ciliary gene expression and underscores the important function of the MOF/ETC axis for mammalian skin development.
Asunto(s)
Histonas , Lisina , Animales , Ratones , Histonas/metabolismo , Lisina/metabolismo , Acetilación , Cromatina/metabolismo , Mitocondrias/metabolismo , Histona Acetiltransferasas/metabolismo , Mamíferos/genéticaRESUMEN
Due to the worldwide ecological and environmental issues induced by heavy metal pollution, including zinc and manganese, the ratio-metric discrimination of Zn2+ and Mn2+ based on CDs is urgently required. In this work, reduced CDs (re-CDs) with the intrinsic dual emissive peaks are obtained, and specific discrimination of Zn2+ and Mn2+ is realized by re-CDs with ratio-metric mode. With the addition of Zn2+, the fluorescent (FL) intensity at 650 nm increases obviously, while that at 680 nm progressively decreases. However, the presence of Mn2+ would induce the quenching of FL intensity at 680 nm while that at 650 nm remains constant. Then the Zn2+ and Mn2+ can be separately determined with the ratio of FL intensity at 650 nm to that at 680 mm (F650/F680). Under optimal conditions, the limit of detection (LOD) of Zn2+ is determined to be 9.09 nmol/L, and that for Mn2+ is estimated to be 0.93 nmol/L, which is much lower than previously reported work and standard level of Zn2+ and Mn2+ permitted in drinking water by WHO. Moreover, the specific recognition of Mn2+ and Zn2+ can be realized via the addition of different masking agents (ethylenediamine for Zn2+ and triethanolamine for Mn2+). Furthermore, our results reveal that the structural changes from -NH-CO to -NC-OH induced by Zn2+ contribute to the shift of FL peak from 680 to 650 nm while both static and dynamic quenching processes are involved in the detection of Mn2+. The ratio-metric probe was successfully applied to Zn2+ and Mn2+ determination in human serum samples and Sandy Lake water.
RESUMEN
The aggregation of SnO2 nanocrystals due to van der Waals interactions is not conducive to the realization of a compact and pinhole-free electron transport layer (ETL). Herein, we have utilized potassium alginate (PA) to self-assemble SnO2 nanocrystals, forming a PA-SnO2 ETL for perovskite solar cells (PSCs). Through density functional theory (DFT) calculations, PA can be effectively absorbed onto the surface of SnO2. This inhibits the agglomeration of SnO2 nanocrystals in solution, forming a smoother pinhole-free film. This also changes the surface contact potential (CPD) of the SnO2 film, which leads to a reduction in the energy barrier between the ETL and the perovskite layers, promotes effective charge transfer, and reduces trap density. Consequently, the power conversion efficiency (PCE) of PSCs with a PA-SnO2 ETL increased from 19.24% to 22.16%, and the short-circuit current (JSC) was enhanced from 23.52 to 25.21 mA cm-2. Furthermore, the PA-modified unpackaged device demonstrates better humidity stability compared to the original device.