Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 95
Filtrar
1.
Artículo en Inglés | MEDLINE | ID: mdl-39302793

RESUMEN

The dissemination of fake news, often fueled by exaggeration, distortion, or misleading statements, significantly jeopardizes public safety and shapes social opinion. Although existing multimodal fake news detection methods focus on multimodal consistency, they occasionally neglect modal heterogeneity, missing the opportunity to unearth the most related determinative information concealed within fake news articles. To address this limitation and extract more decisive information, this article proposes the modality perception learning-based determinative factor discovery (MoPeD) model. MoPeD optimizes the steps of feature extraction, fusion, and aggregation to adaptively discover determinants within both unimodality features and multimodality fusion features for the task of fake news detection. Specifically, to capture comprehensive information, the dual encoding module integrates a modal-consistent contrastive language-image pre-training (CLIP) pretrained encoder with a modal-specific encoder, catering to both explicit and implicit information. Motivated by the prompt strategy, the output features of the dual encoding module are complemented by learnable memory information. To handle modality heterogeneity during fusion, the multilevel cross-modality fusion module is introduced to deeply comprehend the complex implicit meaning within text and image. Finally, for aggregating unimodal and multimodal features, the modality perception learning module gauges the similarity between modalities to dynamically emphasize decisive modality features based on the cross-modal content heterogeneity scores. The experimental evaluations conducted on three public fake news datasets show that the proposed model is superior to other state-of-the-art fake news detection methods.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39231057

RESUMEN

Knowledge distillation (KD) has shown great potential for transferring knowledge from a complex teacher model to a simple student model in which the heavy learning task can be accomplished efficiently and without losing too much prediction accuracy. Recently, many attempts have been made by applying the KD mechanism to graph representation learning models such as graph neural networks (GNNs) to accelerate the model's inference speed via student models. However, many existing KD-based GNNs utilize multilayer perceptron (MLP) as a universal approximator in the student model to imitate the teacher model's process without considering the graph knowledge from the teacher model. In this work, we provide a KD-based framework on multiscaled GNNs, known as graph framelet, and prove that by adequately utilizing the graph knowledge in a multiscaled manner provided by graph framelet decomposition, the student model is capable of adapting both homophilic and heterophilic graphs and has the potential of alleviating the oversquashing issue with a simple yet effective graph surgery. Furthermore, we show how the graph knowledge supplied by the teacher is learned and digested by the student model via both algebra and geometry. Comprehensive experiments show that our proposed model can generate learning accuracy identical to or even surpass the teacher model while maintaining the high speed of inference.

3.
Small ; : e2404402, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963075

RESUMEN

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

4.
Sci Rep ; 14(1): 17753, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085344

RESUMEN

Fairness in machine learning (ML) emerges as a critical concern as AI systems increasingly influence diverse aspects of society, from healthcare decisions to legal judgments. Many studies show evidence of unfair ML outcomes. However, the current body of literature lacks a statistically validated approach that can evaluate the fairness of a deployed ML algorithm against a dataset. A novel evaluation approach is introduced in this research based on k-fold cross-validation and statistical t-tests to assess the fairness of ML algorithms. This approach was exercised across five benchmark datasets using six classical ML algorithms. Considering four fair ML definitions guided by the current literature, our analysis showed that the same dataset generates a fair outcome for one ML algorithm but an unfair result for another. Such an observation reveals complex, context-dependent fairness issues in ML, complicated further by the varied operational mechanisms of the underlying ML models. Our proposed approach enables researchers to check whether deploying any ML algorithms against a protected attribute within datasets is fair. We also discuss the broader implications of the proposed approach, highlighting a notable variability in its fairness outcomes. Our discussion underscores the need for adaptable fairness definitions and the exploration of methods to enhance the fairness of ensemble approaches, aiming to advance fair ML practices and ensure equitable AI deployment across societal sectors.


Asunto(s)
Algoritmos , Aprendizaje Automático , Humanos
5.
ACS Appl Mater Interfaces ; 16(30): 39051-39063, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39028802

RESUMEN

Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a "cold tumor" into a "hot tumor", transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.


Asunto(s)
Carcinoma Hepatocelular , Inmunoterapia , Rayos Infrarrojos , Neoplasias Hepáticas , Fototerapia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Ratones , Humanos , Terapia Fototérmica , Línea Celular Tumoral , Ratones Endogámicos BALB C
6.
IEEE Trans Cybern ; PP2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771679

RESUMEN

Temporal knowledge graphs (TKGs) are receiving increased attention due to their time-dependent properties and the evolving nature of knowledge over time. TKGs typically contain complex geometric structures, such as hierarchical, ring, and chain structures, which can often be mixed together. However, embedding TKGs into Euclidean space, as is typically done with TKG completion (TKGC) models, presents a challenge when dealing with high-dimensional nonlinear data and complex geometric structures. To address this issue, we propose a novel TKGC model called multicurvature adaptive embedding (MADE). MADE models TKGs in multicurvature spaces, including flat Euclidean space (zero curvature), hyperbolic space (negative curvature), and hyperspherical space (positive curvature), to handle multiple geometric structures. We assign different weights to different curvature spaces in a data-driven manner to strengthen the ideal curvature spaces for modeling and weaken the inappropriate ones. Additionally, we introduce the quadruplet distributor (QD) to assist the information interaction in each geometric space. Ultimately, we develop an innovative temporal regularization to enhance the smoothness of timestamp embeddings by strengthening the correlation of neighboring timestamps. Experimental results show that MADE outperforms the existing state-of-the-art TKGC models.

7.
Neural Netw ; 176: 106322, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38653128

RESUMEN

In the realm of long document classification (LDC), previous research has predominantly focused on modeling unimodal texts, overlooking the potential of multi-modal documents incorporating images. To address this gap, we introduce an innovative approach for multi-modal long document classification based on the Hierarchical Prompt and Multi-modal Transformer (HPMT). The proposed HPMT method facilitates multi-modal interactions at both the section and sentence levels, enabling a comprehensive capture of hierarchical structural features and complex multi-modal associations of long documents. Specifically, a Multi-scale Multi-modal Transformer (MsMMT) is tailored to capture the multi-granularity correlations between sentences and images. This is achieved through the incorporation of multi-scale convolutional kernels on sentence features, enhancing the model's ability to discern intricate patterns. Furthermore, to facilitate cross-level information interaction and promote learning of specific features at different levels, we introduce a Hierarchical Prompt (HierPrompt) block. This block incorporates section-level prompts and sentence-level prompts, both derived from a global prompt via distinct projection networks. Extensive experiments are conducted on four challenging multi-modal long document datasets. The results conclusively demonstrate the superiority of our proposed method, showcasing its performance advantages over existing techniques.


Asunto(s)
Redes Neurales de la Computación , Humanos , Procesamiento de Lenguaje Natural , Algoritmos
8.
Artículo en Inglés | MEDLINE | ID: mdl-38446647

RESUMEN

The objective of visual question answering (VQA) is to adequately comprehend a question and identify relevant contents in an image that can provide an answer. Existing approaches in VQA often combine visual and question features directly to create a unified cross-modality representation for answer inference. However, this kind of approach fails to bridge the semantic gap between visual and text modalities, resulting in a lack of alignment in cross-modality semantics and the inability to match key visual content accurately. In this article, we propose a model called the caption bridge-based cross-modality alignment and contrastive learning model (CBAC) to address the issue. The CBAC model aims to reduce the semantic gap between different modalities. It consists of a caption-based cross-modality alignment module and a visual-caption (V-C) contrastive learning module. By utilizing an auxiliary caption that shares the same modality as the question and has closer semantic associations with the visual, we are able to effectively reduce the semantic gap by separately matching the caption with both the question and the visual to generate pre-alignment features for each, which are then used in the subsequent fusion process. We also leverage the fact that V-C pairs exhibit stronger semantic connections compared to question-visual (Q-V) pairs to employ a contrastive learning mechanism on visual and caption pairs to further enhance the semantic alignment capabilities of single-modality encoders. Extensive experiments conducted on three benchmark datasets demonstrate that the proposed model outperforms previous state-of-the-art VQA models. Additionally, ablation experiments confirm the effectiveness of each module in our model. Furthermore, we conduct a qualitative analysis by visualizing the attention matrices to assess the reasoning reliability of the proposed model.

9.
Small ; 20(3): e2306208, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37670543

RESUMEN

Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia , Biomimética , Neoplasias/terapia , Línea Celular Tumoral
10.
Neural Netw ; 169: 1-10, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37852165

RESUMEN

Graph Neural Networks (GNNs) have emerged as a crucial deep learning framework for graph-structured data. However, existing GNNs suffer from the scalability limitation, which hinders their practical implementation in industrial settings. Many scalable GNNs have been proposed to address this limitation. However, they have been proven to act as low-pass graph filters, which discard the valuable middle- and high-frequency information. This paper proposes a novel graph neural network named Adaptive Filtering Graph Neural Networks (AFGNN), which can capture all frequency information on large-scale graphs. AFGNN consists of two stages. The first stage utilizes low-, middle-, and high-pass graph filters to extract comprehensive frequency information without introducing additional parameters. This computation is a one-time task and is pre-computed before training, ensuring its scalability. The second stage incorporates a node-level attention-based feature combination, enabling the generation of customized graph filters for each node, contrary to existing spectral GNNs that employ uniform graph filters for the entire graph. AFGNN is suitable for mini-batch training, and can enhance scalability and efficiently capture all frequency information from large-scale graphs. We evaluate AFGNN by comparing its ability to capture all frequency information with spectral GNNs, and its scalability with scalable GNNs. Experimental results illustrate that AFGNN surpasses both scalable GNNs and spectral GNNs, highlighting its superiority.


Asunto(s)
Redes Neurales de la Computación
11.
Adv Sci (Weinh) ; 10(33): e2303759, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37818787

RESUMEN

Sepsis is a highly heterogeneous syndrome normally characterized by bacterial infection and dysregulated systemic inflammatory response that leads to multiple organ failure and death. Single anti-inflammation or anti-infection treatment exhibits limited survival benefit for severe cases. Here a biodegradable tobramycin-loaded magnesium micromotor (Mg-Tob motor) is successfully developed as a potential hydrogen generator and active antibiotic deliverer for synergistic therapy of sepsis. The peritoneal fluid of septic mouse provides an applicable space for Mg-water reaction. Hydrogen generated sustainably and controllably from the motor interface propels the motion to achieve active drug delivery along with attenuating hyperinflammation. The developed Mg-Tob motor demonstrates efficient protection from anti-inflammatory and antibacterial activity both in vitro and in vivo. Importantly, it prevents multiple organ failure and significantly improves the survival rate up to 87.5% in a high-grade sepsis model with no survival, whereas only about half of mice survive with the individual therapies. This micromotor displays the superior therapeutic effect of synergistic hydrogen-chemical therapy against sepsis, thus holding great promise to be an innovative and translational drug delivery system to treat sepsis or other inflammation-related diseases in the near future.


Asunto(s)
Sepsis , Tobramicina , Animales , Ratones , Insuficiencia Multiorgánica/tratamiento farmacológico , Antibacterianos , Sepsis/tratamiento farmacológico
12.
Acta Pharm Sin B ; 13(9): 3862-3875, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37719374

RESUMEN

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

13.
Nat Commun ; 14(1): 4867, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37567901

RESUMEN

Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor penetration of nanodrugs remains a significant hurdle for effective tumor therapy due to the existing biological barriers of tumoral microenvironment. Inspired by bubble machines, here we report the successful fabrication of biomimetic nanodevices capable of in-situ secreting cell-membrane-derived nanovesicles with smaller sizes under near infrared (NIR) laser irradiation for synergistic photothermal/photodynamic therapy. Porous Au nanocages (AuNC) are loaded with phase transitable perfluorohexane (PFO) and hemoglobin (Hb), followed by oxygen pre-saturation and indocyanine green (ICG) anchored 4T1 tumor cell membrane camouflage. Upon slight laser treatment, the loaded PFO undergoes phase transition due to surface plasmon resonance effect produced by AuNC framework, thus inducing the budding of outer cell membrane coating into small-scale nanovesicles based on the pore size of AuNC. Therefore, the hyperthermia-triggered generation of nanovesicles with smaller size, sufficient oxygen supply and anchored ICG results in enhanced tumor penetration for further self-sufficient oxygen-augmented photodynamic therapy and photothermal therapy. The as-developed biomimetic bubble nanomachines with temperature responsiveness show great promise as a potential nanoplatform for cancer treatment.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Fotoquimioterapia , Biomimética , Hipertermia Inducida/métodos , Fotoquimioterapia/métodos , Fototerapia , Verde de Indocianina/farmacología , Oxígeno , Línea Celular Tumoral
14.
ACS Nano ; 17(17): 16620-16632, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37606341

RESUMEN

Tumor immunotherapy has shown considerable therapeutic potential in the past few years, but the clinical response rate of immunotherapy is less than 20%. Encountering the high heterogeneity of tumors, it will be a general trend to apply combined therapy for cancer treatment. Photodynamic therapy (PDT) transiently kills tumor cells by producing reactive oxygen species (ROS), while residual tumor cells are prone to metastasis, leading to tumor recurrence. In combination with tumor immunotherapy, it is hoped to awaken the host immune system and eradicate residual tumor cells. Herein, cancer cell membrane-coated nanoparticles as a platform to combine PDT, TLR7 agonist, and tumor antigen for the enhancement of tumor therapeutic efficacy are designed. The final biomimetic nanoparticles (CCMV/LTNPs) can specifically kill tumor cells through PDT, while strong host antitumor immune responses are elicited to eliminate residue tumor cells under the help of immune adjuvant and tumor antigen from the cancer cell membrane. In summary, a photoimmunotherapy strategy is designed that synergistically enhances the tumor therapeutic effects by killing tumor cells through PDT and activating host antitumor immune responses through the co-delivery of adjuvant and tumor antigen, which may offer a promising strategy for clinical immunotherapy in the future.


Asunto(s)
Nanopartículas , Receptor Toll-Like 7 , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasia Residual , Inmunoterapia , Adyuvantes Inmunológicos , Membrana Celular , Antígenos de Neoplasias
15.
Artículo en Inglés | MEDLINE | ID: mdl-37459264

RESUMEN

Structured clustering networks, which alleviate the oversmoothing issue by delivering hidden features from autoencoder (AE) to graph convolutional networks (GCNs), involve two shortcomings for the clustering task. For one thing, they used vanilla structure to learn clustering representations without considering feature and structure corruption; for another thing, they exhibit network degradation and vanishing gradient issues after stacking multilayer GCNs. In this article, we propose a clustering method called dual-masked deep structural clustering network (DMDSC) with adaptive bidirectional information delivery (ABID). Specifically, DMDSC enables generative self-supervised learning to mine deeper interstructure and interfeature correlations by simultaneously reconstructing corrupted structures and features. Furthermore, DMDSC develops an ABID module to establish an information transfer channel between each pairwise layer of AE and GCNs to alleviate the oversmoothing and vanishing gradient problems. Numerous experiments on six benchmark datasets have shown that the proposed DMDSC outperforms the most advanced deep clustering algorithms.

16.
ACS Nano ; 17(14): 13826-13839, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37449804

RESUMEN

Interactions between active materials lead to collective behavior and even intelligence beyond the capability of individuals. Such behaviors are prevalent in nature and can be observed in animal colonies, providing these species with diverse capacities for communication and cooperation. In artificial systems, however, collective intelligence systems interacting with biological entities remains unexplored. Herein, we describe black (B)-TiO2@N/Au nanorobots interacting through photocatalytic pure water splitting-induced electrophoresis that exhibit periodic swarming oscillations under programmed near-infrared light. The periodic chemical-electric field generated by the oscillating B-TiO2@N/Au nanorobot swarm leads to local neuron activation in vitro. The field oscillations and neurotransmission from synchronized neurons further trigger the resonance oscillation of neuron populations without synaptic contact (about 2 mm spacing), in different ways from normal neuron oscillation requiring direct contact. We envision that the oscillating nanorobot swarm platforms will shed light on contactless communication of neurons and offer tools to explore interactions between neurons.


Asunto(s)
Neuronas , Titanio , Humanos , Animales , Neuronas/fisiología , Titanio/farmacología , Electricidad
17.
Neural Netw ; 165: 1010-1020, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37467583

RESUMEN

To learn the embedding representation of graph structure data corrupted by noise and outliers, existing graph structure learning networks usually follow the two-step paradigm, i.e., constructing a "good" graph structure and achieving the message passing for signals supported on the learned graph. However, the data corrupted by noise may make the learned graph structure unreliable. In this paper, we propose an adaptive graph convolutional clustering network that alternatively adjusts the graph structure and node representation layer-by-layer with back-propagation. Specifically, we design a Graph Structure Learning layer before each Graph Convolutional layer to learn the sparse graph structure from the node representations, where the graph structure is implicitly determined by the solution to the optimal self-expression problem. This is one of the first works that uses an optimization process as a Graph Network layer, which is obviously different from the function operation in traditional deep learning layers. An efficient iterative optimization algorithm is given to solve the optimal self-expression problem in the Graph Structure Learning layer. Experimental results show that the proposed method can effectively defend the negative effects of inaccurate graph structures. The code is available at https://github.com/HeXiax/SSGNN.


Asunto(s)
Algoritmos , Análisis por Conglomerados
18.
Adv Sci (Weinh) ; 10(27): e2301635, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37518854

RESUMEN

Acute lung injury (ALI) is a frequent and serious complication of sepsis with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis-associated ALI can help develop new therapeutic strategies. Herein, the crucial role of cell-free mitochondrial DNA (cf-mtDNA) in the regulation of alveolar macrophage activation during sepsis-associated ALI is identified. Most importantly, a biocompatible hybrid protein nanomotor (NM) composed of recombinant deoxyribonuclease I (DNase-I) and human serum albumin (HSA) via glutaraldehyde-mediated crosslinking is prepared to obtain an inhalable nanotherapeutic platform targeting pulmonary cf-mtDNA clearance. The synthesized DNase-I/HSA NMs are endowed with self-propulsive capability and demonstrate superior performances in stability, DNA hydrolysis, and biosafety. Pulmonary delivery of DNase-I/HSA NMs effectively eliminates cf-mtDNAs in the lungs, and also improves sepsis survival by attenuating pulmonary inflammation and lung injury. Therefore, pulmonary cf-mtDNA clearance strategy using DNase-I/HSA NMs is considered to be an attractive approach for sepsis-associated ALI.


Asunto(s)
Lesión Pulmonar Aguda , Sepsis , Humanos , ADN Mitocondrial/metabolismo , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/tratamiento farmacológico , Pulmón/metabolismo , Sepsis/complicaciones , Desoxirribonucleasas/metabolismo , Desoxirribonucleasas/uso terapéutico
19.
Exploration (Beijing) ; 3(2): 20220147, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37324036

RESUMEN

The importance of mechanical signals in regulating the fate of macrophages is gaining increased attention recently. However, the recently used mechanical signals normally rely on the physical characteristics of matrix with non-specificity and instability or mechanical loading devices with uncontrollability and complexity. Herein, we demonstrate the successful fabrication of self-assembled microrobots (SMRs) based on magnetic nanoparticles as local mechanical signal generators for precise macrophage polarization. Under a rotating magnetic field (RMF), the propulsion of SMRs occurs due to the elastic deformation via magnetic force and hydrodynamics. SMRs perform wireless navigation toward the targeted macrophage in a controllable manner and subsequently rotate around the cell for mechanical signal generation. Macrophages are eventually polarized from M0 to anti-inflammatory related M2 phenotypes by blocking the Piezo1-activating protein-1 (AP-1)-CCL2 signaling pathway. The as-developed microrobot system provides a new platform of mechanical signal loading for macrophage polarization, which holds great potential for precise regulation of cell fate.

20.
Adv Sci (Weinh) ; 10(25): e2300540, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37382399

RESUMEN

An efficient and cost-effective therapeutic vaccine is highly desirable for the prevention and treatment of cancer, which helps to strengthen the immune system and activate the T cell immune response. However, initiating such an adaptive immune response efficiently remains challenging, especially the deficient antigen presentation by dendritic cells (DCs) in the immunosuppressive tumor microenvironment. Herein, an efficient and dynamic antigen delivery system based on the magnetically actuated OVA-CaCO3 -SPIO robots (OCS-robots) is rationally designed for active immunotherapy. Taking advantage of the unique dynamic features, the developed OCS-robots achieve controllable motion capability under the rotating magnetic field. Specifically, with the active motion, the acid-responsiveness of OCS-robots is beneficial for the tumor acidity attenuating and lysosome escape as well as the subsequent antigen cross-presentation of DCs. Furthermore, the dynamic OCS-robots boost the crosstalk between the DCs and antigens, which displays prominent tumor immunotherapy effect on melanoma through cytotoxic T lymphocytes (CTLs). Such a strategy of dynamic vaccine delivery system enables the active activation of immune system based on the magnetically actuated OCS-robots, which presents a plausible paradigm for incredibly efficient cancer immunotherapy by designing multifunctional and novel robot platforms in the future.


Asunto(s)
Células Dendríticas , Neoplasias , Humanos , Linfocitos T Citotóxicos , Antígenos , Presentación de Antígeno , Neoplasias/terapia , Inmunoterapia Activa , Microambiente Tumoral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA