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1.
bioRxiv ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38854037

RESUMEN

Next-Generation Sequencing (NGS) catalyzed breakthroughs across various scientific domains. Illumina's sequencing by synthesis method has long been essential for NGS but emerging technologies like Element Biosciences' sequencing by avidity (AVITI) represent a novel approach. It has been reported that AVITI offers improved signal-to-noise ratios and cost reductions. However, the method relies on rolling circle amplification which can be impacted by polymer size, raising questions about its efficacy sequencing small RNAs (sRNA) molecules including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and others that are crucial regulators of gene expression and involved in various biological processes. In addition, capturing capped small RNAs (csRNA-seq) has emerged as a powerful method to map active or "nascent" RNA polymerase II transcription initiation in tissues and clinical samples. Here, we report a new protocol for seamlessly sequencing short DNA fragments on the AVITI and demonstrate that AVITI and Illumina sequencing technologies equivalently capture human, cattle (Bos taurus) and the bison (Bison bison) sRNA or csRNA sequencing libraries, augmenting the confidence in both approaches. Additionally, analysis of generated nascent transcription start sites (TSSs) data for cattle and bison revealed inaccuracies in their current genome annotations and highlighted the possibility and need to translate small RNA sequencing methodologies to livestock. Our accelerated and optimized protocol therefore bridges the advantages of AVITI sequencing and critical methods that rely on sequencing short DNA fragments.

2.
ACS Appl Mater Interfaces ; 16(12): 15372-15382, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38494605

RESUMEN

Electromagnetic interference (EMI) shielding and infrared stealth technologies are essential for military and civilian applications. However, it remains a significant challenge to integrate various functions efficiently into a material efficiently. Herein, a minimalist strategy to fabricate multifunctional phase change organohydrogels (PCOHs) was proposed, which were fabricated from polyacrylamide (PAM) organohydrogels, MXene/PEDOT:PSS hybrid fillers, and sodium sulfate decahydrate (Na2SO4·10H2O, SSD) via one-step photoinitiation strategies. PCOHs with a high enthalpy value (130.7 J/g) and encapsulation rate (98%) could adjust the temperature by triggering a phase change of SSD, which can hide infrared radiation to achieve medium-low temperature infrared stealth. In addition, the PCOH-based sensor has good strain sensing ability due to the incorporation of MXene/PEDOT:PSS and can precisely monitor human movement. Remarkably, benefiting from the electron conduction of the three-dimensional conductive network and the ion conduction of the hydrogel, the EMI shielding efficiency (k) of PCOHs can reach 99.99% even the filler content as low as 1.8 wt %. Additionally, EMI shielding, infrared stealth, and sensing-integrated PCOHs can be adhered to arbitrary targets due to their excellent flexibility and adaptability. This work offers a promising pathway for fabricating multifunctional phase change materials, which show great application prospects in military and civilian fields.

3.
ACS Nano ; 18(5): 4056-4067, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38270089

RESUMEN

Peptide-based vaccines have been widely investigated in cancer immunotherapy. Despite their high specificity, safety, and low production cost, these vaccines have shown limited success in clinical studies, owing to their poor immunogenicity. Extensive efforts have been devoted to increasing the immunogenicity of peptide vaccines by mixing peptides with adjuvants and/or promoting their delivery to tumor-draining lymph nodes (TdLNs) for better antigen presentation by and maturation of dendritic cells. Among these efforts, the exploration of various nanoparticles has been at the forefront of the rational design and construction of peptide-based vaccines. Here, we present a nanovaccine platform that is built on a self-assembled RNA origami (RNA-OG) nanostructure. As previously reported, this RNA-OG nanostructure is a potent toll-like receptor (TLR)3 agonist. In addition, due to its robust synthesis and versatility in modification, RNA-OG could be readily linked to peptides of interest. Thus, these RNA-OG nanostructures function as adjuvanted nanocarriers to construct RNA-OG-peptide nanovaccines that are uniform in size, consistent in peptide loading, and highly stable. Here, we demonstrate that the assembled RNA-OG-peptide nanovaccines induced dendritic cell maturation, reduced tumor-mediated immunosuppression, and mobilized tumor-specific CD8+ T cell responses at the tumor site. Together, these actions led to the elicitation of an effective antitumor immunity that increased the survival of tumor-bearing mice. The combination of RNA-OG-based nanovaccines with the α-PD-1 immune checkpoint blockade further enhanced the immunity. Hence, our RNA-OG nanostructures represent a robust, simple, and highly effective platform to empower peptide-based vaccines for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Animales , Ratones , Nanovacunas , ARN , Inmunoterapia , Adyuvantes Inmunológicos , Neoplasias/tratamiento farmacológico , Nanopartículas/química , Péptidos/uso terapéutico , Ratones Endogámicos C57BL
4.
ACS Appl Mater Interfaces ; 16(2): 2319-2329, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38174695

RESUMEN

Sodium-ion batteries (SIBs) are becoming an alternative option for large-scale energy storage systems owing to their low cost and abundance. The lattice oxygen redox (LOR), which has the potential to increase the reversible capacity of materials, has promoted the development of high-energy cathode materials in SIBs. However, the utilization of oxygen anion redox reactions usually results in harmful lattice oxygen release, which hastens structural deformation and declines electrochemical performance, severely hindering their practical application. Herein, a ribbon-ordered superstructured P3-type Na0.6Li0.2Mn0.8O2 (NLMO) cathode with a uniform Al2O3 coating through atomic layer deposition (ALD) was synthesized. The cycling stability and rate capability of the materials were improved by a proper thickness of the Al2O3 layer. Differential electrochemical mass spectrometry (DEMS) results clearly suggest that the Al2O3 coating can inhibit the CO2 release caused by the highly active surface of the NLMO material. Moreover, the results of transmission electron microscopy (TEM) and etching X-ray photoelectron spectroscopy (XPS) show that the Al2O3 coating can effectively prevent electrolyte and electrode side reactions and the dissolution of Mn. This surface engineering strategy sheds light on the way to prolong the cycling stability of anionic redox cathode materials.

5.
J Am Chem Soc ; 145(31): 17112-17124, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37498993

RESUMEN

Ligands targeting nucleic acid-sensing receptors activate the innate immune system and play a critical role in antiviral and antitumoral therapy. However, ligand design for in situ stability, targeted delivery, and predictive immunogenicity is largely hampered by the sophisticated mechanism of the nucleic acid-sensing process. Here, we utilize single-stranded RNA (ssRNA) origami with precise structural designability as nucleic acid sensor-based ligands to achieve improved biostability, organelle-level targeting, and predictive immunogenicity. The natural ssRNAs self-fold into compact nanoparticles with defined shapes and morphologies and exhibit resistance against RNase digestion in vitro and prolonged retention in macrophage endolysosomes. We find that programming the edge length of ssRNA origami can precisely regulate the degree of macrophage activation via a toll-like receptor-dependent pathway. Further, we demonstrate that the ssRNA origami-based ligand elicits an anti-tumoral immune response of macrophages and neutrophils in the tumor microenvironment and retards tumor growth in the mouse pancreatic tumor model. Our ssRNA origami strategy utilizes structured RNA ligands to achieve predictive immune activation, providing a new solution for nucleic acid sensor-based ligand design and biomedical applications.


Asunto(s)
ARN , Receptor Toll-Like 7 , Animales , Ratones , Ligandos , ARN/metabolismo , Macrófagos/metabolismo , Inmunidad Innata
6.
Nano Lett ; 23(15): 7188-7196, 2023 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-37499095

RESUMEN

The integration of functional modules at the molecular level into RNA nanostructures holds great potential for expanding their applications. However, the quantitative integration of nucleoside analogue molecules into RNA nanostructures and their impact on the structure and function of RNA nanostructures remain largely unexplored. Here, we report a transcription-based approach to controllably integrate multiple nucleoside analogues into a 2000 nucleotide (nt) single-stranded RNA (ssRNA) origami nanostructure. The resulting integrated ssRNA origami preserves the morphology and biostability of the original ssRNA origami. Moreover, the integration of nucleoside analogues introduced new biomedical functions to ssRNA origamis, including innate immune recognition and regulation after the precise integration of epigenetic nucleoside analogues and synergistic effects on tumor cell killing after integration of therapeutic nucleoside analogues. This study provides a promising approach for the quantitative integration of functional nucleoside analogues into RNA nanostructures at the molecular level, thereby offering valuable insights for the development of multifunctional ssRNA origamis.


Asunto(s)
Nanoestructuras , Nanotecnología , Nanotecnología/métodos , Nucleósidos/farmacología , Nanoestructuras/química , ARN/química , Epigénesis Genética , Conformación de Ácido Nucleico
7.
J Am Chem Soc ; 145(25): 13858-13868, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37329284

RESUMEN

Molecular tessellation research aims to elucidate the underlying principles that govern intricate patterns in nature and to leverage these principles to create precise and ordered structures across multiple scales, thereby facilitating the emergence of novel functionalities. DNA origami nanostructures are excellent building blocks for constructing tessellation patterns. However, the size and complexity of DNA origami tessellation systems are currently limited by several unexplored factors relevant to the accuracy of essential design parameters, the applicability of design strategies, and the compatibility between different tiles. Here, we present a general method for creating DNA origami tiles that grow into tessellation patterns with micrometer-scale order and nanometer-scale precision. Interhelical distance (D) was identified as a critical design parameter determining tile conformation and tessellation outcome. Finely tuned D facilitated the accurate geometric design of monomer tiles with minimized curvature and improved tessellation capability, enabling the formation of single-crystalline lattices ranging from tens to hundreds of square micrometers. The general applicability of the design method was demonstrated by 9 tile geometries, 15 unique tile designs, and 12 tessellation patterns covering Platonic, Laves, and Archimedean tilings. Particularly, we took two strategies to increase the complexity of DNA origami tessellation, including reducing the symmetry of monomer tiles and coassembling tiles of different geometries. Both yielded various tiling patterns that rivaled Platonic tilings in size and quality, indicating the robustness of the optimized tessellation system. This study will promote DNA-templated, programmable molecular and material patterning and open up new opportunities for applications in metamaterial engineering, nanoelectronics, and nanolithography.


Asunto(s)
ADN , Nanoestructuras , ADN/química , Nanoestructuras/química , Conformación de Ácido Nucleico , Replicación del ADN , Nanotecnología/métodos
8.
Angew Chem Int Ed Engl ; 61(51): e202211200, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-36288100

RESUMEN

Photosynthetic organisms organize discrete light-harvesting complexes into large-scale networks to facilitate efficient light collection and utilization. Inspired by nature, herein, synthetic DNA templates were used to direct the formation of dye aggregates with a cyanine dye, K21, into discrete branched photonic complexes, and two-dimensional (2D) excitonic networks. The DNA templates ranged from four-arm DNA tiles, ≈10 nm in each arm, to 2D wireframe DNA origami nanostructures with different geometries and varying dimensions up to 100×100 nm. These DNA-templated dye aggregates presented strongly coupled spectral features and delocalized exciton characteristics, enabling efficient photon collection and energy transfer. Compared to the discrete branched photonic systems templated on individual DNA tiles, the interconnected excitonic networks showed approximately a 2-fold increase in energy transfer efficiency. This bottom-up assembly strategy paves the way to create 2D excitonic systems with complex geometries and engineered energy pathways.


Asunto(s)
ADN , Nanoestructuras , Transferencia de Energía , ADN/química , Nanoestructuras/química , Replicación del ADN , Óptica y Fotónica
9.
Org Lett ; 24(37): 6789-6793, 2022 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-36094854

RESUMEN

Epicoccanes A-D (1-4) are four novel metabolites of an endophytic fungus Epicoccum nigrum. Their distinct unprecedented structures are hypothesized as oxidative dimers of pyrogallol analogues. Compounds 1 and 2 possess a novel spirobicyclo[3.2.1]octane-6,1'-cyclopentane or -cyclohexane core skeleton. Compound 3 is of a unique cage-like pentacyclic system, which unusually contained three continuous spiro-carbons. Compound 4 is a highly rearranged dimer with five contiguous chiral centers. The absolute structures of 1 and 2 were deduced by electronic circular dichroism (ECD) calculations, and those of 3 and 4 were determined by X-ray crystallography. Compounds 1 and 4 showed potential antiliver fibrosis activity.


Asunto(s)
Ascomicetos , Pirogalol , Ascomicetos/química , Ciclohexanos , Ciclopentanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Octanos , Estrés Oxidativo
10.
Artículo en Inglés | MEDLINE | ID: mdl-35638614

RESUMEN

Photothermoelectric (PTE) conversion can achieve the recovery of low-quality light or heat efficiently. Much effort has been devoted to the exploitation of the inorganic heterogeneous asynchronous (separate) PTE conversion system. Here, a full organic PTE film with a pseudobilayer architecture (PBA) according to the homogeneous synchronous (all-in-one) PTE conversion hypothesis was prepared via successive drop-casting a PEDOT:PSS/helical carbon nanotube (HCNT) mixture and PEDOT:PSS onto a vacuum ultraviolet treated substrate. Our results prove that the heptagon-pentagon pairs embedded in HCNTs promote a denser arrangement of the molecular chains of PEDOT, which enhances the crystallinity and affects the thermoelectric properties. The weak connection and hollow structure of HCNTs inhibit the dissipation of heat, and the zT value of the film reaches over 0.01. The PBA film shows better photothermal conversion performance than a neat PEDOT:PSS film and stably generates a temperature difference of over 25.68 °C without external cooling. A flexible PTE chip demo was manufactured, and the ideal open-circuit voltage (simulated via COMSOL) of that reaches over 1.5 mV under weak NIR stimulation (83.12 mW/cm2), which is the best value reported for an organic all-in-one PTE device, and the real maximum output power reaches 2.55 nW (166.01 mW/cm2). The chip has incredible ultraflexibility, and its inner resistance changes less than 1.42% after 10000 bending cycles and displays ultrahigh stability (similarity >90%) in a continuous periodic output. Our work fills the deficit of homogeneous synchronous PTE research for a PEDOT:PSS composite and is a preliminary attempt in an ultraflexible integrated all-in-one PTE chip design.

11.
Biomacromolecules ; 23(4): 1789-1802, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-35344361

RESUMEN

The massive accumulation of plastic waste has caused a serious negative impact on the human living environment. Replacing traditional petroleum-based polymers with biobased and biodegradable poly(l-lactic acid) (PLLA) is considered an effective way to solve this problem. However, it is still a great challenge to manufacture PLLA-based composites with high thermal conductivity and excellent mechanical properties via tailoring the microstructures of the blend composites. In the present work, a melt extrusion-stretching method is utilized to fabricate biodegradable PLLA/poly(butylene adipate-co-butylene terephthalate)/carbon nanofiber (PLLA/PBAT/CNF) blend composites. It is found that the incorporation of the extensional flow field induces the formation of multioriented microstructures in the composites, including the oriented PLLA molecular chains, elongated PBAT dispersed phase, and oriented CNFs, which synergistically improve the thermal conductivity and mechanical properties of the blend composites. At a CNF content of 10 wt %, the in-plane thermal conductivity, tensile strength, and elongation at break of the blend composite reach 1.53 Wm-1 K-1, 66.8 MPa, and 56.5%, respectively, which increased by 31.9, 73.5, and 874.1% compared with those of the conventionally hot-compressed sample (1.16 Wm-1 K-1, 38.5 MPa, and 5.8%, respectively). The main mechanism for the improved thermal conductivity is that the multioriented structure promotes the formation of a CNF thermal conductive network in the composites. The strengthening mechanism is attributed to the orientation of both PLLA molecular chains and CNFs in the stretching direction, restricting the movement of PLLA molecular segments around CNFs, and the toughening mechanism is due to the transformation of PLLA molecular chains from low-energy gt conformers to high-energy gg conformers induced by extensional flow field. More interestingly, after the extrusion-stretched samples are annealed, the oriented PLLA molecular chains form oriented crystal structures such as extended-chain lamellae, common "Shish-kebabs," and hybrid Shish-kebabs, which further enhance the thermal conductivity and heat resistance of the samples. This work reveals the effects of the orientation of the matrix molecular chains and crystallites on the thermal conductivity and mechanical properties of composites and provides a new way to prepare high-performance PLLA-based composites with high thermal conductivity, excellent mechanical properties, and high heat resistance.


Asunto(s)
Nanofibras , Poliésteres , Humanos , Nanofibras/química , Poliésteres/química , Polímeros/química , Conductividad Térmica
12.
Int J Surg ; 99: 106267, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35202861

RESUMEN

BACKGROUND: Chronic osteomyelitis remains a major challenge for orthopedic surgeons due to its high recurrence rate. Surgeons currently have few tools to estimate the likelihood of individual recurrence. We here aimed to develop a nomogram to better estimate individual recurrence rate after surgical treatment of chronic osteomyelitis in long bones. METHODS: We first retrospectively identified patients as training cohort who had received surgical treatment of chronic osteomyelitis in long bones between January 2010 and January 2016 from four hospitals. Patient demographic, microbiological, clinical, and therapeutic variables were collected and analyzed. Univariate and multivariate analyses were performed successively to identify independently predictive factors for recurrence. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. The nomogram was then internally validated with bootstrap resampling. We then further validated the performance of the established nomogram in validation cohort (data from two distinct institutions). RESULTS: Recurrence was found in 136 of 655 (20.8%) and 52 of 201 patients (25.9%) in training and validation cohorts respectively. We included six independent prognostic factors for recurrence in our prediction model: number of previous recurrences, epiphysial involvement, preoperative serum albumin level, axial length of the infectious lesion, lesion-removal method, and application of a muscular flap. After incorporating these six factors, the nomogram achieved good discrimination, with concordance indexes of 0.82 (95% CI, 0.79-0.85) and 0.80 (95% CI, 0.78-0.83) in predicting recurrence in the training and validation cohorts, respectively. Calibration curves were well fitted for both training and validation cohorts. CONCLUSIONS: Our nomogram achieved good preoperative prediction of recurrence in chronic osteomyelitis of long bones. Using this nomogram, the recurrence risk can be confidently predicted for each patient and treatment plan. After considering and discussing the functional prognosis with patients, physicians can establish a rational therapeutic plan. LEVEL OF EVIDENCE: Prognostic, Level III.


Asunto(s)
Nomogramas , Osteomielitis , Teorema de Bayes , Humanos , Osteomielitis/diagnóstico , Osteomielitis/cirugía , Pronóstico , Estudios Retrospectivos
13.
ACS Appl Mater Interfaces ; 14(4): 6057-6070, 2022 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-35042328

RESUMEN

Multifunctional phase change materials (PCMs) are highly desirable for the thermal management of miniaturized and integrated electronic devices. However, the development of flexible PCMs possessing heat energy storage, shape memory, and adjustable electromagnetic interference (EMI) shielding properties under complex conditions remains a challenge. Herein, the multifunctional PCM composites were prepared by encapsulating poly(ethylene glycol) (PEG) into porous MXene/silver nanowire (AgNW) hybrid sponges by vacuum impregnation. Melamine foams (MFs) were chosen as a template to coat with MXene/AgNW (MA) to construct a continuous electrical/thermal conductive network. The MF@MA/PEG composites showed a high latent heat (141.3 J/g), high dimension retention ratio (96.8%), good electrical conductivity (75.3 S/m), and largely enhanced thermal conductivity (2.6 times of MF/PEG). Moreover, by triggering the phase change of the PEG, the sponges displayed a significant photoinduced shape memory function with a high shape fixation ratio (∼100%) and recovery ratio (∼100%). Interestingly, the EMI shielding effectiveness (SE) can be adjusted from 12.4 to 30.5 dB by a facile compression-recovery process based on shape memory properties. Furthermore, a finite element simulation was conducted to emphasize the advantage of the MF@MA/PEG composites in the thermal management of chips. Such flexible PCM composites with high latent heat storage, light-actuated shape memory, and adjustable EMI shielding functions exhibit great potential as smart thermal management materials in military and aerospace applications.

14.
ACS Appl Mater Interfaces ; 13(7): 8808-8822, 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33565860

RESUMEN

Helical carbon nanotube (HCNT) is a vital member of carbon nanomaterials, but little effort was devoted to explore its unique characteristics and applications during the past few decades. Here, we report an organic thermoelectric composite with an excellent photothermoelectric (PTE) effect by conformally wrapping polypyrrole (PPy) on the intricate surface of HCNTs, which have been confirmed to have remarkable near-infrared (NIR) photothermal conversion capability and ultralow heat transportation characteristics. The results indicate that with the increasing HCNT content, PPy shell thickness reduces and exhibits denser as well as partial orientation, while the inter-ring angle slowly decreases and the bipolaron becomes dominant in carrier composition gradually. Consequently, the Seebeck coefficient increases monotonically, whereas the electrical conductivity remains nearly invariant. The final composite combines the benign thermoelectric properties, excellent photothermal response performance, and the lowest thermal conductivity of the carbon-based thermoelectric composite yet reported (0.064 W m-1 K-1). A single strip NIR light-stimulated adjustable delay switch was designed and fabricated, with the open-circuit voltage and short-circuit current under a 400 mW cm-2 NIR-stimulated approach to 720 µV and 62 nA with the discrepancy of consecutive periodic output signals less than 4.2%, exhibiting incredible stability and reliability and demonstrating the highest output voltage of a single strip among the reported organic PTE composite at room temperature. Our work fills in a gap of HCNT research, which hitherto existed in the PTE and thermoelectric field.

15.
Carbohydr Polym ; 253: 117290, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33278953

RESUMEN

The hybrid networks of cellulose nanocrystals (CNCs) and graphene nanoplatelets (GNPs) were constructed in polyethylene glycol (PEG) through the common solution compounding processing, in which GNPs provided the thermally conductive path while CNCs restricted the leakage of PEG during the phase transition. The results showed that CNCs greatly enhanced the shape stability of the composite phase change materials (PCMs) while thermal conductivity was still maintained at high level. At the contents of 8 wt% (CNCs) and 4 wt% (GNPs), the enthalpy of the composite PCM was 145.5 J/g, which was 88 % of pure PEG, and the thermal conductivity was 2.018±0.067 W/m K about 563.7 % higher than that of pure PEG. Furthermore, the composite PCMs exhibited outstanding light-thermal and electro-thermal conversion capabilities. Furthermore, the composite PCMs could be designed as the temperature stabilizing component exhibiting intelligent adaptive thermal management role, providing stable temperature condition for electronic devices in extreme environment.

16.
J Neurosurg ; 134(6): 1783-1790, 2020 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-32707545

RESUMEN

OBJECTIVE: Differentiating central nervous system (CNS) lymphoma from other intracranial malignancies remains a clinical challenge in surgical neuro-oncology. Advances in clinical fluorescence imaging contrast agents and devices may mitigate this challenge. Aptamers are a class of nanomolecules engineered to bind cellular targets with antibody-like specificity in a fraction of the staining time. Here, the authors determine if immediate ex vivo fluorescence imaging with a lymphoma-specific aptamer can rapidly and specifically diagnose xenografted orthotopic human CNS lymphoma at the time of biopsy. METHODS: The authors synthesized a fluorescent CNS lymphoma-specific aptamer by conjugating a lymphoma-specific aptamer with Alexa Fluor 488 (TD05-488). They modified human U251 glioma cells and Ramos lymphoma cells with a lentivirus for constitutive expression of red fluorescent protein and implanted them intracranially into athymic nude mice. Three to 4 weeks postimplantation, acute slices (biopsies, n = 28) from the xenografts were collected, placed in aptamer solution, and imaged with a Zeiss fluorescence microscope. Three aptamer staining concentrations (0.3, 1.0, and 3.0 µM) and three staining times (5, 10, and 20 minutes) followed by a 1-minute wash were tested. A file of randomly selected images was distributed to neurosurgeons and neuropathologists, and their ability to distinguish CNS lymphoma from negative controls was assessed. RESULTS: The three staining times and concentrations of TD05-488 were tested to determine the diagnostic accuracy of CNS lymphoma within a frozen section time frame. An 11-minute staining protocol with 1.0-µM TD05-488 was most efficient, labeling 77% of positive control lymphoma cells and less than 1% of negative control glioma cells (p < 0.001). This protocol permitted clinicians to positively identify all positive control lymphoma images without misdiagnosing negative control images from astrocytoma and normal brain. CONCLUSIONS: Ex vivo fluorescence imaging is an emerging technique for generating rapid histopathological diagnoses. Ex vivo imaging with a novel aptamer-based fluorescent nanomolecule could provide an intraoperative tumor-specific diagnosis of CNS lymphoma within 11 minutes of biopsy. Neurosurgeons and neuropathologists interpreted images generated with this molecular probe with high sensitivity and specificity. Clinical application of TD05-488 may permit specific intraoperative diagnosis of CNS lymphoma in a fraction of the time required for antibody staining.


Asunto(s)
Neoplasias del Sistema Nervioso Central/patología , Fluoresceínas/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Linfoma/patología , Ácidos Sulfónicos/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Biopsia/métodos , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/diagnóstico , Fluoresceínas/análisis , Colorantes Fluorescentes/análisis , Humanos , Linfoma/diagnóstico , Ratones , Ratones Desnudos , Técnicas de Cultivo de Órganos , Ácidos Sulfónicos/análisis , Factores de Tiempo
17.
ACS Nano ; 14(4): 4727-4740, 2020 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-32275389

RESUMEN

Rapid developments in nucleic acid nanotechnology have enabled the rational design and construction of self-assembling DNA and RNA nanostructures that are highly programmable. We recently developed a replicable single-stranded RNA origami (RNA-OG) technology that allows a long RNA molecule to be programmed to self-assemble into nanostructures of various shapes. Here, we show that such RNA-OG is highly stable in serum/plasma, and we thus exploited its immunostimulatory potential. We demonstrated that the RNA-OG stimulates a potent innate response primarily through a Toll-like receptor 3 (TLR3) pathway. In a murine peritoneal metastatic colon cancer model, intraperitoneally injected RNA-OG induced significant tumor retardation or regression by activating NK- and CD8-dependent antitumor immunity and antagonizing the peritoneal immunosuppressive environment. Unlike polyinosinic/polycytidylic acid (PolyIC), a well-known double-stranded RNA analogue, the RNA-OG treatment did not cause a high level of type-I interferons in the blood nor apparent toxicity upon its systemic administration in the animals. This work establishes the function of RNA-OG as a potent line of TLR3 agonists that are safe and effective for cancer immunotherapy.


Asunto(s)
Inmunoterapia , Nanoestructuras , Animales , Factores Inmunológicos , Ratones , Nanotecnología , Poli I-C
18.
Nanoscale ; 12(6): 4005-4017, 2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32016265

RESUMEN

Organic phase change materials (OPCMs) play a great role in energy management owing to their large phase change enthalpy, but their intrinsic low thermal conductivity (TC) and bad encapsulation severely restrict their applications. To overcome these problems, we developed a novel but feasible method to fabricate a graphene nanoplatelet (GNP) aerogel with compact and oriented stacking in-plane walls and many through-plane bridges via melamine foam (MF) and cellulose nanofiber (CNF) co-mediated assembly of GNPs. After impregnating paraffin wax (PW), the composite PCMs exhibit a high TC of 1.42 W m-1 K-1 at only a GNP content of 4.1 wt%, increasing by 407% compared with pure PW, and simultaneously nearly no reduction of the phase change enthalpy of PW. Meanwhile, this kind of composite PCM can not only show excellent light-to-thermal and electric-to-thermal transition ability, but also be applied in delay switch devices with satisfactory results.

19.
Chem Sci ; 10(35): 8224-8235, 2019 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-31673322

RESUMEN

Polymer dielectric composites have widespread applications in many fields ranging from energy storage, microelectronic devices, and sensors to power driven systems, etc. and attract much attention of researchers. However, it is still challenging to prepare advanced polymer dielectric composites with a high dielectric constant (ε'), low dielectric loss (tan δ) and simultaneously high breakdown strength (E bd). In this work, conductive polypyrrole (PPy) nanoparticles were in situ synthesized in a reaction system containing the common barium titanate (BaTiO3, BT) or hydroxylated BaTiO3 (BTOH) particles, and then the PPy@BT and PPy@BTOH composite particles were incorporated into poly(vinylidene fluoride) (PVDF) to prepare the composites. The morphologies and microstructures of the PPy@BT and PPy@BTOH composite particles and the corresponding PVDF composites were comparatively investigated. The results showed that the PPy@BTOH composite particles had a 'mulberry'-like morphology with a rough surface and the self-assembled structure could be maintained in the PVDF composites, which was apparently different from the PVDF/PPy@BT composites, in which most of the PPy nanoparticles dissociatively dispersed in the PVDF matrix. Electrical conductivity measurements showed that at high particle content (≥20 wt%), the PPy@BTOH composite particles endowed the composites with lower electrical conductivity compared with the PPy@BT composite particles. Dielectric property measurements showed that the 'mulberry'-like PPy@BTOH composite particles endowed the PVDF composites with extremely high ε', ultralow tan δ and high E bd compared with the PVDF/PPy@BT composites with dissociatively dispersed PPy nanoparticles and BaTiO3 particles. The polarization and loss mechanisms of the composites were then proposed based on the morphologies and the microstructures of the composites. This work provides an alternative way to fabricate functional dielectric particles through trace functional groups inducing in situ polymerization of conductive polymers, and these particles can be used to fabricate advanced dielectric composites.

20.
ACS Appl Mater Interfaces ; 11(50): 46851-46863, 2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31773943

RESUMEN

Strong rigidity, low thermal conductivity, and short of multi-driven capabilities of form-stable phase change materials (FSPCMs) have limited their practical utilization. Herein, we report a shape-adaptable FSPCM with the coinstantaneous light/electro-driven shape memory properties and light/electro-to-thermal energy storage performance. The FSPCM is fabricated by incorporating the poly(ethylene glycol) (PEG) into the cellulose nanofiber/graphene nanoplatelet (GNP) hybrid-coated melamine foam (CG@MF). The CG@MF/PEG FSPCMs show a good encapsulation effect, enhanced thermal conductivity, and large melting enthalpy (178.9 J g-1). Due to the high elasticity of MF and the excellent photothermal conversion and electrical conductivity of the GNP network, the CG@MF/PEG FSPCMs exhibit a remarkable light/electro-driven shape memory effect by activating the phase change process of PEG. Meanwhile, the CG@MF/PEG FSPCMs can effectively convert light or electric energy into heat energy and reposit the converted energy during the phase change process. Furthermore, the CG@MF/PEG FSPCMs possess excellent multiresponsive self-adhesion properties. A light-sensitive, shape-adaptable, and thermal-insulating container is further explored. This study provides routes toward the development of multiresponsive shape-adaptable FSPCMs for energy storage applications.

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