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Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.
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Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acidfunctionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.
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Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Neoplasias , Platino (Metal) , Estilbenos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Camptotecina/administración & dosificación , Camptotecina/farmacología , Liberación de Fármacos , Sinergismo Farmacológico , Ácido Fólico/química , Humanos , Ratones , Nanopartículas , Neoplasias/tratamiento farmacológico , Platino (Metal)/química , Polímeros/uso terapéutico , Estilbenos/administración & dosificación , Estilbenos/farmacología , Microambiente TumoralRESUMEN
Metastasis contributes to the dismal prognosis of bladder cancer (BLCA). The mechanical status of the cell membrane is expected to mirror the ability of cell migration to promote cancer metastasis. However, the mechanical characteristics and underlying molecular profile associated with BLCA metastasis remain obscure. To study the unique cellular architecture and traits associated with cell migration, using a process called cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) we generated an aptamer-based molecular probe, termed spl3c, which identified cytoskeleton-associated protein 4 (CKAP4). CKAP4 was associated with tumor metastasis in BLCA, but we also found it to be a mechanical regulator of BLCA cells through the maintenance of a central-to-peripheral gradient of stiffness on the cell membrane. Notably, such mechanical traits were transportable through exosome-mediated intercellular CKAP4 trafficking, leading to significant enhancement of migration in recipient cells and, consequently, aggravating metastatic potential in vivo. Taken together, our study shows the robustness of this aptamer-based molecular tool for biomarker discovery, revealing the dominance of a CKAP4-induced central-to-peripheral gradient of membrane stiffness that benefits cell migration and delineating the role of exosomes in mediating mechanical signaling in BLCA metastasis.
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Exosomas , Mecanotransducción Celular , Proteínas de la Membrana , Neoplasias de la Vejiga Urinaria , Línea Celular Tumoral , Movimiento Celular , Exosomas/metabolismo , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Pronóstico , Técnica SELEX de Producción de Aptámeros , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Aberrant phosphorylation of receptor tyrosine kinases (RTKs) is usually involved in tumor initiation, progression, and metastasis. However, developing specific and efficient molecular tools to regulate RTK phosphorylation remains a considerable challenge. In this study, we reported novel aptamer-based chimeras to inhibit the phosphorylation of RTKs, such as c-Met and EGFR, by enforced recruitment of a protein tyrosine phosphatase receptor type F (PTPRF). Our studies revealed that aptamer-based chimeras displayed a generic and potent inhibitory effect on RTK phosphorylation induced by growth factor or auto-dimerization in different cell lines and modulated cell biological behaviors by recruiting PTPRF. Furthermore, based on angstrom accuracy of the DNA duplex, the maximum catalytic radius of PTPRF was determined as â¼25.84 nm, providing a basis for the development of phosphatase-recruiting strategies. Taken together, our study provides a generic methodology not only for selectively mediating RTK phosphorylation and cellular biological processes but also for developing novel therapeutic drugs.
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Aptámeros de Nucleótidos , Transducción de Señal , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Humanos , Transducción de Señal/efectos de los fármacos , Fosforilación , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/químicaRESUMEN
Chimeric antigen receptor (CAR)-modified T cell therapy has achieved remarkable efficacy in treating hematological malignancies, but it confronts many challenges in treating solid tumors, such as the immunosuppressive microenvironment of the solid tumors. These factors reduce the antitumor activity of CAR-T cells in clinical trials. Therefore, we used the immunocytokine interleukin-12 (IL-12) to enhance the efficacy of CAR-T cell therapy. In this study, we engineered CAR-IL12R54 T cells that targeted mesothelin (MSLN) and secreted a single-chain IL-12 fused to a scFv fragment R54 that recognized a different epitope on mesothelin. The evaluation of the anti-tumor activity of the CAR-IL12R54 T cells alone or in combination with anti-PD-1 antibody in vitro and in vivo was followed by the exploration of the functional mechanism by which the immunocytokine IL-12 enhanced the antitumor activity. CAR-IL12R54 T cells had potency to lyse mesothelin positive tumor cells in vitro. In vivo studies demonstrated that CAR-IL12R54 T cells were effective in controlling the growth of established tumors in a xenograft mouse model with fewer side effects than CAR-T cells that secreted naked IL-12. Furthermore, combination of PD-1 blockade antibody with CAR-IL12R54 T cells elicited durable anti-tumor responses. Mechanistic studies showed that IL12R54 enhanced Interferon-γ (IFN-γ) production and dampened the activity of regulatory T cells (Tregs). IL12R54 also upregulated CXCR6 expression in the T cells through the NF-κB pathway, which facilitated T cell infiltration and persistence in the tumor tissues. In summary, the studies provide a good therapeutic option for the clinical treatment of solid tumors.
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Inmunoterapia Adoptiva , Interleucina-12 , Mesotelina , Receptores Quiméricos de Antígenos , Animales , Interleucina-12/inmunología , Interleucina-12/genética , Humanos , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Línea Celular Tumoral , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/antagonistas & inhibidores , Microambiente Tumoral/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/inmunología , Linfocitos T/inmunologíaRESUMEN
Aptamers' vast conformation ensemble consisting of interconverting substates severely impairs their performance and applications in biomedicine. Therefore, developing new chemistries stabilizing aptamer conformation and exploring the conformation-performance relationship are highly desired. Herein, we developed an 8-methoxypsoralen-based photochemically covalent lock to stabilize aptamer conformation via crosslinking the inter-stranded thymine nucleotides at TpA sites. Systematical studies and molecular dynamics simulations were performed to explore the conformation-performance relationship of aptamers, revealing that conformation-stabilized aptamers displayed better ability to bind targets, adapt to physiological environment, resist macrophage uptake, prolong circulation half-life, accumulate in and penetrate into tumor than their counterparts. As expected, conformation-stabilized aptamers efficiently improved the therapeutic efficacy of aptamer-drug conjugation on tumor-bearing mice. Collectively, our study has developed a general, simple and economic strategy to stabilize aptamer conformation and shed light on the conformation-performance relationship of aptamers, laying a basis for promoting their basic researches and applications in biomedicine.
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Aptámeros de Nucleótidos , Ratones , Animales , Aptámeros de Nucleótidos/química , Conformación Molecular , Simulación de Dinámica Molecular , Técnica SELEX de Producción de AptámerosRESUMEN
BACKGROUND: Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years. METHODS: In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT-PCR. RESULTS: Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling. CONCLUSION: Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone-based therapeutic strategies.
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Glioma , Transducción de Señal , Animales , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Glioma/genética , Quinasas Asociadas a rho/metabolismo , Temozolomida/farmacología , Temozolomida/uso terapéutico , Cumarinas/farmacología , Cumarinas/uso terapéuticoRESUMEN
Efficient and thorough treatment of dye wastewater is essential to achieve ecological harmony. In this study, a new type of calcium-based modified coal gangue (Ca-CG) was prepared by using solid waste coal gangue as raw material and a CaCl2 modifier, which was used for the removal of malachite green, methylene blue, crystal violet, methyl violet and other dyes in water. When the dosage of Ca-CG was 1-5 g/L, the dosage of Ca-CG was the main factor affecting the dye adsorption effect. The adsorption effects of Ca-CG on four dyes were as follows: malachite green > crystal violet > methylene blue > methyl violet. Kinetics, isotherms and thermodynamic analysis showed that the adsorption of malachite green, methyl blue, crystal violet and methyl violet by Ca-CG fitted the second-order kinetic model, and adsorption with chemical reaction is the main process. The adsorption of four dyes by Ca-CG conformed to the Freundlich model, which is dominated by multi-molecular layer adsorption, and the adsorption was easy to carry out. The adsorption process of Ca-CG on the four dyes was spontaneous. The results of FTIR, XRD and SEM showed that the calcium-based materials such as lipscombite and dolomite were the key to the adsorption of malachite green by Ca-CG, and the main mechanisms for the adsorption of malachite green by Ca-CG are surface precipitation, electrostatic action, and chelation reaction. Ca-CG adsorption has great potential for the removal of dye wastewater.
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Traumatic brain injury (TBI) can negatively impact systemic organs, which can lead to more death and disability. However, the mechanism underlying the effect of TBI on systemic organs remains unclear. In previous work, we found that brain-derived extracellular vesicles (BDEVs) released from the injured brain can induce systemic coagulation with a widespread fibrin deposition in the microvasculature of the lungs, kidney, and heart in a mouse model of TBI. In this study, we investigated whether BDEVs can induce heart, lung, liver, and kidney injury in TBI mice. The results of pathological staining and related biomarkers indicated that BDEVs can induce histological damage and systematic dysfunction. In vivo imaging system demonstrated that BDEVs can gather in systemic organs. We also found that BDEVs could induce cell apoptosis in the lung, liver, heart, and kidney. Furthermore, we discovered that BDEVs could cause multi-organ endothelial cell damage. Finally, this secondary multi-organ damage could be relieved by removing circulating BDEVs. Our research provides a novel perspective and potential mechanism of TBI-associated multi-organ damage.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Vesículas Extracelulares , Ratones , Animales , Encéfalo/patología , Lesiones Encefálicas/patología , Apoptosis , Vesículas Extracelulares/patologíaRESUMEN
BACKGROUND: Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. METHODS: We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. RESULTS: Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. CONCLUSIONS: In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.
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Conmoción Encefálica , Disfunción Cognitiva , Enfermedades Neurodegenerativas , Ratones , Animales , Conmoción Encefálica/complicaciones , Conmoción Encefálica/tratamiento farmacológico , Conmoción Encefálica/psicología , Modelos Animales de Enfermedad , Disfunción Cognitiva/tratamiento farmacológico , Inmunoglobulina G , EncéfaloRESUMEN
Severe traumatic brain injury (TBI) often causes an acute systemic hypercoagulable state that rapidly develops into consumptive coagulopathy. We have recently demonstrated that TBI-induced coagulopathy (TBI-IC) is initiated and disseminated by brain-derived extracellular vesicles (BDEVs) and propagated by extracellular vesicles (EVs) from endothelial cells and platelets. Here, we present results from a study designed to test the hypothesis that anticoagulation targeting anionic phospholipid-expressing EVs prevents TBI-IC and improves the outcomes of mice subjected to severe TBI. We evaluated the effects of a fusion protein (ANV-6L15) for improving the outcomes of TBI in mouse models combined with in vitro experiments. ANV-6L15 combines the phosphatidylserine (PS)-binding annexin V (ANV) with a peptide anticoagulant modified to preferentially target extrinsic coagulation. We found that ANV-6L15 reduced intracranial hematoma by 70.2%, improved neurological function, and reduced death by 56.8% in mice subjected to fluid percussion injury at 1.9 atm. It protected the TBI mice by preventing vascular leakage, tissue edema, and the TBI-induced hypercoagulable state. We further showed that the extrinsic tenase complex was formed on the surfaces of circulating EVs, with the highest level found on BDEVs. The phospholipidomic analysis detected the highest levels of PS on BDEVs, as compared with EVs from endothelial cells and platelets (79.1, 15.2, and 3.5 nM/mg of protein, respectively). These findings demonstrate that TBI-IC results from a trauma-induced hypercoagulable state and may be treated by anticoagulation targeting on the anionic phospholipid-expressing membrane of EVs from the brain and other cells.
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Anexina A5/uso terapéutico , Anticoagulantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Vesículas Extracelulares/efectos de los fármacos , Fosfolípidos/metabolismo , Proteínas Recombinantes de Fusión/uso terapéutico , Trombofilia/tratamiento farmacológico , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patología , Masculino , Ratones Endogámicos C57BL , Trombofilia/etiología , Trombofilia/metabolismo , Trombofilia/patologíaRESUMEN
PURPOSE: Clinical outcome of spinal cavernous malformation (SCM) varies because of its unclear natural history, and reliable prognostic prediction model for SCM patients is limited. The aim of the present study was to investigate potential factors that predict one-year neurological status in postoperative patients with SCM. METHODS: This was a multicenter prospective observational study in consecutive patients with SCMs. SCMs treated microsurgically between January 2015 and January 2021 were included. Outcome was defined as the American Spinal Injury Association Impairment Scale (AIS) grade at one year after operation. Multivariable analyses were used to construct the best predictive model for patient outcomes. RESULTS: We identified 268 eligible SCM patients. Neurological outcome had worsened from preoperative baseline in 51 patients (19.0%) at one year. In the multivariable logistic regression, the best predictive model for unfavorable outcome included symptom duration ≥ 26 months (95% CI 2.80-16.96, P < 0.001), size ≤ 5 mm (95% CI 1.43-13.50, P = 0.010), complete intramedullary (95% CI 1.69-8.14, P = 0.001), subarachnoid hemorrhage (95% CI 2.92-12.57, P < 0.001), AIS B (95% CI 1.91-40.93, P = 0.005) and AIS C (95% CI 1.12-14.54, P = 0.033). CONCLUSIONS: Admission size of the lesion, morphology, symptom duration, AIS grade and the presence of subarachnoid hemorrhage were strong outcome predictors regarding prognostication of neurological outcome in postoperative patients with SCMs. A decision to surgically remove a symptomatic SCM should be justified by systematic analysis of all factors potentially affecting outcome.
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Anomalías Musculoesqueléticas , Hemorragia Subaracnoidea , Humanos , Estudios Prospectivos , Procedimientos Neuroquirúrgicos , Pronóstico , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
This paper describes the design of a low-noise, high-speed readout-integrated circuit for use in InGaAs infrared focal plane arrays, and analyzes the working principle and noise index of the pixel circuit in detail. The design fully considers the dynamic range, noise, and power consumption of the pixel circuit in which a capacitance transimpedance amplifier structure is adopted as the input stage circuit, and chip fabrication via an XFAB 0.18 µm CMOS process is successfully realized. The ROIC adopts monolithic integration and implements various functions, such as windowing, subsampling, and different integration and readout modes. The ROIC reached an array scale of 32 × 32, a frame rate of 100 Hz, and a readout rate of 20 Mbps with an analog power consumption of less than 52 mW. The measurement results show that the input reference noise can be reduced to 143 e- via the CDS, and the fully customized scheme has certain advantages in the research of high-performance ROICs.
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TiO2 has attracted significant research interest, principally due to its nontoxicity, high stability, and abundance. Carbon-doped TiO2 can improve light absorption efficiency. In order to prepare high-efficiency photocatalysts, carbon-doped composites were prepared by hydrothermal reaction in a high-pressure reactor, and then TiO2/CNT mesoporous composites were prepared by the sol-gel method in an ultrasonic environment. Characterized by SEM and TEM, the composite materials contained TiO2 nanoparticles as well as CNT. After phase analysis, it was the anatase-doped phase. The following infrared light absorption performance and Escherichia coli bactericidal performance tests showed that it had better infrared and visible light absorption performance than pure TiO2. The TiO2/CNT mesoporous nanomaterials synthesized in this work are possible for clean industrial productions.
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The feasibility of decomplexation removal of typical contaminants in electroplating wastewater, complexed Cu(II) with 1-hydroxyethylidene-1,1-diphosphonic acid (Cu-HEDP), was first performed by a three-dimensional electrode reactor with activated biochar as particle electrodes. For the case of 50 mg/L Cu-HEDP, Cu(II) removal (90.7%) and PO43- conversion (34.9%) were achieved under the conditions of electric current 40 mA, initial pH 7, acid-treated almond shell biochar (AASB) addition 20 g/L, and reaction time 180 min, with second-order rate constants of 1.10 × 10-3 and 1.94 × 10-5 min-1 respectively. The growing chelating effect between Cu(II) and HEDP and the comprehensive actions of adsorptive accumulation, direct and indirect oxidation given by particle electrodes accounted for the enhanced removal of Cu-HEDP, even though the mineralization of HEDP was mainly dependent on anode oxidation. The performance attenuation of AASB particle electrodes was ascribed to the excessive consumption of oxygen-containing functionalities during the reaction, especially acidic carboxylic groups and quinones on particle electrodes, which decreased from 446.74 to 291.48 µmol/g, and 377.55 to 247.71 µmol/g, respectively. Based on the determination of adsorption behavior and indirect electrochemical oxidation mediated by in situ electrogenerated H2O2 and reactive oxygen species (e.g., â¢OH), a possible removal mechanism of Cu-HEDP by three-dimensional electrolysis was further proposed.
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Aguas Residuales , Contaminantes Químicos del Agua , Carbón Orgánico , Electrodos , Electrólisis/métodos , Ácido Etidrónico , Peróxido de Hidrógeno , Oxidación-Reducción , Oxígeno , Quinonas , Especies Reactivas de OxígenoRESUMEN
Current action mechanisms for aptamer-based therapeutics depend on occupancy-driven pharmacology to mediate protein functions. We report a new mechanism where aptamers leverage cellular proteasomal degradation system to degrade proteins for cancer treatment. A DNA aptamer (hereinafter referred to as c-Met-Ap) binds to the extracellular domain of mesenchymal-epithelial transition factor (c-Met) and selectively induces c-Met phosphorylation at Y1003 and Y1349. The phosphorylation of Y1003 recruits E3 ubiquitin ligase casitas B-lineage lymphoma, causing c-Met ubiquitination and degradation in the proteasome. Furthermore, c-Met-Ap can induce a decrease in the heterodimeric partner proteins of c-Met and the downstream effector proteins in the c-Met signal axis, effectively inhibiting tumor growth in A549 tumor-bearing BALB/c mice. Our study uncovers a novel, actionable mechanism for aptamer therapeutics and opens a new avenue for developing highly efficient anticancer drugs.
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Complejo de la Endopetidasa Proteasomal , Ubiquitina-Proteína Ligasas , Ratones , Animales , Complejo de la Endopetidasa Proteasomal/metabolismo , Citoplasma/metabolismo , Ubiquitinación , Ubiquitina-Proteína Ligasas/metabolismo , FosforilaciónRESUMEN
BACKGROUND: Chinese chestnut is an economically important tree species whose yield and quality are seriously affected by red spider attack. Tannins is one of the most important class secondary metabolites in plants, and is closely associated with plant defense mechanisms against insect and herbivory. In our previous studies, it was revealed that several low-tannin foxtail millet varieties growing under the Chinese chestnut trees could attract red spiders to feed on their leaves and protect the chestnut trees from the infestation of red spiders, meanwhile, the growth and yield of foxtail millet plants themselves were not greatly affected. RESULTS: To identify genes related to leaf tannin content and selection of foxtail millet germplasm resources with low tannin content for interplanting with Chinese chestnut and preventing the red spider attack, the leaves of 4 varieties with different levels of tannin content were harvested for comparative transcriptome analysis. In total, 335 differentially expressed genes (DEGs) were identified. For acquisition of gene functions and biological pathways they involved in, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed, and several DEGs were found to possibly participate in the tannins biosynthesis pathway and transport processes of precursors. In addition, according to the PlantTFDB database, some transcription factors were predicted among the DEGs, suggesting their role in regulation of tannins biosynthesis pathway. CONCLUSION: Our results provide valuable gene resources for understanding the biosynthesis and regulation mechanisms of tannins in foxtail millet, and pave the way for speeding up the breeding of low-tannin varieties through marker-assisted selection, which could be utilized for interplanting with Chinese chestnut trees to confer protection against red spider attack.
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Setaria (Planta)/química , Taninos/análisis , Transcriptoma/fisiología , Animales , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Fitomejoramiento , Hojas de la Planta/química , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/parasitología , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Setaria (Planta)/parasitología , Arañas/patogenicidad , Taninos/genética , Transcriptoma/genéticaRESUMEN
Glioblastomas (GBMs) are the most frequent primary malignancies in the central nervous system. Aberrant activation of WNT/ß-catenin signaling pathways is critical for GBM malignancy. However, the regulation of WNT/ß-catenin signaling cascades remains unclear. Presently, we observed the increased expression of ZEB2 and the decreased expression of miR-637 in GBM. The expression of miR-637 was negatively correlated with ZEB2 expression. miR-637 overexpression overcame the ZEB2-enhanced cell proliferation and G1/S phase transition. Besides, miR-637 suppressed the canonical WNT/ß-catenin pathways by targeting WNT7A directly. Gain- and loss-of-function experiments with U251 mice demonstrated that miR-637 inhibited cell proliferation and arrested the G1/S phase transition, leading to tumor growth suppression. The collective findings suggest that ZEB2 and WNT/ß-catenin cascades merge at miR-637, and the ectopic expression of miR-637 disturbs ZEB2/WNT/ß-catenin-mediated GBM growth. The findings provide new clues for improving ß-catenin-targeted therapy against GBM.
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Glioblastoma , MicroARNs , Animales , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Ratones , Vía de Señalización Wnt , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , beta CateninaRESUMEN
Carbon-based catalysts have the advantages of biological cleaning, eco-friendly and cost-effective in water treatment. While, nitrogen doped biochar promotes the development of non-radical peroxymonosulfate (PMS) activation in environmental remediation. Thus, three-dimensional sponge-like porous Fe and N co-doped biochar (Fe/CN-30) with high catalytic activity for PMS activation was synthesized. In a wide pH range (1-11), the Fe/CN-30 catalyst can efficiently degrade tetracycline (TC) with a small amount of PMS. The non-radical pathways are prominent in the TC decomposition process according to the quenching experiments, electron paramagnetic resonance (EPR) and gas chromatograph-mass spectrometer (GC-MS) analysis, in which the contribution of high-valent iron-oxo species (Fe(IV) = O) was dominant. X-ray photoelectron spectroscopy and reaction kinetic experiments confirmed that the coordination sites of Fe and N in the Fe/CN-30 are the reactive centers for TC degradation. Moreover, the successive addition of low concentration PMS into the system was confirmed to favor the PMS utilization, and the high selectivity of the Fe/CN-30 was confirmed by the analysis of pollutant structure. Furthermore, by-products of TC degradation in the Fe/CN-30/PMS system and the possible TC degradation pathways were proposed via liquid chromatography-mass spectrometry (LC-MS). Therefore, this study dedicates to providing new insights into the non-radical pathway-catalyzed AOPs.
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Peróxidos , Tetraciclina , Antibacterianos , Catálisis , Peróxidos/químicaRESUMEN
BACKGROUND: The Miro Health Mobile Assessment Platform consists of self-administered neurobehavioral and cognitive assessments that measure behaviors typically measured by specialized clinicians. OBJECTIVE: To evaluate the Miro Health Mobile Assessment Platform's concurrent validity, test-retest reliability, and mild cognitive impairment (MCI) classification performance. METHOD: Sixty study participants were evaluated with Miro Health version V.2. Healthy controls (HC), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) ages 64-85 were evaluated with version V.3. Additional participants were recruited at Johns Hopkins Hospital to represent clinic patients, with wider ranges of age and diagnosis. In all, 90 HC, 21 aMCI, 17 naMCI, and 15 other cases were evaluated with V.3. Concurrent validity of the Miro Health variables and legacy neuropsychological test scores was assessed with Spearman correlations. Reliability was quantified with the scores' intraclass correlations. A machine-learning algorithm combined Miro Health variable scores into a Risk score to differentiate HC from MCI or MCI subtypes. RESULTS: In HC, correlations of Miro Health variables with legacy test scores ranged 0.27-0.68. Test-retest reliabilities ranged 0.25-0.79, with minimal learning effects. The Risk score differentiated individuals with aMCI from HC with an area under the receiver operator curve (AUROC) of 0.97; naMCI from HC with an AUROC of 0.80; combined MCI from HC with an AUROC of 0.89; and aMCI from naMCI with an AUROC of 0.83. CONCLUSION: The Miro Health Mobile Assessment Platform provides valid and reliable assessment of neurobehavioral and cognitive status, effectively distinguishes between HC and MCI, and differentiates aMCI from naMCI.