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1.
Sci Adv ; 10(42): eadp8719, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39423274

RESUMEN

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and ß-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.


Asunto(s)
Colorantes Fluorescentes , Imagen Óptica , Colorantes Fluorescentes/química , Animales , Humanos , Imagen Óptica/métodos , Ratones , beta-Ciclodextrinas/química , Neoplasias/diagnóstico por imagen , Neoplasias/diagnóstico , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/diagnóstico , Carbocianinas/química
2.
Heliyon ; 10(19): e38753, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39430456

RESUMEN

This study performs one-sided lateral unloading- and three-way five-sided force-vertical continuous loading experiments with different intermediate principal stresses (IPS) to investigate the effect of the IPS on deformation, strength, failure modes, and acoustic emission (AE) signals of rock and to elucidate the role of the IPS on the rock strength. The inoculation, occurrence, development, and failure of rockburst as well as the AE evolution characteristics are discussed. The findings indicate that the rockburst ejection includes localized ejections of particles, spalling of rocks into plates, shearing of rocks into fragments, and ejections of rock fragments. The formation mechanism of rockburst involves three progressive processes, i.e., tensile, shear, and tensile-shear composite destruction. The peak stress of sample increases with increasing IPS, while the deformation modulus decreases exponentially as the unloading progresses. The sample properties under true triaxial unloading condition with different IPS can be described by the Mogi-Coulomb criterion. The evolution curves of ringing impact ratio (C H) and cumulative absolute energy can be divided into four stages. The crystal-scale refined model that considers mineral components efficiently simulate the rockburst. The simulated stress-strain (SS) curves of samples are in good agreement with those obtained from laboratory tests.

3.
Chem Soc Rev ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39363873

RESUMEN

Organic luminophores have been widely utilized in cells and in vivo fluorescence imaging but face extreme challenges, including a low signal-to-noise ratio (SNR) and even false signals, due to non-negligible background signals derived from real-time excitation lasers. To overcome these challenges, in the last decade, functionalized organic long-persistent luminophores have gained much attention. Such luminophores could not only overcome the biological toxicity of inorganic long-persistent luminescent materials (metabolic toxicity and leakage risk of inorganic heavy metals), but also continue to emit long-persistent luminescence after removing the excitation source, thus effectively improving imaging quality. More importantly, organic long-persistent luminophores have good structure tailorability for the construction of activable probes, which is favorable for biosensing. Recently, the development of reactive oxygen species (ROS)-mediated long-persistent (ROSLP) luminophores (especially organic small-molecule ROSLP luminophores) is still in the rising stage. Notably, ROSLP luminophores for in vivo imaging have experienced from two-component separated nano-systems to integrated uni-luminophores, which obtained gradually better designability and biocompatibility. In this review, we summarize the progress and challenges of organic long-persistent luminophores, focusing on their development history, long-persistent luminescence working mechanisms, and biomedical applications. We hope that these insights will help scientists further develop functionalized organic long-persistent luminophores for the biomedical field.

4.
Talanta ; 283: 127078, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39467440

RESUMEN

Mature microRNAs play crucial roles in tumorigenesis and progression. However, their potential as cancer biomarkers is limited by the sequence interference of precursor microRNAs and the occurrence of false positive signals mediated by single microRNAs. Herein, we reported a dual mature microRNA-responsive second-order (YES-AND) logic biosensing platform for accurate cancer diagnosis. Specifically, DNA nanocages were conceived as the first stage of "YES" gates, capable of signal transduction through strand displacement reactions, and realizing size-selective discrimination of mature microRNAs and pre-microRNAs. Subsequently, CRISPR/Cas12a system served as the second stage of "AND" gate, wherein dual activators cooperatively triggered trans-cleavage. As a proof-of-concept, this second-order logic biosensing platform was successfully applied to detect non-small cell lung cancer-related mature microRNA in clinical serum, and showed remarkable sensitivity (Lod = 100 pM) and trueness (recovery ≥90 %). Our study represents a significant step forward in the development of intelligent biosensors capable of performing complex computations within pathological networks, and opens up broader possibilities for applications in biological science study and clinic disease diagnosis.

5.
Nat Biomed Eng ; 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39472533

RESUMEN

Low sensitivity, photobleaching, high-power excitation and long acquisition times constrain the utility of afterglow luminescence. Here we report the design and imaging performance of nanoparticles made of electron-rich trianthracene derivatives that, on excitation by room light at ultralow power (58 µW cm-2), emit afterglow luminescence at ~500 times those of commonly used organic afterglow nanoparticles. The nanoparticles' ultrabright afterglow allowed for deep-tissue imaging (up to 6 cm), for ultrafast afterglow imaging (at short acquisition times down to 0.01 s) of naturally behaving mice with negligible photobleaching, even after re-excitation for over 15 cycles, and for the accurate visualization of subcutaneous and orthotopic tumours and of plaque in carotid arteries. We also show that an afterglow nanoparticle that is activated only in the presence of granzyme B allowed for the tracking of granzyme-B activity in the context of therapeutic monitoring. The high sensitivity and negligible photobleaching of the organic afterglow nanoparticles offer advantages for real-time in vivo monitoring of physiopathological processes.

6.
Chem Biomed Imaging ; 2(3): 185-193, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-39474147

RESUMEN

For specific drug research and development, a drug-screening strategy (DSS) plays an indispensable role in the biomedical field. Unfortunately, traditional strategies are complicated and insufficiently accurate due to the widely used single-target screening method. Herein, a simple dual-target-based drug-screening strategy (dt-DSS) is proposed to screen highly effective drugs by fluorescence imaging. As a proof of concept, we utilized a dual-responsive fluorescence probe to screen drugs for diabetic cardiomyopathy (DCM). We first developed and took advantage of a dual-response probe HDB to detect reactive oxygen species (ROS) and mitophagy levels in cellular starvation and high glucose models. Based on this, HDB was utilized to study the effects of different drugs in the mitophagy process caused by the high-glucose cell model for DCM. Combined with Western blotting assays, we found that Drp-1 inhibitors could fundamentally reduce mitophagy caused by the high-glucose cells model. Compared with commercial single-target antioxidant drugs, the drugs with simultaneous antioxidant capacity and Drp-1 inhibition screened by dt-DSS, such as resveratrol and icariin, could treat DCM better. Therefore, HDB as an effective tool could accurately and quickly screen high-potency drugs for DCM. We believe that this work provides an attractive strategy to explore the pathogenesis of diabetic cardiomyopathy and precisely screen for highly effective drugs.

7.
ACS Appl Mater Interfaces ; 16(43): 57995-58005, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39417452

RESUMEN

The abnormal energy metabolism level of a tumor reduces the efficiency of chemotherapy. Metal-organic nanomaterials (MONs) with high drug loading efficiency, easy processes of synthesis, and controlled drug release have shown great potential in metabolic blocking and enhancement of tumor therapy. These metal-organic nanomedicines have been reported to modulate glycolysis or oxidative phosphorylation to provide monotherapy or combined therapies in tumorous treatments. In addition, the encapsulation or coordination of fluorescent dyes into MONs endowed them with the imaging ability of tumor metabolism. Herein, this Perspective summarizes the progress of MONs as therapeutic agents or imaging probes for application during tumor metabolic blocking or imaging, providing solid inspiration for biomedical applications of effective biomaterials. In addition, the current drawbacks of MONs for further biological applications in the future were discussed, giving stimulation of innovation and development in biomedical applications of MONs.


Asunto(s)
Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Animales , Colorantes Fluorescentes/química
8.
Cancer Gene Ther ; 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39468312

RESUMEN

Patients diagnosed with brain glioma have a poor prognosis and limited therapeutic options. LGR4 is overexpressed in brain glioma and involved in the tumorigenesis of many tumors. Baicalein (BAI) is a kind of flavonoid that has exhibited anti-tumor effects in various tumors. Nevertheless, the functions and associations of BAI and LGR4 in brain glioma remain unclear. In this study, Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases were used to perform expression and survival analysis of LGR4 in brain glioma patients. Subsequently, the significance of LGR4-EGFR in brain glioma cells (HS683 and KNS89) and brain glioma animal models was explored by RNA interference and subcutaneous transplantation. Additionally, brain glioma cells were treated with BAI to explore the roles and mechanisms of BAI in brain glioma. The results showed that LGR4 was highly expressed in brain glioma and was related to a poor prognosis. LGR4 knockdown repressed the proliferation and EGFR phosphorylation but induced apoptosis in brain glioma cells. However, these effects were reversed by EGFR overexpression and CBL knockdown. In contrast, both in vitro and in vivo experiments revealed that LGR4 overexpression facilitated brain glioma cell malignant behavior and promoted tumor development, but these effects were rescued by BAI and an EGFR inhibitor. Furthermore, si-LGR4 accelerated EGFR protein degradation, while oe-LGR4 exhibited the opposite effect. Without affecting normal cellular viability, BAI inhibited malignant behavior, interacted with LGR4, and blocked the LGR4-EGFR pathway for brain glioma cells. In conclusion, our data suggested that BAI inhibited brain glioma cell proliferation and induced apoptosis by downregulating the LGR4-EGFR pathway, which provides a novel strategy and potential therapeutic targets to treat brain glioma.

9.
Angew Chem Int Ed Engl ; : e202414327, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39324841

RESUMEN

Immune checkpoints blockade (ICB) therapies have demonstrated remarkable clinical success in treating cancer. However, its objective response rate remains suboptimal because current therapies rely on limited immune checkpoints that failed to cover the multiple immune evasion pathways of cancer. To explore potential ICB strategies, herein, we propose a glycoimmune checkpoint elimination (glycoICE) therapy depending on targeted edition of sialoglycans on tumor cell surface using aptamer-enzyme chimera (ApEC). The ApEC is readily generated via a one-step bioorthogonal procedure, allowing for large-scale and uniform production. The ApEC is able to target and desialylate cancer cells, leading to the elimination of sialoglycan-Siglec axis, which in turn activates immune cells and enhances immunotherapy efficiency. In addition to its remarkable therapeutic efficiency, the ApEC exhibits high tumor selectivity, which helps to avoid side effects caused by indiscriminate desialylation of normal tissues. Furthermore, the ApEC has the potential to be a versatile platform for specifical editing of sialoglycans in different tumor models by adjusting the aptamer sequences targeting associated with specific protein markers. This research not only introduces a novel molecular tool for the effective editing of sialoglycans in complex environments, but also provides valuable insights for advancing DNA-based drugs towards in vivo and clinical applications.

10.
Stem Cells ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283950

RESUMEN

CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors (IDLVs) induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.

11.
Angew Chem Int Ed Engl ; 63(46): e202411840, 2024 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-39115358

RESUMEN

Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O2⋅-/GSH, enabling real-time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide and dual oxidative stress-responsive catechol moieties, facilitates NE-mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685 nm (PA685). Furthermore, oxidation and reduction of catechol groups by O2⋅- and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA745/PA685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug-treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques.


Asunto(s)
Elastasa de Leucocito , Estrés Oxidativo , Técnicas Fotoacústicas , Placa Aterosclerótica , Elastasa de Leucocito/metabolismo , Elastasa de Leucocito/análisis , Animales , Ratones , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/metabolismo , Compuestos de Boro/química , Humanos
12.
Anal Chem ; 96(33): 13447-13454, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39119849

RESUMEN

Small-molecule fluorescent probes have emerged as potential tools for cancer cell imaging-based diagnostic and therapeutic applications, but their limited selectivity and poor imaging contrast hinder their broad applications. To address these problems, we present the design and construction of a novel near-infrared (NIR) biotin-conjugated and viscosity-activatable fluorescent probe, named as QL-VB, for selective recognition and imaging of cancer cells. The designed probe exhibited a NIR emission at 680 nm, with a substantial Stokes shift of 100 nm and remarkably sensitive responses toward viscosity changes in solution. Importantly, QL-VB provided an evidently enhanced signal-to-noise ratio (SNR: 6.2) for the discrimination of cancer cells/normal cells, as compared with the control probe without biotin conjugation (SNR: 1.8). Moreover, we validated the capability of QL-VB for dynamic monitoring of stimulated viscosity changes within cancer cells and employed QL-VB for distinguishing breast cancer tissues from normal tissues in live mice with improved accuracy (SNR: 2.5) in comparison with the control probe (SNR: 1.8). All these findings indicated that the cancer-targeting and viscosity-activatable NIR fluorescent probe not only enables the mechanistic investigations of mitochondrial viscosity alterations within cancer cells but also holds the potential as a robust tool for cancer cell imaging-based applications.


Asunto(s)
Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Viscosidad , Animales , Ratones , Imagen Óptica , Femenino , Rayos Infrarrojos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Línea Celular Tumoral , Biotina/química
13.
Nano Lett ; 24(35): 11002-11011, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39166738

RESUMEN

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.


Asunto(s)
Carcinoma Hepatocelular , Medios de Contraste , Gadolinio , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Humanos , Gadolinio/química , Medios de Contraste/química , Animales , Ratones , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Línea Celular Tumoral
14.
Proc Natl Acad Sci U S A ; 121(33): e2403740121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39102540

RESUMEN

The formation of macrophage-derived foam cells has been recognized as the pathological hallmark of atherosclerotic diseases. However, the pathological evolution dynamics and underlying regulatory mechanisms remain largely unknown. Herein, we introduce a single-particle rotational microrheology method for pathological staging of macrophage foaming and antiatherosclerotic explorations by probing the dynamic changes of lysosomal viscous feature over the pathological evolution progression. The principle of this method involves continuous monitoring of out-of-plane rotation-caused scattering brightness fluctuations of the gold nanorod (AuNR) probe-based microrheometer and subsequent determination of rotational relaxation time to analyze the viscous feature in macrophage lysosomes. With this method, we demonstrated the lysosomal viscous feature as a robust pathological reporter and uncovered three distinct pathological stages underlying the evolution dynamics, which are highly correlated with a pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback loop. We also validated the potential of this positive feedback loop as a promising therapeutic target and revealed the time window-dependent efficacy of NLRP3 inflammasome-targeted drugs against atherosclerotic diseases. To our knowledge, the pathological staging of macrophage foaming and the pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback mechanism have not yet been reported. These findings provide insights into in-depth understanding of evolutionary features and regulatory mechanisms of macrophage foaming, which can benefit the analysis of effective therapeutical drugs as well as the time window of drug treatment against atherosclerotic diseases in preclinical studies.


Asunto(s)
Aterosclerosis , Células Espumosas , Oro , Proteína con Dominio Pirina 3 de la Familia NLR , Aterosclerosis/patología , Animales , Oro/química , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células Espumosas/patología , Células Espumosas/metabolismo , Macrófagos/patología , Macrófagos/metabolismo , Humanos , Lisosomas/metabolismo , Inflamasomas/metabolismo , Nanotubos/química , Reología
15.
Nano Lett ; 24(37): 11335-11348, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39213537

RESUMEN

Inspired by efficient natural biomolecule assembly with precise control on key parameters such as distance, number, orientation, and pattern, the constructions and applications of artificial precise molecule assembly are highly important in many research areas including chemistry, biology, and medicine. DNA origami, a sophisticated DNA nanotechnology with rational design, can offer a predictable, programmable, and addressable nanoscale scaffold for the precise assembly of various kinds of molecules. Herein, we summarize recent progress, particularly in the last three years, in DNA-origami-based precise molecule assembly and their emerging biological applications. We first introduce DNA origami and the progress on DNA-origami-based precise molecule assembly, including assembly of various kinds of molecules (e.g., nucleic acids, proteins, organic molecules, nanoparticles), and precise control of important parameters (e.g., distance, number, orientation, pattern). Their biological applications in sensing, imaging, therapy, bionics, biophysics, and chemical biology are then summarized, and current challenges and opportunities are finally discussed.


Asunto(s)
ADN , Nanotecnología , ADN/química , Nanotecnología/métodos , Humanos , Nanoestructuras/química , Conformación de Ácido Nucleico , Nanopartículas/química , Proteínas/química
16.
Heliyon ; 10(14): e34215, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39092253

RESUMEN

Shezhi Huangling Decoction (SHD) has been proven clinically effective in regulating metabolic and immune homeostasis in the treatment of glioma. The investigation aimed to deconstruct the active constituents and mechanisms of SHD. Effects of SHD on malignant characteristics of HS683 and KNS89 cells have been investigated by CCK-8, clone formation, flow cytometry, and Transwell assays. A mouse xenograft model was established to assess the effect of SHD or SHD + temozolomide (TMZ) in vivo. A total of 461 constituents were found from SHD in UPLC/Q-TOF-MS/MS analysis. Functional enrichment analysis showed that pathway in cancer, proteoglycans in cancer, regulation of epithelial cell proliferation, inflammation/immune, gliogenesis, brain development, cell adhesion, and autophagy could participate in the treatment of SHD. Additionally, 9 hub genes (AKT1, TP53, CTNNB1, STAT3, EGFR, VEGFA, PIK3CA, ERBB2, and HIF1A) were identified as hub genes. Moreover, we found that SHD may greatly reduce the migration and accelerate apoptosis of HS683 and KNS89 cells. Additionally, SHD coordinates TMZ to restrict tumor growth were found in the mice. Our results suggest that the malignant behaviors of glioma cells are suppressed by SHD and the mechanism may be closing on the inhibition of the PI3K/Akt-HIF1A axis. SHD may serve as a synergistic therapeutic choice for TMZ to suppress glioblastoma growth.

17.
ACS Cent Sci ; 10(6): 1201-1210, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38947212

RESUMEN

Coacervates formed by liquid-liquid phase separation emerge as important biomimetic models for studying the dynamic behaviors of membraneless organelles and synchronously motivating the creation of smart architectures with the regulation of cell fate. Despite continuous progress, it remains challenging to balance the trade-offs among structural stability, versatility, and molecular communication for regulation of cell fate and systemic investigation in a complex physiological system. Herein, we present a self-stabilizing and fastener-bound gain-of-function methodology to create a new type of synthetic DNA membraneless organelle (MO) with high stability and controlled bioactivity on the basis of DNA coacervates. Specifically, long single-strand DNA generated by rolling circle amplification (RCA) is selected as the scaffold that assembles into membraneless coacervates via phase separation. Intriguingly, the as-formed DNA MO can recruit RCA byproducts and other components to achieve self-stabilization, nanoscale condensation, and function encoding. As a proof of concept, photoactivatable DNA MO is constructed and successfully employed for time-dependent accumulation and spatiotemporal management of cancer in a mouse model. This study offers new, important insights into synthetic membraneless organelles for the basic understanding and manipulation of important life processes.

18.
Nat Commun ; 15(1): 6349, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39068156

RESUMEN

Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.


Asunto(s)
ADN-(Sitio Apurínico o Apirimidínico) Liasa , Imagen por Resonancia Magnética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Animales , Imagen por Resonancia Magnética/métodos , Femenino , Ratones , Humanos , Línea Celular Tumoral , Medios de Contraste , Neoplasias/radioterapia , Neoplasias/diagnóstico por imagen , Ratones Desnudos , Nanopartículas/química , Ratones Endogámicos BALB C , Radioterapia Guiada por Imagen/métodos
19.
Front Cell Infect Microbiol ; 14: 1359422, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077434

RESUMEN

Background: Aeromonas dhakensis is associated with soft tissue infection, bacteremia and gastroenteritis. Involvement of respiratory system in adults is extremely rare. We report a case of fulminant pneumonia and bacteremia due to A. dhakensis in a patient without underlying diseases. Case presentation: A 26-year-old man became ill suddenly with pneumonia after swimming in a river. Despite intensive support measures in the intensive care unit, he died 13 hours after admission and 4 days after his first symptoms. Autopsy showed abundant Gram-negative bacteria, massive inflammatory cell infiltration, edema, necrosis and hemorrhage in lung tissue. A. dhakensis was isolated from blood culture taken at admission and bronchoalveolar lavage fluid (BALF) after intubation. Moreover, A. dhakensis was also detected in lung tissue by metagenomic next-generation sequencing (mNGS) assay. The infection may have come from river water. Conclusion: In patients who develop a fulminant pneumonia after contacting an aquatic environment, A. dhakensis should be alerted and mNGS may aid in the detection of aquatic pathogens by being more sensitive and specific versus traditional bacterial culture.


Asunto(s)
Aeromonas , Bacteriemia , Líquido del Lavado Bronquioalveolar , Infecciones por Bacterias Gramnegativas , Humanos , Masculino , Adulto , Aeromonas/aislamiento & purificación , Aeromonas/genética , Aeromonas/patogenicidad , Bacteriemia/microbiología , Bacteriemia/diagnóstico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/diagnóstico , Resultado Fatal , Líquido del Lavado Bronquioalveolar/microbiología , Pulmón/patología , Pulmón/microbiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica
20.
ACS Omega ; 9(27): 29471-29477, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39005790

RESUMEN

During production, agricultural products are often susceptible to potential harm caused by residual traces of pesticides. Oxine-copper is a broad spectrum and efficient protective fungicide widely used in the production of fruits and vegetables. The present study was carried out to profile the dissipation behaviors and residues of oxine-copper on cucumber and watermelon using QuEChERS pretreatment and UPLC-MS/MS. Its storage stability and dietary risk assessment were also estimated. The method validation displayed good linearity (R 2 ≥ 0.9980), sensitivity (limits of quantification ≤0.01 mg/kg), and recoveries (75.5-95.8%) with relative standard deviations of 2.27-8.26%. According to first-order kinetics, the half-lives of oxine-copper in cucumber and watermelon were 1.77-2.11 and 3.57-4.68 d, respectively. The terminal residues of oxine-copper in cucumber and watermelon samples were within <0.01-0.264 and <0.01-0.0641 mg/kg, respectively. Based on dietary risk assessment, the estimated long-term dietary risk probability value of oxine-copper in cucumber and watermelon is 64.11%, indicating that long-term consumption of cucumber and watermelon contaminated with oxine-copper would not pose dietary risks to the general population. The results provide scientific guidance for the rational utilization of oxine-copper in field ecosystems of cucumber and watermelon.

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