RESUMEN
Aphids transmit viruses and are destructive crop pests1. Plants that have been attacked by aphids release volatile compounds to elicit airborne defence (AD) in neighbouring plants2-5. However, the mechanism underlying AD is unclear. Here we reveal that methyl-salicylate (MeSA), salicylic acid-binding protein-2 (SABP2), the transcription factor NAC2 and salicylic acid-carboxylmethyltransferase-1 (SAMT1) form a signalling circuit to mediate AD against aphids and viruses. Airborne MeSA is perceived and converted into salicylic acid by SABP2 in neighbouring plants. Salicylic acid then causes a signal transduction cascade to activate the NAC2-SAMT1 module for MeSA biosynthesis to induce plant anti-aphid immunity and reduce virus transmission. To counteract this, some aphid-transmitted viruses encode helicase-containing proteins to suppress AD by interacting with NAC2 to subcellularly relocalize and destabilize NAC2. As a consequence, plants become less repellent to aphids, and more suitable for aphid survival, infestation and viral transmission. Our findings uncover the mechanistic basis of AD and an aphid-virus co-evolutionary mutualism, demonstrating AD as a potential bioinspired strategy to control aphids and viruses.
Asunto(s)
Aire , Áfidos , Enfermedades de las Plantas , Plantas , Ácido Salicílico , Transducción de Señal , Áfidos/fisiología , Áfidos/virología , Interacciones Microbiota-Huesped , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/virología , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Plantas/parasitología , Plantas/virología , Ácido Salicílico/metabolismo , Simbiosis , Nicotiana/inmunología , Nicotiana/metabolismo , Nicotiana/parasitología , Nicotiana/virología , Proteínas Virales/metabolismo , AnimalesRESUMEN
Wing dimorphism of insect vectors is a determining factor for viral long-distance dispersal and large-area epidemics. Although plant viruses affect the wing plasticity of insect vectors, the potential underlying molecular mechanisms have seldom been investigated. Here, we found that a planthopper-vectored rice virus, rice stripe virus (RSV), specifically induces a long-winged morph in male insects. The analysis of field populations demonstrated that the long-winged ratios of male insects are closely associated with RSV infection regardless of viral titers. A planthopper-specific and testis-highly expressed gene, Encounter, was fortuitously found to play a key role in the RSV-induced long-winged morph. Encounter resembles malate dehydrogenase in the sequence, but it does not have corresponding enzymatic activity. Encounter is upregulated to affect male wing dimorphism at early larval stages. Encounter is closely connected with the insulin/insulin-like growth factor signaling pathway as a downstream factor of Akt, of which the transcriptional level is activated in response to RSV infection, resulting in the elevated expression of Encounter. In addition, an RSV-derived small interfering RNA directly targets Encounter to enhance its expression. Our study reveals an unreported mechanism underlying the direct regulation by a plant virus of wing dimorphism in its insect vectors, providing the potential way for interrupting viral dispersal.
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Epidemias , Virus de Plantas , Infecciones por Virus Sincitial Respiratorio , Tenuivirus , Masculino , Animales , Virus de Plantas/genética , Tenuivirus/genética , Insectos Vectores , Péptidos Similares a la InsulinaRESUMEN
Identifying genotype-by-environment interaction (GEI) is challenging because the GEI analysis generally has low power. Large-scale consortium-based studies are ultimately needed to achieve adequate power for identifying GEI. We introduce Multi-Trait Analysis of Gene-Environment Interactions (MTAGEI), a powerful, robust, and computationally efficient framework to test gene-environment interactions on multiple traits in large data sets, such as the UK Biobank (UKB). To facilitate the meta-analysis of GEI studies in a consortium, MTAGEI efficiently generates summary statistics of genetic associations for multiple traits under different environmental conditions and integrates the summary statistics for GEI analysis. MTAGEI enhances the power of GEI analysis by aggregating GEI signals across multiple traits and variants that would otherwise be difficult to detect individually. MTAGEI achieves robustness by combining complementary tests under a wide spectrum of genetic architectures. We demonstrate the advantages of MTAGEI over existing single-trait-based GEI tests through extensive simulation studies and the analysis of the whole exome sequencing data from the UKB.
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Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Humanos , Fenotipo , Simulación por ComputadorRESUMEN
Genotype-by-environment interaction (GEI or GxE) plays an important role in understanding complex human traits. However, it is usually challenging to detect GEI signals efficiently and accurately while adjusting for population stratification and sample relatedness in large-scale genome-wide association studies (GWAS). Here we propose a fast and powerful linear mixed model-based approach, fastGWA-GE, to test for GEI effect and G + GxE joint effect. Our extensive simulations show that fastGWA-GE outperforms other existing GEI test methods by controlling genomic inflation better, providing larger power and running hundreds to thousands of times faster. We performed a fastGWA-GE analysis of ~7.27 million variants on 452 249 individuals of European ancestry for 13 quantitative traits and five environment variables in the UK Biobank GWAS data and identified 96 significant signals (72 variants across 57 loci) with GEI test P-values < 1 × 10-9, including 27 novel GEI associations, which highlights the effectiveness of fastGWA-GE in GEI signal discovery in large-scale GWAS.
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Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Humanos , Fenotipo , Genotipo , Modelos Lineales , Polimorfismo de Nucleótido SimpleRESUMEN
Exosomes play a key role in virus exocytosis and transmission. The exportin family is usually responsible for cargo nucleocytoplasmic trafficking, and they are frequently found in exosomes. However, the function of exportins sorted in exosomes remains unknown. Here, we successfully isolated "cup holder"-like exosomes from the saliva of â¼30,000 small brown planthoppers, which are vectors of rice stripe virus (RSV). RSV virions were packed in comparatively large exosomes. Four viral genomic RNAs at a certain ratio were identified in the saliva exosomes. The virions contained in the saliva exosomes were capable of replicating and causing disease in rice plants. Interference with each phase of the insect exosome system affected the transmission of RSV from the insect vectors to rice plants. Fragmented exportin 6 was coimmunoprecipitated with viral nucleocapsid protein in saliva and sorted to exosomes via interactions with the cargo sorting protein VPS37a. When the expression of exportin 6 was knocked down, the amounts of RSV secreted in saliva and rice plants were reduced by 60% and 74%, respectively. These results showed that exportin 6 acted as a vehicle for transporting RSV into exosomes to overcome the barrier of insect salivary glands for horizontal transmission. Exportin 6 would represent an ideal target that could be manipulated to control the outbreak of insect-borne viruses in the future.
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Exosomas , Hemípteros , Carioferinas , Oryza , Tenuivirus , Animales , Exosomas/virología , Hemípteros/virología , Insectos Vectores/virología , Carioferinas/metabolismo , Oryza/virología , Enfermedades de las Plantas/virología , Tenuivirus/patogenicidadRESUMEN
BACKGROUND: HER3 (ErbB3), a member of the human epidermal growth factor receptor family, is frequently overexpressed in various cancers. Multiple HER3-targeting antibodies and antibody-drug conjugates (ADCs) were developed for the solid tumor treatment, however none of HER3-targeting agent has been approved for tumor therapy yet. We developed DB-1310, a HER3 ADC composed of a novel humanized anti-HER3 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor payload (P1021), and evaluate the efficacy and safety of DB-1310 in preclinical models. METHODS: The binding of DB-1310 to Her3 and other HER families were measured by ELISA and SPR. The competition of binding epitope for DB-1310 and patritumab was tested by FACS. The sensitivity of breast, lung, prostate and colon cancer cell lines to DB-1310 was evaluated by in vitro cell killing assay. In vivo growth inhibition study evaluated the sensitivity of DB-1310 to Her3 + breast, lung, colon and prostate cancer xenograft models. The safety profile was also measured in cynomolgus monkey. RESULTS: DB-1310 binds HER3 via a novel epitope with high affinity and internalization capacity. In vitro, DB-1310 exhibited cytotoxicity in numerous HER3 + breast, lung, prostate and colon cancer cell lines. In vivo studies in HER3 + HCC1569 breast cancer, NCI-H441 lung cancer and Colo205 colon cancer xenograft models showed DB-1310 to have dose-dependent tumoricidal activity. Tumor suppression was also observed in HER3 + non-small cell lung cancer (NSCLC) and prostate cancer patient-derived xenograft (PDX) models. Moreover, DB-1310 showed stronger tumor growth-inhibitory activity than patritumab deruxtecan (HER3-DXd), which is another HER3 ADC in clinical development at the same dose. The tumor-suppressive activity of DB-1310 synergized with that of EGFR tyrosine kinase inhibitor, osimertinib, and exerted efficacy also in osimertinib-resistant PDX model. The preclinical assessment of safety in cynomolgus monkeys further revealed DB-1310 to have a good safety profile with a highest non severely toxic dose (HNSTD) of 45 mg/kg. CONCLUSIONS: These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.
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Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias del Colon , Inmunoconjugados , Indoles , Neoplasias Pulmonares , Neoplasias de la Próstata , Pirimidinas , Inhibidores de Topoisomerasa I , Animales , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular , Epítopos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Macaca fascicularis/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Receptor ErbB-3 , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hypertension is a leading risk factor for disease burden worldwide. Vascular contraction and remodeling contribute to the development of hypertension. Glutathione S-transferase P1 (Gstp1) plays several critical roles in both normal and neoplastic cells. In this study, we investigated the effect of Gstp1 on hypertension as well as on vascular smooth muscle cell (VSMC) contraction and phenotypic switching. We identified the higher level of Gstp1 in arteries and VSMCs from hypertensive rats compared with normotensive rats for the first time. We then developed Adeno-associated virus 9 (AAV9) mediated Gstp1 down-regulation and overexpression in rats and measured rat blood pressure by using the tail-cuff and the carotid catheter method. We found that the blood pressure of spontaneously hypertensive rats (SHR) rose significantly with Gstp1 down-regulation and reduced apparently after Gstp1 overexpression. Similar results were obtained from the observations of 2-kidney-1-clip renovascular (2K1C) hypertensive rats. Gstp1 did not influence blood pressure of normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Further in vitro study indicated that Gstp1 knockdown in SHR-VSMCs promoted cell proliferation, migration, dedifferentiation and contraction, while Gstp1 overexpression showed opposite effects. Results from bioinformatic analysis showed that the Apelin/APLNR system was involved in the effect of Gstp1 on SHR-VSMCs. The rise in blood pressure of SHR induced by Gstp1 knockdown could be reversed by APLNR antagonist F13A. We further found that Gstp1 enhanced the association between APLNR and Nedd4 E3 ubiquitin ligases to induce APLNR ubiquitination degradation. Thus, in the present study, we discovered a novel anti-hypertensive role of Gstp1 in hypertensive rats and provided the experimental basis for designing an effective anti-hypertensive therapeutic strategy.
Asunto(s)
Presión Sanguínea , Gutatión-S-Transferasa pi , Hipertensión , Músculo Liso Vascular , Ubiquitina-Proteína Ligasas Nedd4 , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Ubiquitinación , Animales , Masculino , Ratas , Proliferación Celular , Gutatión-S-Transferasa pi/metabolismo , Gutatión-S-Transferasa pi/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/genéticaRESUMEN
T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Adolescente , Adulto , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Adulto Joven , Pronóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Tasa de Supervivencia , Estudios Retrospectivos , Trasplante Homólogo , Leucemia-Linfoma de Células T del Adulto/terapia , Leucemia-Linfoma de Células T del Adulto/mortalidad , Resultado del Tratamiento , Aloinjertos , Estudios de CohortesRESUMEN
The potential treatment option of targeting DNA methyltransferase 1 (DNMT1) has been explored, but further investigation is required to assess the efficacy of combination therapy in acute myeloid leukemia (AML). In this study, bioinformatics and online databases were utilized to select the combined therapeutic targets. The potential kinases associated with DNMT1-related genes in AML were analyzed using the Cancer Genome Atlas (TCGA) database and X2K Appyter (Expression2Kinases) database. In-vitro evaluations were conducted to assess the synergistic effects between DNMT1 and ATR/ATM in five AML cell lines (MOLM-16, NB-4, HEL 92.1.7, HEL, EOL-1). In our study, ATR and ATM are primarily the kinases associated with DNMT1-related genes in AML. We observed a significant upregulation of DNMT1, ATR, and ATM expression in AML tissues and cell lines. The five AML cell lines demonstrated sensitivity to monotherapy with GSK-368, AZD-1390, or AZD-6738 (EC50 value ranges from 5.461 to 7.349 nM, 5.821 to 10.120 nM, and 7.618 to 10.100 nM, respectively). A considerable synergistic effect was observed in AML cell lines when combining GSK-368 and AZD-1390, GSK-368 and AZD-6738, or AZD-1390 and AZD-6738, resulting in induced cell apoptosis and inhibited cell growth. DNMT1, ATM, and ATR possess potential as therapeutic targets for AML. Both individual targeting and combination targeting of these molecules have been confirmed as promising therapeutic approaches for AML.
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Indoles , Leucemia Mieloide Aguda , Pirimidinas , Sulfonamidas , Humanos , Línea Celular Tumoral , Pirimidinas/farmacología , Morfolinas/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Apoptosis , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismoRESUMEN
Streaming data routinely generated by social networks, mobile or web applications, e-commerce, and electronic health records present new opportunities to monitor the impact of an intervention on an outcome via causal inference methods. However, most existing causal inference methods have been focused on and applied to static data, that is, a fixed data set in which observations are pooled and stored before performing statistical analysis. There is thus a pressing need to turn static causal inference into online causal learning to support near real-time monitoring of treatment effects. In this paper, we present a framework for online estimation and inference of treatment effects that can incorporate new information as it becomes available without revisiting prior observations. We show that, under mild regularity conditions, the proposed online estimator is asymptotically equivalent to the offline oracle estimator obtained by pooling all data. Our proposal is motivated by the need for near real-time vaccine effectiveness and safety monitoring, and our proposed method is applied to a case study on COVID-19 vaccine safety surveillance.
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Vacunas contra la COVID-19 , COVID-19 , Vigilancia de Productos Comercializados , Humanos , Vigilancia de Productos Comercializados/estadística & datos numéricos , Vigilancia de Productos Comercializados/métodos , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Causalidad , Modelos Estadísticos , SARS-CoV-2 , Simulación por ComputadorRESUMEN
Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.
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Estructuras Metalorgánicas , Especies Reactivas de Oxígeno , Estructuras Metalorgánicas/química , Especies Reactivas de Oxígeno/metabolismo , Humanos , Depuradores de Radicales Libres/química , Nanoestructuras/química , Catalasa/química , Catalasa/metabolismo , Animales , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/químicaRESUMEN
AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.
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Cadmio , Plomo , Encuestas Nutricionales , Periodontitis , Humanos , Periodontitis/sangre , Periodontitis/epidemiología , Masculino , Femenino , Cadmio/sangre , Cadmio/orina , Plomo/sangre , Adulto , Persona de Mediana Edad , Teorema de Bayes , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Metales/sangre , Metales/orina , Anciano , Modelos Logísticos , Estradiol/sangre , Estudios TransversalesRESUMEN
Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer's disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Pruebas Neuropsicológicas , Disfunción Cognitiva/patología , Encéfalo , Sustancia Gris/patología , Enfermedad de Alzheimer/patología , Imagen por Resonancia Magnética , Atrofia/patología , Diagnóstico PrecozRESUMEN
BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.
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Cardiotoxicidad , Doxorrubicina , Exosomas , Momordica charantia , Factor 2 Relacionado con NF-E2 , Animales , Cardiotoxicidad/prevención & control , Cardiotoxicidad/metabolismo , Momordica charantia/química , Exosomas/metabolismo , Ratas , Factor 2 Relacionado con NF-E2/metabolismo , Línea Celular , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Supervivencia Celular/efectos de los fármacos , Ratas Sprague-Dawley , Proteína Sequestosoma-1/metabolismoRESUMEN
AIM: The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. METHODS: We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. RESULTS: A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). CONCLUSION: There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.
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Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugíaRESUMEN
In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription factor (TF) is required for specifying the sepals and petals identities and confers a major A-function to antagonize the C-function in the outer floral whorls. In the asterid species Petunia, the AP2-type ROB TFs are required for perianth and pistil development, as well as repressing the B-function together with TOE-type TF BEN. In Long-homostyle (LH) Fagopyrum esculentum, VIGS-silencing showed that FaesAP2 is mainly involved in controlling filament and style length, but FaesTOE is mainly involved in regulating filament length and pollen grain development. Both FaesAP2 (AP2-type) and FaesTOE (TOE-type) are redundantly involved in style and/or filament length determination instead of perianth development. However, neither FaesAP2 nor FaesTOE could directly repress the B and/or C class genes in common buckwheat. Moreover, the FaesAP1_2 silenced flower showed tepal numbers, and filament length decreased obviously. Interestingly, yeast one-hybrid (Y1H) and dual-luciferase reporter (DR) further suggested that FaesTOE directly up-regulates FaesAP1_2 to be involved in filament length determination in LH common buckwheat. Moreover, the knockdown of FaesTOE expression could result in expression down-regulation of the directly target FaesAP1_2 in the FaesTOE-silenced LH plants. Our findings uncover a stamen development pathway in common buckwheat and offer deeper insight into the functional evolution of AP2 orthologs in the early-diverging core eudicots.
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Fagopyrum , Flores , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Fagopyrum/genética , Fagopyrum/crecimiento & desarrollo , Fagopyrum/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Given that the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (BC) is crucial during the BC progression, the mechanism involved in the invasion transition behind triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER-positive) subtype has remained elusive. This article detected distinct invasion patterns of BC cells between the ER-positive and TNBC using intraductal murine models with intraductal administration of carbon nanoparticles (CNPs). First, the feasibility of the utility of CNPs as a tracer was proved. The area ratio of CNPs and tumor cells invading the stroma at the late stage was found significantly higher than that in the early stage in MNU-induced ER-positive BC. However, opposite results were obtained in the triple-negative model. Consequently, we proposed that the ER-positive phenotype cells behave differently between different stages during tumor progression while there is no such difference in the invasion process of TNBC cells. The analysis regarding the duct integrity along with immunohistochemical characteristics further explained the distinct invasion features between the ER-positive and triple-negative subtypes. Last, the relationship between the duct thickness and the duct integrity suggested that ER-positive tumors gradually increased in size within the lumen before the invasion. Overall, this study suggested the different invasion characteristics of ER-positive BC and TNBC in vivo.
Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Femenino , Receptores de Estrógenos , Receptor ErbB-2/análisis , Carcinoma Intraductal no Infiltrante/patología , Carbono , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Biomarcadores de TumorRESUMEN
In this paper, we propose a weak measurement method using two pointers to estimate the magneto-optical Kerr angle, which is robust to ellipticity. The double pointers are the amplified displacement shift and intensity of the post-selected light beam, which are the conventional information carried by the light beam and can be directly output by a detector (such as a charge-coupled device). We demonstrate that the product of the double pointers is only related to the phase variation between two basic vectors and independent of the amplitude errors. In the measurement process, when there is an amplitude change or additional amplitude noise between two eigenstates, the product of two pointers is very useful in extracting phase information and shielding amplitude noise. In addition, the product of two pointers has a good linear relationship with the phase variation and a larger dynamic measurement range. This method is applied to measure the magneto-optical Kerr angle of NiFe film. The Kerr angle can be directly obtained using the product of the light intensity and the amplified displacement shift. This scheme is of great significance for the measurement of the Kerr angle of magnetic films.
RESUMEN
In this paper, we use weak measurement to study the mixed magneto-optical Kerr effects (MOKEs) in a magnetic single layer of Co and in organic/Co bilayer films. The relationship between the amplified shift and the MOKE parameters is theoretically established and then experimentally observed as a function of both the magnetization intensity and the magnetization direction in magnetic thin films with an arbitrary magnetization. Furthermore, we experimentally observe a magnetic coupling at the organic/ferromagnetic interface. Due to this being a robust coupling, there is a significant dependence of the amplified shift with the thickness of the organic layer. This work has value for its application in the magnetic measurement technique for the more general case based on weak measurement.
RESUMEN
A versatile system combining surface plasmon resonance (SPR) and weak value amplification (WVA) is presented, which can measure the optical activity and refractive index of chiral/achiral molecules, ionic compounds, and their mixture in solution individually or simultaneously. The variations in output light intensity directly exhibit high sensitivity to changes in optical activity and refractive index of the aforementioned substances. Furthermore, by examining the correlation between the intensity variation trend and the optical activity of the chiral molecule, the molecule's absolute configuration can be ascertained. Utilizing this instrument, optical rotation with a resolution of 3.04 × 10-6â rad and refractive index with a resolution of 5.57 × 10-9 RIU were obtained. As an attempt at practical application, this sensor was used to detect the adulteration of glucose and fructose in pure honey. Not only can such compromised honey be distinguished from pure honey using the refractive index or optical rotation, but the difference in optical activity can also be employed to effectively differentiate between adulterated honey samples containing glucose and fructose separately.