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1.
Cell ; 186(7): 1398-1416.e23, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36944331

RESUMEN

CD3δ SCID is a devastating inborn error of immunity caused by mutations in CD3D, encoding the invariant CD3δ chain of the CD3/TCR complex necessary for normal thymopoiesis. We demonstrate an adenine base editing (ABE) strategy to restore CD3δ in autologous hematopoietic stem and progenitor cells (HSPCs). Delivery of mRNA encoding a laboratory-evolved ABE and guide RNA into a CD3δ SCID patient's HSPCs resulted in a 71.2% ± 7.85% (n = 3) correction of the pathogenic mutation. Edited HSPCs differentiated in artificial thymic organoids produced mature T cells exhibiting diverse TCR repertoires and TCR-dependent functions. Edited human HSPCs transplanted into immunodeficient mice showed 88% reversion of the CD3D defect in human CD34+ cells isolated from mouse bone marrow after 16 weeks, indicating correction of long-term repopulating HSCs. These findings demonstrate the preclinical efficacy of ABE in HSPCs for the treatment of CD3δ SCID, providing a foundation for the development of a one-time treatment for CD3δ SCID patients.


Asunto(s)
Inmunodeficiencia Combinada Grave , Linfocitos T , Humanos , Animales , Ratones , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/terapia , Edición Génica , Ratones SCID , Complejo CD3 , Receptores de Antígenos de Linfocitos T/genética
2.
Cell ; 146(6): 889-903, 2011 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-21925314

RESUMEN

Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.


Asunto(s)
Aberraciones Cromosómicas , Reparación del ADN , Discapacidades del Desarrollo/genética , Neoplasias/genética , Secuencia de Bases , Niño , Preescolar , Rotura Cromosómica , Hibridación Genómica Comparativa , Replicación del ADN , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Datos de Secuencia Molecular
3.
Nucleic Acids Res ; 51(18): 10026-10040, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37650645

RESUMEN

Thermococcus onnurineus NA1, a hyperthermophilic carboxydotrophic archaeon, produces H2 through CO oxidation catalyzed by proteins encoded in a carbon monoxide dehydrogenase (CODH) gene cluster. TON_1525 with a DNA-binding helix-turn-helix (HTH) motif is a putative repressor regulating the transcriptional expression of the codh gene cluster. The T55I mutation in TON_1525 led to enhanced H2 production accompanied by the increased expression of genes in the codh cluster. Here, TON_1525 was demonstrated to be a dimer. Monomeric TON_1525 adopts a novel 'eighth note' symbol-like fold (referred to as 'eighth note' fold regulator, EnfR), and the dimerization mode of EnfR is unique in that it has no resemblance to structures in the Protein Data Bank. According to footprinting and gel shift assays, dimeric EnfR binds to a 36-bp pseudo-palindromic inverted repeat in the promoter region of the codh gene cluster, which is supported by an in silico EnfR/DNA complex model and mutational studies revealing the implication of N-terminal loops as well as HTH motifs in DNA recognition. The DNA-binding affinity of the T55I mutant was lowered by ∼15-fold, for which the conformational change of N-terminal loops is responsible. In addition, transcriptome analysis suggested that EnfR could regulate diverse metabolic processes besides H2 production.

4.
Nano Lett ; 24(37): 11504-11511, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39177953

RESUMEN

Ice, one of the most enigmatic materials on Earth, exhibits diverse polymorphism, with research mainly focusing on the most commonly observed phases: hexagonal ice (Ih), cubic ice (Ic), and stacking-disordered ice (Isd). While their formation or structural changes are crucial for advancements in cloud science, climate modeling, and cryogenic technology, the molecular mechanisms driving these phenomena remain unexplored. Herein, utilizing cryogenic transmission electron microscopy, we investigate the formation of ice at two different temperatures, demonstrating a size-dependent phase shift from Ic to Isd. Furthermore, a relatively metastable cubic phase in Isd transitions to a hexagonal phase under electron beam radiation. This transition, facilitated by crystal defects, contrasts with perfect crystalline Ic, which maintains its original phase, emphasizing the importance of defects in polymorphic phase transitions. Our findings provide novel insights on phase control during the ice growth processes and polymorphic phase transitions from the cubic-to-hexagonal phases.

5.
Nano Lett ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557080

RESUMEN

Modern semiconductor fabrication is challenged by difficulties in overcoming physical and chemical constraints. A major challenge is the wet etching of dummy gate silicon, which involves the removal of materials inside confined spaces of a few nanometers. These chemical processes are significantly different in the nanoscale and bulk. Previously, electrical double-layer formation, bubble entrapment, poor wettability, and insoluble intermediate precipitation have been proposed. However, the exact suppression mechanisms remain unclear due to the lack of direct observation methods. Herein, we investigate limiting factors for the etching kinetics of silicon with tetramethylammonium hydroxide at the nanoscale by using liquid-phase transmission electron microscopy, three-dimensional electron tomography, and first-principles calculations. We reveal suppressed chemical reactions, unstripping phenomena, and stochastic etching behaviors that have never been observed on a macroscopic scale. We expect that solutions can be suggested from this comprehensive insight into the scale-dependent limiting factors of fabrication.

6.
J Infect Dis ; 229(6): 1722-1727, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38114088

RESUMEN

Immunocompromised patients with coronavirus disease 2019 were prospectively enrolled from March to November 2022 to understand the association between antibody responses and severe acute respiratory syndrome coronavirus 2 shedding. A total of 62 patients were analyzed, and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific immunoglobulin G (IgG) antibodies (both P < .001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = .04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Huésped Inmunocomprometido , Inmunoglobulina G , SARS-CoV-2 , Esparcimiento de Virus , Humanos , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anciano , ARN Viral , Adulto , Formación de Anticuerpos/inmunología
7.
J Am Chem Soc ; 146(28): 19369-19376, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38965837

RESUMEN

Self-assembly of conjugated polymers offers a powerful method to prepare semiconducting two-dimensional (2D) nanosheets for optoelectronic applications. However, due to the typical biaxial growth behavior of the polymer self-assembly, independent control of the width and length of 2D sheets has been challenging. Herein, we present a greatly accelerated crystallization-driven self-assembly (CDSA) system of polyacetylene-based conjugated polymer to produce 2D semiconducting nanorectangles with precisely controllable dimensions. In detail, rectangular 2D seeds with tunable widths of 0.2-1.3 µm were produced by changing the cosolvent% and grown in the length direction by uniaxial living CDSA up to 11.8 µm. The growth rate was effectively enhanced by tuning the cosolvent%, seed concentration, and temperature, achieving up to 27-fold increase. Additionally, systematic kinetic investigation yielded empirical rate equations, elucidating the relationship between growth rate constant, cosolvent%, seed concentration, and seed width. Finally, the living CDSA allowed us to prepare penta-block comicelles with tunable width, length, and height.

8.
Small ; 20(4): e2304051, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37612793

RESUMEN

Quantum-dot light-emitting diodes (QD-LEDs) have gained attention as potential display technologies. However, the solvents used to dissolve a polymeric hole transport layer (HTL) are hazardous to both humans and the environment. Additionally, intermixing the HTL and QD layers presents a significant challenge when fabricating inverted QD-LEDs. Here, a green solvent selection procedure to achieve good device performance and environmental safety in QD-LEDs is established. This procedure utilizes Hansen solubility parameters and surface roughness to identify a set of solvents that do not lower the device performance by avoiding interlayer mixing or a rough interface. The CHEM21 solvent selection guide is used to screen for environmentally hazardous solvents. Finally, cyclopentanone (CPO) is selected as the optimal HTL solvent from among 16 candidates. Using CPO improves the maximum luminescence by ≈1.6 times and the maximum current efficiency by ≈12.6 times, compared to that of conventional devices using hazardous chlorobenzene. Solvent selection is critical for the fabrication of green and high-performance inverted QD-LEDs, particularly for large display panels that require n-type oxide thin-film transistors.

9.
Small ; : e2401594, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38860544

RESUMEN

Defect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH3COO)2·2H2O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m2 g-1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C2H4) permeability (281 Barrer) with a moderate ethylene/ethane (C2H4/C2H6) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C2H4/C2H6 separation.

10.
BMC Cancer ; 24(1): 909, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075471

RESUMEN

BACKGROUND: Advancements in the diagnosis, treatment, and surveillance of castration-resistant prostate cancer (CRPC) have progressed considerably, but a new biomarker that combines existing clinical and pathological data could be useful for a more precise diagnosis and prognosis. Some investigations have found that extracellular vesicle (EV)-derived miRNAs play crucial roles in various types of malignant tumors. The objective of this study was to explore EV miRNA and identify its biologic function as a biomarker for the diagnosis and prognosis of CRPC. METHODS: Plasma samples were collected from five healthy donors (Control, CT) and 17 CRPC patients, categorizing into two groups based on their endocrine treatment response: partial response (PR; n = 10) and progressive disease (PD; n = 7). Candidate extracellular vesicle (EV) miRNAs were identified using miRNA microarray and RT-qPCR. The biological functions of the selected miRNAs were evaluated using the MTT assay, wound healing assay, trans-well assay, and RNA sequencing in CRPC cells after transient miRNA expression. RESULTS: Microarray analysis revealed a significant downregulation of EV-miR-6880-5p in the PD samples compared to both CT and PR samples (p < 0.01). The expression of EV-miR-6880-5p in CRPC patients was decreased compared with that CT group (p = 0.0336) using RT-qPCR. In the PR group, EV-miR-6880-5p was increased at follow-up compared with the baseline (p = 0.2803), while in the PD group, it decreased at follow-up compared with the baseline samples (p = 0.4356). Furthermore, overexpression of miR-6880-5p hampered cell proliferation, migration, and invasion, downregulated pathways associated with tumor progression, and simultaneously upregulated pathways associated with cell growth and apoptosis in CRPC cells. CONCLUSIONS: EV-miR-6880-5p shows promise as a prognostic biomarker in patients with CRPC. Further, prospective validations are necessary to evaluate the potential of these candidate miRNAs.


Asunto(s)
Biomarcadores de Tumor , Vesículas Extracelulares , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroARNs/sangre , MicroARNs/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Pronóstico , Anciano , Persona de Mediana Edad , Línea Celular Tumoral , Proliferación Celular , Perfilación de la Expresión Génica/métodos , Movimiento Celular/genética
11.
Theor Appl Genet ; 137(9): 202, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39134894

RESUMEN

KEY MESSAGE: Pigmentation changes in canopy leaves were first reported, and subsequent genetic analyses identified a major QTL associated with levels of pigmentation changes, suggesting Glyma.06G202300 as a candidate gene. An unexpected reddish-purple pigmentation in upper canopy leaves was discovered during the late reproductive stages in soybean (Glycine max L.) genotypes. Two sensitive genotypes, 'Uram' and PI 96983, exhibited anomalous canopy leaf pigmentation changes (CLPC), while 'Daepung' did not. The objectives of this study were to: (i) characterize the physiological features of pigmented canopy leaves compared with non-pigmented leaves, (ii) evaluate phenotypic variation in a combined recombinant inbred line (RIL) population (N = 169 RILs) under field conditions, and (iii) genetically identify quantitative trait loci (QTL) for CLPC via joint population linkage analysis. Comparison between pigmented and normal leaves revealed different Fv/Fm of photosystem II, hyperspectral reflectance, and cellular properties, suggesting the pigmentation changes occur in response to an undefined abiotic stress. A highly significant QTL was identified on chromosome 6, explaining ~ 62.8% of phenotypic variance. Based on the QTL result, Glyma.06G202300 encoding flavonoid 3'-hydroxylase (F3'H) was identified as a candidate gene. In both Uram and PI 96983, a 1-bp deletion was confirmed in the third exon of Glyma.06G202300 that results in a premature stop codon in both Uram and PI 96983 and a truncated F3'H protein lacking important domains. Additionally, gene expression analyses uncovered significant differences between pigmented and non-pigmented leaves. This is the first report of a novel symptom and an associated major QTL. These results will provide soybean geneticists and breeders with valuable knowledge regarding physiological changes that may affect soybean production. Further studies are required to elucidate the causal environmental stress and the underlying molecular mechanisms.


Asunto(s)
Mapeo Cromosómico , Genotipo , Glycine max , Fenotipo , Pigmentación , Hojas de la Planta , Sitios de Carácter Cuantitativo , Glycine max/genética , Glycine max/crecimiento & desarrollo , Glycine max/fisiología , Hojas de la Planta/genética , Pigmentación/genética , Ligamiento Genético
12.
Cell Commun Signal ; 22(1): 138, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374138

RESUMEN

BACKGROUND: Applications of nonthermal plasma have expanded beyond the biomedical field to include antibacterial, anti-inflammatory, wound healing, and tissue regeneration. Plasma enhances epithelial cell repair; however, the potential damage to deep tissues and vascular structures remains under investigation. RESULT: This study assessed whether liquid plasma (LP) increased nitric oxide (NO) production in human umbilical vein endothelial cells by modulating endothelial NO synthase (eNOS) phosphorylation and potential signaling pathways. First, we developed a liquid plasma product and confirmed the angiogenic effect of LP using the Matrigel plug assay. We found that the NO content increased in plasma-treated water. NO in plasma-treated water promoted cell migration and angiogenesis in scratch and tube formation assays via vascular endothelial growth factor mRNA expression. In addition to endothelial cell proliferation and migration, LP influenced extracellular matrix metabolism and matrix metalloproteinase activity. These effects were abolished by treatment with NG-L-monomethyl arginine, a specific inhibitor of NO synthase. Furthermore, we investigated the signaling pathways mediating the phosphorylation and activation of eNOS in LP-treated cells and the role of LKB1-adenosine monophosphate-activated protein kinase in signaling. Downregulation of adenosine monophosphate-activated protein kinase by siRNA partially inhibited LP-induced eNOS phosphorylation, angiogenesis, and migration. CONCLUSION: The present study suggests that LP treatment may be a novel strategy for promoting angiogenesis in vascular damage. Video Abstract.


Asunto(s)
Matriz Extracelular , Óxido Nítrico Sintasa de Tipo III , Plasma , Lesiones del Sistema Vascular , Humanos , Adenosina Monofosfato/metabolismo , Adenosina Monofosfato/farmacología , Angiogénesis , Matriz Extracelular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa/farmacología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Proteínas Quinasas/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Lesiones del Sistema Vascular/metabolismo , Lesiones del Sistema Vascular/terapia , Plasma/metabolismo
13.
Langmuir ; 40(6): 3213-3221, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38314692

RESUMEN

Water molecules can bind to zwitterionic polymers, such as carboxybetaine and sulfobetaine, forming strong hydration layers along the polymer chains. Such hydration layers act as a barrier to impede the attachment of marine fouling organisms; therefore, zwitterionic polymer coatings have been of considerable interest as marine antifouling coatings. However, recent studies have shown that severe adsorption of marine sediments occurs on zwitterionic-polymer-coated surfaces, resulting in the degradation of their marine antifouling performance. Therefore, a novel approach for forming amphiphilic zwitterionic polymers using zwitterionic and hydrophobic monomers is being investigated to simultaneously inhibit both sediment adsorption and marine fouling. In this study, amphiphilic zwitterionic thin polymer brushes composed of sulfobetaine methacrylate (SBMA) and trifluoroethyl methacrylate (TFEMA) were synthesized on Si/SiO2 surfaces via surface-initiated atom transfer radical polymerization. For this, a facile metal-ion-mediated method was developed for immobilizing polymerization initiators on solid substrates to subsequently form poly(SBMA-co-TFEMA) brushes on the initiator-coated substrate surface. Poly(SBMA-co-TFEMA) brushes with various SBMA/TFEMA ratios were prepared to determine the composition at which both marine diatom adhesion and sediment adsorption can be prevented effectively. The results indicate that poly(SBMA-co-TFEMA) brushes prepared with an SBMA/TFEMA ratio of 3:7 effectively inhibit both sediment adsorption and marine diatom adhesion, thereby exhibiting balanced marine antifouling properties. Thus, the findings of this study provide important insights into the design of amphiphilic marine antifouling materials.

14.
Langmuir ; 40(37): 19644-19653, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39219107

RESUMEN

The antifouling efficacy of hydrophilic polymer coatings is closely related to their surface charge. Many biological foulants such as mammalian cells and marine microalgae possess a negative surface charge, discouraging the use of positively charged polymer coatings for antifouling purposes. Instead, electrically neutral yet hydrophilic polymers have been widely employed, leveraging hydration layers to create a barrier against fouling. However, challenges arise in marine environments where both living marine organisms and sediments can adhere to solid surfaces, rendering previous findings less directly applicable. This study investigates the impact of a polymer coating surface charge on marine antifouling properties. Polymer brushes with various charges are applied to solid substrates, and the adhesion behavior of marine diatoms is assessed under both marine sediment-free and marine sediment conditions. The results underscore the effectiveness of negatively charged polymer brush coatings in marine antifouling, regardless of sediment presence.

15.
Langmuir ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287557

RESUMEN

Surface coating with dopamine (DA) has received significant attention over the past decade due to its compatibility with other surface coating techniques and versatility, making it applicable to solid surfaces regardless of substrate and shape. Much effort has been made to elucidate the origin of its surface coating capability, and as a result, many important factors affecting the coating properties have been determined. For example, it has been reported that the length of the carbon chain between catechol and amino groups, the attachment of specific functional groups to the catechol ring and amino group, and the replacement of the amino group with another functional group can affect the surface coating properties of DA. Despite these various attempts, there are still many factors that remain unknown. In this study, we investigate the effect of N-alkylation on DA coating. N-Ethyl-DA, N-propyl-DA, and N-isopropyl-DA are newly synthesized through simple organic reactions, and the coating efficiency of DA derivatives is compared with nucleophilicity and steric bulkiness. As a result, the coating efficiency of N-ethyl-DA and N-propyl-DA is lower than for pristine DA and N-methyl-DA, but it is possible to coat solid surfaces with alkyl-functionalized DA. In contrast, the coating with sterically bulky N-isopropyl-DA is almost unsuccessful.

16.
RNA Biol ; 21(1): 1-15, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38372062

RESUMEN

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.


Asunto(s)
MicroARNs , Humanos , Animales , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Células HeLa , Silenciador del Gen , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , ARN Mensajero/genética
17.
Virus Genes ; 60(5): 563-567, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38907176

RESUMEN

The cotton leafroll dwarf virus (CLDV), an important viral pathogen responsible for substantial losses in cotton crops, has recently emerged in the United States (US). Although CLDV shares similarities with other members of the genus Polerovirus in terms of encoded proteins, their functional characteristics remain largely unexplored. In this study, we expressed and analyzed each protein encoded by CLDV to determine its intracellular localization using fluorescence protein fusion. We also evaluated their potential to induce plant responses, such as the induction of hypersensitive response-like necrosis and the generation of reactive oxygen species. Our findings show that the proteins encoded by CLDV exhibit comparable localization patterns and elicit similar robust plant responses as observed with cognate proteins from other viruses within the genus Polerovirus. This study contributes to our understanding of the functional repertoire of genes carried by Polerovirus members, particularly to CLDV that has recently emerged as a widespread viral pathogen infecting cotton in the US.


Asunto(s)
Gossypium , Luteoviridae , Enfermedades de las Plantas , Proteínas Virales , Gossypium/virología , Luteoviridae/genética , Luteoviridae/patogenicidad , Enfermedades de las Plantas/virología , Proteínas Virales/genética , Proteínas Virales/metabolismo , Especies Reactivas de Oxígeno/metabolismo
18.
Int J Colorectal Dis ; 39(1): 94, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902500

RESUMEN

PURPOSE: To examine the ability of generative artificial intelligence (GAI) to answer patients' questions regarding colorectal cancer (CRC). METHODS: Ten clinically relevant questions about CRC were selected from top-rated hospitals' websites and patient surveys and presented to three GAI tools (Chatbot Generative Pre-Trained Transformer [GPT-4], Google Bard, and CLOVA X). Their responses were compared with answers from the CRC information book. Response evaluation was performed by two groups, each consisting of five healthcare professionals (HCP) and patients. Each question was scored on a 1-5 Likert scale based on four evaluation criteria (maximum score, 20 points/question). RESULTS: In an analysis including only HCPs, the information book scored 11.8 ± 1.2, GPT-4 scored 13.5 ± 1.1, Google Bard scored 11.5 ± 0.7, and CLOVA X scored 12.2 ± 1.4 (P = 0.001). The score of GPT-4 was significantly higher than those of the information book (P = 0.020) and Google Bard (P = 0.001). In an analysis including only patients, the information book scored 14.1 ± 1.4, GPT-4 scored 15.2 ± 1.8, Google Bard scored 15.5 ± 1.8, and CLOVA X scored 14.4 ± 1.8, without significant differences (P = 0.234). When both groups of evaluators were included, the information book scored 13.0 ± 0.9, GPT-4 scored 14.4 ± 1.2, Google Bard scored 13.5 ± 1.0, and CLOVA X scored 13.3 ± 1.5 (P = 0.070). CONCLUSION: The three GAIs demonstrated similar or better communicative competence than the information book regarding questions related to CRC surgery in Korean. If high-quality medical information provided by GAI is supervised properly by HCPs and published as an information book, it could be helpful for patients to obtain accurate information and make informed decisions.


Asunto(s)
Inteligencia Artificial , Neoplasias Colorrectales , Comunicación , Humanos , Neoplasias Colorrectales/cirugía , Masculino , Femenino , Persona de Mediana Edad , Encuestas y Cuestionarios , Cirugía Colorrectal
19.
Colorectal Dis ; 26(7): 1405-1414, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38881232

RESUMEN

AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).


Asunto(s)
Neoplasias Colorrectales , Inestabilidad de Microsatélites , Mutación , Proteínas Proto-Oncogénicas B-raf , Adulto , Anciano , Femenino , Humanos , Masculino , Factores de Edad , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Estudios Transversales , GTP Fosfohidrolasas/genética , Proteínas de la Membrana/genética , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
20.
Nature ; 559(7712): 77-82, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29942075

RESUMEN

Developing adaptive materials with geometries that change in response to external stimuli provides fundamental insights into the links between the physical forces involved and the resultant morphologies and creates a foundation for technologically relevant dynamic systems1,2. In particular, reconfigurable surface topography as a means to control interfacial properties3 has recently been explored using responsive gels4, shape-memory polymers5, liquid crystals6-8 and hybrid composites9-14, including magnetically active slippery surfaces12-14. However, these designs exhibit a limited range of topographical changes and thus a restricted scope of function. Here we introduce a hierarchical magneto-responsive composite surface, made by infiltrating a ferrofluid into a microstructured matrix (termed ferrofluid-containing liquid-infused porous surfaces, or FLIPS). We demonstrate various topographical reconfigurations at multiple length scales and a broad range of associated emergent behaviours. An applied magnetic-field gradient induces the movement of magnetic nanoparticles suspended in the ferrofluid, which leads to microscale flow of the ferrofluid first above and then within the microstructured surface. This redistribution changes the initially smooth surface of the ferrofluid (which is immobilized by the porous matrix through capillary forces) into various multiscale hierarchical topographies shaped by the size, arrangement and orientation of the confining microstructures in the magnetic field. We analyse the spatial and temporal dynamics of these reconfigurations theoretically and experimentally as a function of the balance between capillary and magnetic pressures15-19 and of the geometric anisotropy of the FLIPS system. Several interesting functions at three different length scales are demonstrated: self-assembly of colloidal particles at the micrometre scale; regulated flow of liquid droplets at the millimetre scale; and switchable adhesion and friction, liquid pumping and removal of biofilms at the centimetre scale. We envision that FLIPS could be used as part of integrated control systems for the manipulation and transport of matter, thermal management, microfluidics and fouling-release materials.

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