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1.
Adv Healthc Mater ; : e2401085, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38796738

RESUMEN

Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of ß-galactosidase (ß-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.

2.
Int J Biol Macromol ; 267(Pt 2): 131462, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614163

RESUMEN

The rapid development of the industry has led to the destruction of the earth's ozone layer, resulting in an increasingly serious problem of excessive ultraviolet radiation. Exploring effective measures to address these problems has become a hot topic. Lignin shows promise in the design and preparation of anti-ultraviolet products due to its inherent properties. However, it is important to investigate way to enhance the reactivity of lignin and determine its application form in related products. In this study, phenolic reactions with tea polyphenols were conducted through acid-catalyzed conversion, utilizing organic solvent lignin as the primary material. The phenolic hydroxyl content of the original lignin increased significantly by 218.8 %, resulting in notable improvements in UV resistance and oxidation resistance for phenolic lignin. Additionally, micro-nanocapsule emulsions were formed using phenolic lignin particles as surfactants through ultrasonic cavitation with small-molecule sunscreens. A bio-based sunscreen was prepared with phenolated lignin micro-nanocapsules as the active ingredient, achieving an SPF 100.2 and demonstrating excellent stability. The sunscreen also exhibited strong antioxidant properties and impermeability, ensuring user safety. This research offers a current solution for improving the application of lignin in sunscreens while also broadening the potential uses of plant-based materials in advanced functional products.


Asunto(s)
Lignina , Oxidación-Reducción , Polifenoles , Protectores Solares , , Rayos Ultravioleta , Lignina/química , Polifenoles/química , Catálisis , Té/química , Protectores Solares/química , Protectores Solares/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Ácidos/química
3.
Carbohydr Polym ; 336: 122138, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38670763

RESUMEN

Water-soluble silver nanoclusters (AgNCs) as a new type of fluorescent material have attracted much attention for their remarkable optical properties and excellent cytocompatibility. However, it is still challenging to synthesize water-soluble AgNCs with good cytocompatibility and excellent fluorescence. Herein, the dialdehyde nanofibrillated cellulose (DANFC)- reduced water-soluble AgNCs capped by glutathione (GSH) with tunable fluorescence emissions were first reported. The DANFC provides a mild reduction environment and crystal growth system for the coordination between silver ions and GSH compared to conventional methods using strong reducing agents. The AgNCs with intense red fluorescence (R-AgNCs@GSH, size ∼2.24 nm) and green fluorescence (G-AgNCs@GSH, size ∼1.93 nm) were produced by varying the ratios of silver sources and ligands, and could maintain stable fluorescence intensity over 6 months. Moreover, the CCK-8 study demonstrated that the R-AgNCs@GSH and G-AgNCs@GSH reduced by DANFC of excellent cytocompatibility (cell viability >90 %) and enable precise multicolor intracellular imaging of Hela cells in 1 h. This work proposes a novel method to synthesize water-soluble AgNCs with tunable fluorescence emission at room temperature based on the classical silver- mirror reaction (SMR) using DANFC as reducing agent, and the synthesized fluorescent AgNCs have great potential as novel luminescent nanomaterials in biological research.


Asunto(s)
Celulosa , Nanopartículas del Metal , Plata , Solubilidad , Agua , Plata/química , Humanos , Celulosa/química , Células HeLa , Nanopartículas del Metal/química , Agua/química , Glutatión/química , Nanofibras/química , Supervivencia Celular/efectos de los fármacos , Imagen Óptica/métodos , Fluorescencia , Colorantes Fluorescentes/química
4.
Int J Biol Macromol ; 262(Pt 2): 130016, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38365139

RESUMEN

In this study, we investigated the structural characterization and biological activities of Bletilla striata polysaccharides (BSPs) for their role as antioxidants and anti-melanogenesis agents in skin healthcare protection. Three neutral polysaccharides (BSP-1, BSP-2, and BSP-3) with molecular weights of 269.121 kDa, 57.389 kDa, and 28.153 kDa were extracted and purified. Their structural characteristics were analyzed by ion chromatography, GC-MS, and 1D/2D NMR. The results showed that BSP-1, which constitutes the major part of BSPs, was composed of α-D-Glcp, ß-D-Glcp, ß-D-Manp, and 2-O-acetyl-ß-D-Manp, with the branched-chain accompanied by ß-D-Galp and α-D-Glcp. BSP-1, BSP-2, and BSP-3 can enhance the total antioxidant capacity of skin fibroblasts with non-toxicity. Meanwhile, BSP-1, BSP-2, and BSP-3 could significantly inhibit the proliferative activity of melanoma cells. Among them, BSP-1 and BSP-2 showed more significance in anti-melanogenesis, tyrosinase inhibition activity, and cell migration inhibition. BSPs have effective antioxidant capacity and anti-melanogenesis effects, which should be further emphasized and developed as skin protection components.


Asunto(s)
Antioxidantes , Orchidaceae , Antioxidantes/farmacología , Antioxidantes/química , Orchidaceae/química , Espectroscopía de Resonancia Magnética , Peso Molecular , Polisacáridos/química
5.
ACS Appl Mater Interfaces ; 15(30): 36877-36887, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37463316

RESUMEN

Lung cancer (LC) is a major cause of mortality among malignant tumors. Early diagnosis through lipidomic profiling can improve prognostic outcomes. In this study, a uniform PbS/Au-layered substrate that enhances the laser desorption/ionization process, an interfacial process triggered on the substrate surface upon laser excitation, was designed to efficiently characterize the lipidomic profiles of LC patient serum. By controlling the stacking arrangement and particle sizes of PbS QDs and AuNPs, the optimized substrate promotes the generation of excited electrons and creates an enhanced electric field that polarizes analyte molecules, facilitating ion adduction formation ([M + Na]+ and [M + K]+) and enhancing detection sensitivity down to the femtomole level. Combining multivariate statistics and machine learning, a distinct lipidomic biomarker panel is successfully identified for the early diagnosis and staging of LC, with an accurate prediction validated by an area under the curve of 0.9479 and 0.9034, respectively. We also found that 18 biomarkers were significantly correlated with six metabolic pathways associated with LC. These results demonstrate the potential of this innovative PbS/Au-layered substrate as a sensitive platform for accurate diagnosis of LC and facilitate the development of lipidomic-based diagnostic tools for other cancers.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas del Metal , Humanos , Lipidómica , Oro/química , Detección Precoz del Cáncer , Nanopartículas del Metal/química , Neoplasias Pulmonares/metabolismo , Biomarcadores , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
6.
Small ; 19(40): e2301353, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37282825

RESUMEN

2D carbon nanomaterials such as graphene, carbon nanosheets, and their derivatives, representing the emerging class of advanced multifunctional materials, have gained great research interest because of their extensive applications ranging from electrochemistry to catalysis. However, sustainable and scalable synthesis of 2D carbon nanosheets (CNs) with hierarchical architecture and irregular structure via a green and low-cost strategy remains a great challenge. Herein, prehydrolysis liquor (PHL), an industrial byproduct of the pulping industry, is first employed to synthesize CNs via a simple hydrothermal carbonization technique. After mild activation with NH4 Cl and FeCl3 , the as-prepared activated CNs (A-CN@NFe) display an ultrathin structure (≈3 nm) and a desirable specific surface area (1021 m2 g-1 ) with hierarchical porous structure, which enables it to be both electroactive materials and structural support materials in nanofibrillated cellulose/A-CN@NFe/polypyrrole (NCP) nanocomposite, and thus endowing nanocomposite with impressive capacitance properties of 2546.3 mF cm-2 at 1 mA cm-2 . Furthermore, the resultant all-solid-state symmetric supercapacitor delivers a satisfactory energy storage ability of 90.1 µWh cm-2 at 250.0 µW cm-2 . Thus, this work not only opens a new window for sustainable and scalable synthesis of CNs, but also offers a double profits strategy for energy storage and biorefinery industry.

7.
Sci Total Environ ; 890: 164234, 2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37230341

RESUMEN

Polycyclic Aromatic Hydrocarbons (PAHs) and Polychlorinated Biphenyls (PCBs) are significant components of persistent organic pollutants (POPs) and pose a threat to both ecosystems and human health. To explore their spatial distribution, origins, and risk assessment, we collected 25 glacial meltwater and downstream river water samples in the eastern Tibetan Plateau (including the Qilian Mountains in the northeast) during the summer of 2022 (June-July). Our results showed that ∑PAHs and ∑PCBs were present in a wide range from ND-1380 ng/L and ND-1421 ng/L, respectively. Compared to other studies worldwide, the ∑PAHs and ∑PCBs in the Hengduan Mountains were at high levels. The PAHs and PCBs mainly consisted of low-molecular-weight homologs, including Ace, Flu, Phe, and PCB52. Phe was the primary component of PAHs. Glacial meltwater samples generally exhibited low concentration of PAHs and PCB52, whereas downstream river water samples typically showed high concentration of PAHs and PCB52. We attributed this characteristic to the influence of pollutants physicochemical properties, altitude effect, long-range transport (LRT), and local environmental conditions. In the eastern Tibetan Plateau glacier basin (especially in the Hailuogou watersheds), the concentration of PAHs and PCB52 in runoff generally increased with decreasing elevation. We believe that the primary factor affecting the concentration of PAHs and PCB52 in the region is the difference in local human activity inputs from various altitudes. The composition characteristics of PAHs and PCBs suggested that incomplete coal combustion and coking discharge mainly caused PAHs, while the combustion of coal and charcoal and the release of capacitors primarily caused PCBs. We assessed the carcinogenic risk of PAHs and PCBs in the glacier basin of the TP and found that the potential threat of PAHs was stronger than that of PCBs. Overall, this study provides new insights into the ecological security of water resources in eastern Tibetan Plateau. It is significant for controlling PAHs and PCBs emissions, assessing the ecological environment of the glacier watershed, and regional human health.


Asunto(s)
Bifenilos Policlorados , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Humanos , Bifenilos Policlorados/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Tibet , Ecosistema , Agua , Medición de Riesgo , Carbón Mineral , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis
8.
STAR Protoc ; 4(2): 102281, 2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149859

RESUMEN

Lower-grade gliomas exhibit a high prevalence of isocitrate dehydrogenase 1 (IDH1) mutations, but faithful models for studying these tumors are lacking. Here, we present a protocol to establish a genetically engineered mouse (GEM) model of grade 3 astrocytoma driven by the Idh1R132H oncogene. We describe steps for breeding compound transgenic mice and intracranially delivering adeno-associated virus particles, followed by post-surgical surveillance via magnetic resonance imaging. This protocol enables the generation and use of a GEM to study lower-grade IDH-mutant gliomas. For complete details on the use and execution of this protocol, please refer to Shi et al. (2022).1.

9.
J Colloid Interface Sci ; 630(Pt A): 604-617, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36272215

RESUMEN

The preparation of carboxylated cellulose nanocrystals (cCNCs) and their stabilization in oil-in-water (O/W) Pickering emulsions hold great potential for application and research value. In this work, a novel integrated oxidation strategy was proposed to prepare needle-like cCNCs by sodium periodate (NaIO4)/Fenton (SF-cCNCs) with considerable yield (58.58 %), plentiful carboxyl groups (1.28 mmol/g), and high crystallinity (83.3 %). The distinctive features of smaller size and high viscosity accelerated the as-prepared SF-cCNCs to be used in stabilizing Pickering emulsion. Moreover, the effects of oil-water ratio (OWR), SF-cCNCs content, pH, and sodium chloride (NaCl) content on the stability of SF-cCNCs-stabilized Pickering emulsions were also investigated systematically. Interestingly, the stability of the as-obtained emulsions was dependent on pH and salt. Afterwards, the rheological behaviors validated that the emulsion viscosity increased rapidly after adding NaCl, which was dominated by the elastic behavior. Finally, the main stabilization mechanism was confirmed to be interfacial adsorption of SF-cCNCs rather than the formation of spatial network structures between droplets. This study reports a synthetic strategy to efficiently prepare SF-cCNCs, endowing the SF-cCNCs stabilized Pickering emulsion with environmentally friendly, long-term stable and highly anti-agglomeration abilities for cosmetics and food products.


Asunto(s)
Celulosa , Nanopartículas , Celulosa/química , Emulsiones/química , Cloruro de Sodio , Emulsionantes , Nanopartículas/química , Agua/química
10.
Talanta ; 253: 123912, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36115102

RESUMEN

In this work, we successfully constructed a label-free electrochemiluminescence (ECL) immunosensor for the detection of breast cancer marker antigen (CA15-3). In particular, 3,4,9,10-perylenetetracarboxylic acid (PTCA) is cleverly attached to the surface of silica spheres as a luminophore (NH2-SiO2-PTCA), which greatly alleviates the disadvantage of PTCA anti-induced aggregated luminescence and improves the ECL performance. Furthermore, Pt nanoparticles were used to dope CeO2 and introducing reduced graphene oxide (rGO) to prepare CeO2/Pt/rGO composites as a novel co-reaction accelerator. Among them, Pt nanoparticles were used to improve the electrical conductivity of CeO2, and the use of rGO as a substrate allows for a more uniform dispersion of CeO2 to increase the catalytic surface area, which effectively improves the performance of the co-reaction accelerator and thus increasing the ECL intensity of the PTCA/S2O82- system. Under the optimal conditions, the designed ECL immunosensor showed satisfactory results in the determination of CA15-3 with a linear range of 12.00 mU mL-1 - 120.00 U mL-1 and a low detection limit of 1.348 mU mL-1. Importantly, the resulting biosensor has good stability, high sensitivity and reliable reproducibility, suggesting its potential application in clinical research.


Asunto(s)
Técnicas Biosensibles , Dióxido de Silicio , Reproducibilidad de los Resultados , Inmunoensayo
11.
Cancer Cell ; 40(9): 939-956.e16, 2022 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-35985343

RESUMEN

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH-mutant gliomas. Mechanistically, this reflects an obligate dependence of glioma cells on the de novo pyrimidine synthesis pathway and mutant IDH's ability to sensitize to DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation.


Asunto(s)
Neoplasias Encefálicas , Glioma , Leucemia , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Inhibidores Enzimáticos/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/genética , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Ratones , Mutación , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Salicilanilidas , Triazoles
12.
Food Chem ; 397: 133682, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-35921700

RESUMEN

Soybean protein pastes were preheated for different times (20, 25 and 30 min) with l-cysteine to improve the printability and self-gelation properties and to explore the relationship between the degree of denaturation and the feasibility of microwave 3D printing. As the pre-denaturation degree increased, ordered secondary structures in proteins gradually decreased, and tertiary structures unfolded. Soybean protein printability, moulding quality increased, and soybean protein, which is not suitable for printing in its natural state, achieved self-gelling after 3D printing. Soybean protein pastes preheated for 25 min with l-cysteine achieved a complete hollow sphere structure compared to other formulations, while pastes preheated for 30 min formed a coarser structure, and blockage occurred during printing. The covalent bond of ε- (γ-glutamine) formed by the synergistic effect of transglutaminase (TGase) and microwaves was the main force driving the gel network structure formation. The most suitable pre-denaturation degree of soybean protein was quantitatively characterized as 57 %.


Asunto(s)
Microondas , Proteínas de Soja , Coloides , Cisteína , Geles/química , Impresión Tridimensional , Proteínas de Soja/química
13.
Talanta ; 246: 123523, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35550510

RESUMEN

Heterostructured construction is regarded as a valuable approach to improve photoelectrochemical (PEC) performances. Herein, porous hollow NiS@NiO spheres were prepared derived from the Ni(TCY) MOFs precursor. Photoactive TiO2 was coupled with as-prepared NiS@NiO to form a close heterojunction interface of NiS@NiO/TiO2. NiS@NiO/TiO2 modified ITO electrode (NiS@NiO/TiO2/ITO) displayed fiercely enhanced photocurrent response, which was 4687-fold than that of NiS@NiO/ITO (0.008 µA) and 8.5-fold than that of TiO2/ITO (4.41 µA), respectively. Remarkable PEC property could be ascribed to the hollow NiS@NiO spheres with thin-shell structure provided there is a larger active surface area for harvesting the visible light. Most importantly, the p-n type NiS@NiO/TiO2 heterojunction could lead to generating more photo-excited charge carriers (e-/h+) and efficiently hinder the recombination of carriers, resulting in significantly augmented photocurrent output. Based on this outstanding PEC property, NiS@NiO/TiO2/ITO electrode fabricated sensing platform (BSA/anti-CEA/NiS@NiO/TiO2/ITO, BSA=Bovine serum albumin) exhibited high sensitivity for monitoring CEA (Carcinoembryonic antigen). Wide linear detection range was from 0.001 to 45 ng mL-1 and with a low detection limit of 1.67 × 10-4 ng mL-1 (S/N = 3). Prepared biosensors also showed good reproducibility, stability and had satisfying specificity. Thus, the proposed NiS@NiO/TiO2 heterostructured composite afforded well-design and synthesis strategy for constructing high-performance photoactive materials from MOFs-derivate.


Asunto(s)
Técnicas Biosensibles , Antígeno Carcinoembrionario , Técnicas Electroquímicas/métodos , Reproducibilidad de los Resultados , Titanio/química
14.
Anal Chim Acta ; 1212: 339913, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35623791

RESUMEN

In this study, a porous hollow CdCoS2(2) microsphere was synthesized based on the ZIF-67-S MOFs derived method of sulfurization reaction and calcination process. Under visible light irradiation, the resulting CdCoS2(2) composite showed a markedly enhanced photoelectrochemical (PEC) response. The photocurrent value of the CdCoS2(2) modified ITO electrode was 93-fold and 41-fold than that of CoS and CdS materials, respectively. Promoting the photo-absorption ability by internal multilight scattering/reflection was due to the porous and hollow nature of CdCoS2(2). Furthermore, obtained CdCoS2(2) heterostructure in-situ with a close contact interface could facilitate the separation/migration of photo-induced carriers. The CdCoS2(2) was also mixed with Ag nanoparticles (NPs) to further improve the PEC response. Acetylcholinesterase (AChE) as a bio-recognition molecule was immobilized on the glutaraldehyde-chitosan (GLD-CS) modified CdCoS2(2)@Ag electrode surface by cross-linking effect. AChE could hydrolyze the acetylcholine chloride (ATCl) to produce an electron donor of thiocholine which led to the elevated photocurrent output. When the bioactivity of AChE was inhibited by the organophosphate pesticides (chlorpyrifos as substrate), the reduced production of thiocholine resulted in a decline in photocurrent. Under optimal conditions, the structured AChE/GLD-CS/CdCoS2(2)@Ag/ITO sensing platform was successfully achieved for chlorpyrifos detection. The wide linear response range was from 0.001 to 270 µg mL-1 and with a low detection limit of 0.57 ng mL-1. The proposed PEC biosensor also exhibited excellent selectivity and good stability, demonstrating the designed porous hollow CdCoS2(2)@Ag heterostructured composite promised to be a great application in the PEC sensors.


Asunto(s)
Compuestos de Cadmio , Cloropirifos , Nanopartículas del Metal , Plaguicidas , Acetilcolinesterasa , Compuestos de Cadmio/química , Técnicas Electroquímicas/métodos , Compuestos Organofosforados , Plata , Tiocolina
15.
Anal Methods ; 14(5): 499-507, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-34981796

RESUMEN

An increasing amount of evidence has proven that serum metabolites can instantly reflect disease states. Therefore, sensitive and reproducible detection of serum metabolites in a high-throughput manner is urgently needed for clinical diagnosis. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a high-throughput platform for metabolite detection, but it is hindered by significant signal fluctuations because of the "sweet spot" effect of organic matrices. Here, by screening two transformation methods and four normalization techniques to reduce the significant signal fluctuations of the DHB matrix, an integrated MALDI-MS data processing approach combined with machine learning methods was established to reveal metabolic biomarkers of lung cancer. In our study, 13 distinctive features with statistically significant differences (p < 0.001) between 34 lung cancer patients and 26 healthy controls were selected as significant potential biomarkers of lung cancer. 6 out of the 13 distinctive features were identified as intact metabolites. Our results demonstrate the potential for clinical application of MALDI-MS in serum metabolomics for biomarker screening in lung cancer.


Asunto(s)
Neoplasias Pulmonares , Metabolómica , Humanos , Neoplasias Pulmonares/diagnóstico , Aprendizaje Automático , Metabolómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
16.
Cancer Res ; 82(2): 248-263, 2022 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-34810201

RESUMEN

Neuroendocrine to nonneuroendocrine plasticity supports small cell lung cancer (SCLC) tumorigenesis and promotes immunogenicity. Approximately 20% to 25% of SCLCs harbor loss-of-function (LOF) NOTCH mutations. Previous studies demonstrated that NOTCH functions as a SCLC tumor suppressor, but can also drive nonneuroendocrine plasticity to support SCLC growth. Given the dual functionality of NOTCH, it is not understood why SCLCs select for LOF NOTCH mutations and how these mutations affect SCLC tumorigenesis. In a CRISPR-based genetically engineered mouse model of SCLC, genetic loss of Notch1 or Notch2 modestly accelerated SCLC tumorigenesis. Interestingly, Notch-mutant SCLCs still formed nonneuroendocrine subpopulations, and these Notch-independent, nonneuroendocrine subpopulations were driven by Runx2-mediated regulation of Rest. Notch2-mutant nonneuroendocrine cells highly express innate immune signaling genes including stimulator of interferon genes (STING) and were sensitive to STING agonists. This work identifies a Notch-independent mechanism to promote nonneuroendocrine plasticity and suggests that therapeutic approaches to activate STING could be selectively beneficial for SCLCs with NOTCH2 mutations. SIGNIFICANCE: A genetically engineered mouse model of NOTCH-mutant SCLC reveals that nonneuroendocrine plasticity persists in the absence of NOTCH, driven by a RUNX2-REST-dependent pathway and innate immune signaling.


Asunto(s)
Plasticidad de la Célula/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor Notch1/metabolismo , Receptor Notch2/metabolismo , Transducción de Señal/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Animales , Sistemas CRISPR-Cas , Carcinogénesis/genética , Carcinogénesis/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Mutación con Pérdida de Función , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Receptor Notch1/genética , Receptor Notch2/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Transfección
17.
Carbohydr Polym ; 266: 118149, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-34044956

RESUMEN

Bletilla striata polysaccharides (BSPs) are effective for anti-inflammatory, detumescence, and radicals scavenging, with important applications in the area of food chain, pharmacy science, and health care. In this study, we comprehensively studied the interplay between the polysaccharides' formation, physicochemical properties, rheological properties, and associated antioxidant activities of BSPs from different extraction methods. The crude polysaccharides obtained from Bletilla striata by using the hot water extraction (BSPs-H), alkali-assisted extraction (BSPs-A), boiling water extraction (BSPs-B), and ultrasonic-assisted extraction (BSPs-U) methods showed different molecular weights, monosaccharide compositions, glycosidic bond compositions, and zeta potentials, but with the same IR spectra characteristic and thermal stability. By the above-mentioned four kinds of extraction methods, the resultant BSPs exhibited various degrees of reticular and lamellar structure. All the BSPs solutions exhibited shear-thinning behavior with the increase of the shear rate. Among these BSPs, BSPs-A exhibited better DPPH and ABTS radical scavenging activities and reducing power, whereas BSPs-H showed better hydroxyl radical scavenging activities.


Asunto(s)
Depuradores de Radicales Libres/química , Polisacáridos/química , Secuencia de Carbohidratos , Depuradores de Radicales Libres/aislamiento & purificación , Peso Molecular , Orchidaceae/química , Tubérculos de la Planta/química , Polisacáridos/aislamiento & purificación , Viscosidad
18.
ACS Appl Mater Interfaces ; 13(13): 15910-15924, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33779136

RESUMEN

Even though compressible carbon aerogels are widely studied for oil/organic solvent recovery, it is challenging to simultaneously achieve excellent mechanical performance and recovery efficiency due to the brittleness of the carbon skeleton. Here a novel strategy is proposed to efficiently fabricate a 3D elastic reduced graphene oxide (RGO)-cross-linked carbon aerogel. Notably, cellulose nanocrystals (CNCs) isolated from plant pulp act as an essential component, and prehydrolysis liquor (PHL), an industrial byproduct in the plant pulping process, serves as the adhesion promoter to achieve enhancement of the strength and flexibility of the carbon aerogel. For the first time, all components (pulp and PHL) of the tree were fully exploited to design a carbon aerogel. The formation of wavy carbon layers with springboard elastic supporting microstructure enables mechanical stretch and shrink as well as avoids interfacial collapse during compression. Benefiting from the unique wavy layer structure and strong interaction, the carbon aerogels are ultralight (4.98 mg cm-3) and exhibit supercompression (undergoing extreme strain of 95%) and superelasticity (about 100% height retention after 500 cycles at a strain of 50%). Particularly, the carbon aerogel can selectively and quickly adsorb various oily contaminants, exhibiting high oil/organic solvents absorption capacity (reaches up to 276 g g-1 for carbon tetrachloride) and good recyclability. Finally, practical applications of the carbon aerogel in oil-cleanup and pollution-remediation devices are exhibited. Hence, this versatile and robust functionalized carbon aerogel has promising potential in oil cleanup and pollution remediation.

19.
ACS Appl Bio Mater ; 3(11): 7483-7491, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-35019490

RESUMEN

Efficient selective separation of oils or organic pollutants from water is important for ecological, environmental conservation and sustainable development. Various absorption methods have emerged; the majority of them still suffer from defects including low removal efficiency, a complicated preparation process, and high cost. Herein, we present a highly porous and mechanical resilient bacterial cellulose (BC) carbon aerogel directly from BC hydrogel via facile directional freeze-drying and high-temperature carbonization. The resultant BC carbon aerogel showed excellent mechanical compressibility (maximal height compression ∼99.5%) and elastic recovery due to the porous structure. Taking advantages of the high thermal stability and superhydrophobicity, the BC carbon aerogel was directly used as a versatile adsorbent for oil/water separation. The result demonstrated that the BC carbon aerogel showed super oil/water separation selectivity with the oil absorption capacity as high as 132-274 g g-1. More importantly, the BC carbon aerogel adsorbent can be reused by a simple absorption/combustion method and still keep high-efficiency oil absorption capacity and excellent superhydrophobicity after 20 absorption/combustion cycles, displaying recyclability and robust stability. In sum, the BC carbon aerogel introduced here is easy to fabricate, ecofriendly, highly scalable, low cost, mechanically robust, and reusable; all of these features make it highly attractive for oil/water separation application.

20.
J Hand Surg Am ; 45(5): 454.e1-454.e8, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31810540

RESUMEN

PURPOSE: Finger pulp resurfacing is a challenging reconstructive problem. This article introduces sensory reconstruction of finger pulp defects using an innervated distally-based neurovascular flap raised from the dorsum of the thumb. METHODS: From May 2015 to May 2017, the innervated distally-based neurovascular flap was used in 36 patients. The mean age at surgery was 37 years (range, 18-61 years). All patients were assessed using the total active motion (TAM) scoring system of the American Society for Surgery of the Hand. The sensitivity of the flap was tested using static 2-point discrimination. RESULTS: Full flap survival was achieved in 35 cases. Partial necrosis at the distal margin of the flap was observed in 1 case. At the final follow-up (mean, 20 months; range, 18-23 months), the mean TAM of the thumb was 206° (range, 188°-238°), including 8 excellent and 28 good results. The mean TAM of fingers was 266° (range, 251°-282°), including 4 excellent and 32 good results. The mean value of static 2-point discrimination was 5 mm (range, 4-7 mm) in the flap, including 31 excellent and 5 good results. CONCLUSIONS: The innervated distally-based neurovascular flap raised from the dorsum of the thumb is a reliable alternative for sensory reconstruction of finger pulp defects. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Asunto(s)
Traumatismos de los Dedos , Procedimientos de Cirugía Plástica , Traumatismos de los Dedos/cirugía , Dedos/cirugía , Humanos , Colgajos Quirúrgicos , Pulgar/lesiones , Pulgar/cirugía , Resultado del Tratamiento
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