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BACKGROUND: Excessive pericyte coverage promotes tumor growth, and a downregulation may solve this dilemma. Due to the double-edged sword role of vascular pericytes in tumor microenvironment (TME), indiscriminately decreasing pericyte coverage by imatinib causes poor treatment outcomes. Here, we optimized the use of imatinib in a colorectal cancer (CRC) model in high pericyte-coverage status, and revealed the value of multiparametric magnetic resonance imaging (mpMRI) at 9.4T in monitoring treatment-related changes in pericyte coverage and the TME. METHODS: CRC xenograft models were evaluated by histological vascular characterizations and mpMRI. Mice with the highest pericyte coverage were treated with imatinib or saline; then, vascular characterizations, tumor apoptosis and HIF-1α level were analyzed histologically, and alterations in the expression of Bcl-2/bax pathway were assessed through qPCR. The effects of imatinib were monitored by dynamic contrast-enhanced (DCE)-, diffusion-weighted imaging (DWI)- and amide proton transfer chemical exchange saturation transfer (APT CEST)-MRI at 9.4T. RESULTS: The DCE- parameters provided a good histologic match the tumor vascular characterizations. In the high pericyte coverage status, imatinib exhibited significant tumor growth inhibition, necrosis increase and pericyte coverage downregulation, and these changes were accompanied by increased vessel permeability, decreased microvessel density (MVD), increased tumor apoptosis and altered gene expression of apoptosis-related Bcl-2/bax pathway. Strategically, a 4-day imatinib effectively decreased pericyte coverage and HIF-1α level, and continuous treatment led to a less marked decrease in pericyte coverage and re-elevated HIF-1α level. Correlation analysis confirmed the feasibility of using mpMRI parameters to monitor imatinib treatment, with DCE-derived Ve and Ktrans being most correlated with pericyte coverage, Ve with vessel permeability, AUC with microvessel density (MVD), DWI-derived ADC with tumor apoptosis, and APT CEST-derived MTRasym at 1 µT with HIF-1α. CONCLUSIONS: These results provided an optimized imatinib regimen to achieve decreasing pericyte coverage and HIF-1α level in the high pericyte-coverage CRC model, and offered an ultrahigh-field multiparametric MRI approach for monitoring pericyte coverage and dynamics response of the TME to treatment.
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Apoptose , Neoplasias Colorretais , Subunidade alfa do Fator 1 Induzível por Hipóxia , Mesilato de Imatinib , Imageamento por Ressonância Magnética Multiparamétrica , Pericitos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Animais , Pericitos/metabolismo , Pericitos/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Humanos , Camundongos Nus , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The development of peptide-based hydrogels characterized by both high biostability and potent antimicrobial activity, aimed at combating multidrug-resistant bacterial infections and providing scaffolds for cell cultures, continues to pose a significant challenge. The susceptibility of antimicrobial peptides (AMPs) to degradation by cations, serum, and proteases restricted their applications in clinical environments. In this study, we designed a peptide sequence (termed D-IK1) entirely consisting of D-amino acids, an enantiomer of a previously reported AMP IK1. Our results demonstrated remarkably improved antibacterial and anticancer activities of D-IK1 as compared to IK1. D-IK1 self-assembled into hydrogels that effectively inhibited bacterial and cancer cell growth by the controlled and sustained release of D-IK1. Importantly, D-IK1 was extremely stable in salt solutions and resisted serum and protease degradation. In addition, the D-IK1 hydrogel fostered cell adhesion and proliferation, proving its viability as a 3D scaffold for cell culture applications. Our research presents a versatile, highly stable antibacterial hydrogel scaffold with potential widespread applications in cell culture, wound healing, and the eradication of multidrug-resistant bacterial infections.
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Organic Raman probes, including polymers and small molecules, have attracted great attention in biomedical imaging owing to their excellent biocompatibility. However, the development of organic Raman probes is usually hindered by a mismatch between their absorption spectra and wavelength-fixed excitation, which makes it difficult to achieve resonance excitation necessary to obtain strong Raman signals. Herein, we introduce a covalent organic framework (COF) into the fine absorption spectrum regulation of organic Raman probes, resulting in their significant Raman signal enhancement. In representative examples, a polymer poly(diketopyrrolopyrrole-p-phenylenediamine) (DPP-PD) and a small molecule azobenzene are transformed into the corresponding COF-structured Raman probes. Their absorption peaks show an accurate match of less than 5 nm with the NIR excitation. As such, the COF-structured Raman probes acquire highly sensitive bioimaging capabilities compared to their precursors with negligible signals. By further mechanism studies, we discover that the crystallinity and size of COFs directly affect the π-conjugation degree of Raman probes, thus changing their bandgaps and absorption spectra. Our study offers a universal and flexible method for improving the signal performance of organic Raman probes without changing their structural units, making it more convenient to obtain the highly sensitive organic Raman probes for in vivo bioimaging.
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Análise Espectral Raman , Análise Espectral Raman/métodos , Animais , Humanos , Camundongos , Compostos Azo/química , Estruturas Metalorgânicas/química , Polímeros/química , Estrutura Molecular , Fenilenodiaminas/químicaRESUMO
The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.
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Hidrogéis , Proteínas de Membrana , Microambiente Tumoral , Animais , Hidrogéis/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Imunoterapia/métodos , Camundongos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/terapia , Óxido Nítrico , Humanos , Feminino , Apoptose/efeitos dos fármacosRESUMO
The activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS-STING pathway activation, macrophage-selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer- or lipid-based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage-selective uptake and programmable activation of the cGAS-STING pathway through precise self-assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage-selective uptake, endosomal escape, and cytosolic release of the cGAS-recognizing DNA segment, leading to robust activation of the cGAS-STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS-STING activation.
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Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface-modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over-expressed in atherosclerotic conditions. This paper reviews recent research (2018-present) advances in various ligand-modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.
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OBJECTIVES: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. METHODS: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. RESULTS: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. CONCLUSION: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. CLINICAL RELEVANCE STATEMENT: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. KEY POINTS: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.
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A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor-acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of "Visualized Drug Delivery Systems". Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.
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We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.
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Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/terapia , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Masculino , Criança , Feminino , Adolescente , Glioma Pontino Intrínseco Difuso/terapia , Pré-Escolar , Resultado do Tratamento , Imageamento por Ressonância Magnética , Lactente , Estudos Retrospectivos , Glioma/terapia , Glioma/patologia , Glioma/diagnóstico por imagem , Glioma/mortalidadeRESUMO
BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.
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Leucemia Mieloide Aguda , Nomogramas , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Área Sob a Curva , Leucemia Mieloide Aguda/diagnóstico por imagemRESUMO
Detection of progression is of great importance to breast cancer treatment and can benefit patients. Limited by current detection technologies and biomarkers, early breast cancer progression diagnosis remains challenging. Researchers have found blood extracellular vesicles (EVs)-derived integrin α6ß4 directly facilitate progression in breast cancer, enabling cancer detection. However, EVs size and heterogeneity hinder protein detection, masked by abundant background EVs. Hence, novel tools for efficient detection of EVs with high selectivity and low interference are significantly desired. Here, a new silver-coated gold nanorods SERS probe, termed as Au@Ag@IDA-B/4MSTP, based on DNA aptamer was established for the detection of integrin α6ß4 derived from EVs. Validation of the Au@Ag@IDA-B/4MSTP probes using cell-culture-derived EVs revealed a LOD of 23 particles/µL for EVs detection. This tool was further confirmed to mimic the real state of cancer with subcutaneous tumor model and lung metastasis model in mice. With 10 µL of blood plasma and simple Raman analysis process, the test achieved 85.7 % sensitivity and 83.3 % specificity. Moreover, our method achieves a simplified approach that expedites the detection process. These results demonstrate the good detection performance of Au@Ag@IDA-B/4MSTP probes for EVs integrin α6ß4, and suggest that this non-invasive approach could be a promising tool for early detection of breast cancer progression.
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Neoplasias da Mama , Vesículas Extracelulares , Ouro , Integrina alfa6beta4 , Análise Espectral Raman , Análise Espectral Raman/métodos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Animais , Feminino , Ouro/química , Humanos , Camundongos , Integrina alfa6beta4/metabolismo , Nanotubos/química , Prata/química , Aptâmeros de Nucleotídeos/química , Progressão da Doença , Camundongos Endogâmicos BALB C , Propriedades de SuperfícieRESUMO
A life-threatening illness that poses a serious threat to human health is myocardial infarction. It may result in a significant number of myocardial cells dying, dilated left ventricles, dysfunctional heart function, and ultimately cardiac failure. Based on the development of emerging biomaterials and the lack of clinical treatment methods and cardiac donors for myocardial infarction, hydrogels with good compatibility have been gradually applied to the treatment of myocardial infarction. Specifically, based on the three processes of pathophysiology of myocardial infarction, we summarized various types of hydrogels designed for myocardial tissue engineering in recent years, including natural hydrogels, intelligent hydrogels, growth factors, stem cells, and microRNA-loaded hydrogels. In addition, we also describe the heart patch and preparation techniques that promote the repair of MI heart function. Although most of these hydrogels are still in the preclinical research stage and lack of clinical trials, they have great potential for further application in the future. It is expected that this review will improve our knowledge of and offer fresh approaches to treating myocardial infarction.
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BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.
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Neoplasias do Colo , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Animais , Humanos , Camundongos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
Arsenic pollution is a challenging environmental issue caused by arsenic-bearing wastes from nonferrous metallurgy. Oxidative precipitation via introducing O2 into an ionic Fe(II)-As(V) solution is an advanced method for arsenic immobilization. However, the underlying mechanism is still not well understood. This study proposed a mechanism for scorodite formation by oxidative precipitation, and its thermodynamics were calculated using Gaussian software. Scorodite formation was divided into three stages: precursor formation (3-90 min), oxidative conversion (90-270 min) and crystallization (270-720 min) from the variation in precipitates and solution characterization and parameters such as initial pH, arsenic concentration, and ferrous dosage. In the scorodite formation mechanism, the precursors originate from the coordination polymerization of aqueous Fe(H2O)62+ and H2AsO4-, which contributes to the oxidative conversion of coordinated polymers ([Fe(H2O)4(H2O)]nn+) to basic Fe(H2O)2AsO4 until regular octahedral crystals are formed via nucleation and growth during crystallization. The ΔrGmθ for polymerization varied from -491.96 kJ mol-1 to -33.30 kJ mol-1, and the ΔrGmθ of oxidative conversion changed from -982.16 kJ mol-1 to -224.82 kJ mol-1, demonstrating the feasibility in scorodite formation. This research is significant for understanding scorodite formation in As(V) solutions. It can provide schemes for controlling and modifying the conditions of arsenic-bearing waste immobilization in the laboratories and industries.
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Arsênio , Precipitação Química , Oxirredução , Termodinâmica , Arsênio/química , Arsênio/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
Myocardial infarction (MI) and its associated poor prognosis pose significant risks to human health. Nanomaterials hold great potential for the treatment of MI due to their targeted and controlled release properties, particularly biomimetic nanomaterials. The utilization of biomimetic strategies based on extracellular vesicles (EVs) and cell membranes will serve as the guiding principle for the development of nanomaterial therapy in the future. In this review, we present an overview of research progress on various exosomes derived from mesenchymal stem cells, cardiomyocytes, or induced pluripotent stem cells in the context of myocardial infarction (MI) therapy. These exosomes, utilized as cell-free therapies, have demonstrated the ability to enhance the efficacy of reducing the size of the infarcted area and preventing ischaemic reperfusion through mechanisms such as oxidative stress reduction, polarization modulation, fibrosis inhibition, and angiogenesis promotion. Moreover, EVs can exert cardioprotective effects by encapsulating therapeutic agents and can be engineered to specifically target the infarcted myocardium. Furthermore, we discuss the use of cell membranes derived from erythrocytes, stem cells, immune cells and platelets to encapsulate nanomaterials. This approach allows the nanomaterials to camouflage themselves as endogenous substances targeting the region affected by MI, thereby minimizing toxicity and improving biocompatibility. In conclusion, biomimetic nano-delivery systems hold promise as a potentially beneficial technology for MI treatment. This review serves as a valuable reference for the application of biomimetic nanomaterials in MI therapy and aims to expedite the translation of NPs-based MI therapeutic strategies into practical clinical applications.
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STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field of cancer immunotherapy, owing to their excellent capacity to activate the innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration of the strategies employed to develop effective formulations for STING agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements in delivery systems based on lipids, natural/synthetic polymers, and proteins for STING agonists are summarized. The preparation methodologies of nanoprecipitation, self-assembly, and hydrogel, along with their advantages and disadvantages, are also discussed. Furthermore, the challenges and opportunities in developing next-generation STING agonist delivery systems are elaborated. This review aims to serve as a reference for researchers in designing novel and effective STING agonist delivery systems for cancer immunotherapy.
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Children with prosopagnosia, also known as face blindness, struggle to recognize the faces of acquaintances, which can have a negative impact on their social interactions and overall functioning. This paper reviews existing research on interventions for children with prosopagnosia, including compensatory and remedial strategies, and provides a summary and comparison of their effectiveness. However, despite the availability of these interventions, their effectiveness remains limited and constrained by various factors. The lack of a widely accepted treatment for children with prosopagnosia emphasizes the need for further research to improve intervention strategies. Last, three future research directions were proposed to improve interventions for prosopagnosia, including ecological approaches, the social challenges faced by children, and new potential intervention methods.
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Light field (LF) cameras suffer from a fundamental trade-off between spatial and angular resolutions. Additionally, due to the significant amount of data that needs to be recorded, the Lytro ILLUM, a modern LF camera, can only capture three frames per second. In this paper, we consider space-time super-resolution (SR) for LF videos, aiming at generating high-resolution and high-frame-rate LF videos from low-resolution and low-frame-rate observations. Extending existing space-time video SR methods to this task directly will meet two key challenges: 1) how to re-organize sub-aperture images (SAIs) efficiently and effectively given highly redundant LF videos, and 2) how to aggregate complementary information between multiple SAIs and frames considering the coherence in LF videos. To address the above challenges, we propose a novel framework for space-time super-resolving LF videos for the first time. First, we propose a novel Multi-Scale Dilated SAI Re-organization strategy for re-organizing SAIs into auxiliary view stacks with decreasing resolution as the Chebyshev distance in the angular dimension increases. In particular, the auxiliary view stack with original resolution preserves essential visual details, while the down-scaled view stacks capture long-range contextual information. Second, we propose the Multi-Scale Aggregated Feature extractor and the Angular-Assisted Feature Interpolation module to utilize and aggregate information from the spatial, angular, and temporal dimensions in LF videos. The former aggregates similar contents from different SAIs and frames for subsequent reconstruction in a disparity-free manner at the feature level, whereas the latter interpolates intermediate frames temporally by implicitly aggregating geometric information. Compared to other potential approaches, experimental results demonstrate that the reconstructed LF videos generated by our framework achieve higher reconstruction quality and better preserve the LF parallax structure and temporal consistency. The implementation code is available at https://github.com/zeyuxiao1997/LFSTVSR.