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1.
Artículo en Inglés | MEDLINE | ID: mdl-38992320

RESUMEN

There has been enduring debate on how attention alters contrast appearance. Recent research indicates that exogenous attention enhances contrast appearance for low-contrast stimuli but attenuates it for high-contrast stimuli. Similarly, one study has demonstrated that endogenous attention heightens perceived contrast for low-contrast stimuli, yet none have explored its impact on high-contrast stimuli. In this study, we investigated how endogenous attention alters contrast appearance, with a specific focus on high-contrast stimuli. In Experiment 1, we utilized the rapid serial visual presentation (RSVP) paradigm to direct endogenous attention, revealing that contrast appearance was enhanced for both low- and high-contrast stimuli. To eliminate potential influences from the confined attention field in the RSVP paradigm, Experiment 2 adopted the letter identification paradigm, deploying attention across a broader visual field. Results consistently indicated that endogenous attention increased perceived contrast for high-contrast stimuli. Experiment 3 employed equiluminant chromatic letters as stimuli in the letter identification task to eliminate potential interference from contrast adaption, which might have occurred in Experiment 2. Remarkably, the boosting effect of endogenous attention persisted. Combining the results from these experiments, we propose that endogenous attention consistently enhances contrast appearance, irrespective of stimulus contrast levels. This stands in contrast to the effects of exogenous attention, suggesting that mechanisms through which endogenous attention alters contrast appearance may differ from those of exogenous attention.

2.
Int J Biol Macromol ; 276(Pt 1): 133689, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971272

RESUMEN

Benzyl isothiocyanate (BITC) is a naturally active bacteriostatic substance and κ-carrageenan (KC) is a good film-forming substrate. In the present study, a nanoemulsion incorporating BITC was fabricated with a particle size of 224.1 nm and an encapsulation efficiency of 69.2 %. Subsequently, the acquired BITC nanoemulsion (BITC-NE) was incorporated into the KC-based film, and the light transmittance of the prepared composite films was lower than that of the pure KC film. Fourier transform infrared spectroscopy and scanning electron microscopy revealed that BITC-NE was compatible with the KC matrix. BITC-NE incorporation enhanced the tensile strength of the KC-based films by 33.7 %, decreased the elongation at break by 33.8 %, decreased the water vapor permeability by 60.1 %, increased the maximum thermal degradation temperature by 48.8 %, and decreased the oxygen permeability by 42 % (p < 0.05). Furthermore, the composite films showed enhanced antimicrobial activity against Staphylococcus aureus, Salmonella typhimurium, and Pseudomonas fluorescens. The developed KC-based composite films were applied to wrap raw beef, which significantly delayed the increase in total viable count, total volatile base nitrogen content, and thiobarbituric acid reactive substances, and prolonged the shelf-life of the raw beef by up to 10 days. These results indicated that the composite films prepared by incorporating BITC nanoemulsions into KC matrices have great antimicrobial application potential.

3.
Mol Neurobiol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38867110

RESUMEN

Sex and apolipoprotein E (APOE) genotype have been shown to influence the risk and progression of Alzheimer's disease (AD). However, the impact of these factors on the functional connectivity of the entorhinal cortex (ERC) in clinically unpaired older adults (CUOA) with amyloid-ß (Aß +) pathology remains unclear. A total of 1022 cognitively normal older adults with Aß + (603 females and 586 APOE ε4 +) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were included in this study. The 2 × 2 (gender, 2 APOE genotypes) analysis of covariance was performed to compare the demographic information, cognitive performance, and volumetric MRI data among these groups. Voxel-wise comparisons of bilateral ERC functional connectivity (FC) were conducted, and partial correlation analyses were used to explore the associations between cognitive performance and ERC-FC strength. We found that the APOE genotype influenced ERC functional connectivity mainly in the sensorimotor network (SMN). Males exhibited higher ERC-FC in the salience network (SN), while females displayed higher ERC-FC in the default mode network (DMN), executive control network (ECN), and reward network. The interplay of sex and APOE genotype on ERC-FC was observed in the SMN and cerebellar lobe. The ERC-FC was associated with executive function and memory performance in individuals with CUOA-Aß + . Our findings provide evidence of sex-specific ERC functional connectivity compensation mechanism in cognitively normal older adults with Aß + pathology. This study may contribute to a better understanding of the mechanisms underlying the early stages of AD and may help develop personalized interventions in preclinical AD.

4.
Front Psychol ; 15: 1350358, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911956

RESUMEN

Introduction: Affective decision-making is a prominent topic in consumer psychology research, with its core assumption being that consumers tend to purchase brands and commodities they like. However, the reasons behind why we develop emotional responses of liking or disliking toward certain commodities, as well as what the underlying neural mechanisms are, remain largely unknown. Methods: This study utilized the S1-S2 paradigm in an experiment wherein S1 presented 12 types of commodities and S2 displayed 48 distinct colored squares. Participants were instructed to assess whether they "Like" or "Dislike" the commodity in S1, which was colored with the S2 color. Electroencephalogram (EEG) recordings were obtained during the reaction process and subsequently analyzed to examine the components of S2-induced event-related potentials (ERPs). Results: The analysis revealed that S2 elicited a significant N270 in the prefrontal scalp area under both the "Like" and "Dislike" conditions. Interestingly, the amplitude of the N270 was significantly higher during the "Dislike" condition compared to the "Like" condition. Discussion: The N270 component was shown to reflect the conflict in physical attributes between S1 and S2, as well as the conflict between commodity and color. This highlights the potential utility of this component as an objective EEG indicator of consumer commodity color preferences in future marketing research.

5.
Food Chem ; 457: 140106, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38901346

RESUMEN

Pectin (PEC)/polyvinyl alcohol (PVA), plasticizers, and polyaminopropyl biguanide (Pb) (0.125%-1%) were used to prepare the film solution. The results demonstrated significantly enhanced tensile strength and elongation at break of PEC/PVA/Pb 0.25% film than PEC/PVA film. Scanning electron microscopy was carried out to investigate the continuous and dense structure of the PEC/PVA/ Pb0.25% film. FTIR, XPS, and XRD revealed that Pb addition to the PEC/PVA film matrix changed its physicochemical properties by forming new hydrogen and CN bonds. Moreover, the composite films exhibited strong antimicrobial activity against food-borne microorganisms (E. coli and S. aureus), and post-harvest pathogens (P. italicum and F. proliferatum) in vitro. The composite film effectively inhibited P. italicum growth during citrus experiments, while maintaining nutritional components (vitamin C, total flavonoid, and total polyphenol content). Overall, the antimicrobial composite film presented promising applicability in food packaging.

6.
J Agric Food Chem ; 72(22): 12618-12629, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38778776

RESUMEN

Microbial nitrogen fixation presents a viable alternative to chemical fertilizers, yet the limited colonization and specificity of naturally occurring nitrogen-fixing microorganisms present significant challenges to their widespread application. In this study, we identified a nitrogen fixation gene cluster (VNnif) in Vibrio natriegens (VN) and tested its nitrogenase activity through the acetylene reduction assay. We investigated the potential utilization of nitrogenase by incorporating the nitrogenase gene cluster from VN into plant growth-promoting rhizosphere bacteria Pseudomonas protegens CHA0 and enhancing its activity to 48.16 nmol C2H2/mg/h through promoter replacement and cluster rearrangement. The engineered strain CHA0-PVNnif was found to positively impact the growth of Arabidopsis thaliana col-0 and Triticum aestivum L. (wheat). This study expanded the role of plant growth-promoting rhizobacteria (PGPR) and provided a research foundation for enhancing nitrogenase activity.


Asunto(s)
Proteínas Bacterianas , Fijación del Nitrógeno , Nitrogenasa , Vibrio , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/enzimología , Arabidopsis/crecimiento & desarrollo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Familia de Multigenes , Nitrogenasa/metabolismo , Nitrogenasa/genética , Rizosfera , Triticum/microbiología , Triticum/genética , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Vibrio/genética , Vibrio/crecimiento & desarrollo , Vibrio/enzimología
7.
J Colloid Interface Sci ; 669: 816-824, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38749220

RESUMEN

The precise and controllable preparation of carbon nanomaterials under mild conditions poses a great challenge, especially for metal-catalysed multiphase preparation. This work proposes an efficient method that utilizing high-density ultrasound to enhance the liquid-liquid interfacial reaction system. Iron-doped carbon dots (Fe-CDs) are successfully synthesized in such a normal temperature and atmospheric-pressure reaction condition. It is shown that transient cavitation provides a high-temperature and high-pressure microenvironment for the preparation of Fe-CDs. Moreover, the size of the reactant droplets is reduced from 200.0 ± 17.3 µm to 8.1 ± 2.9 µm owing to the acoustic flow and cavitation effects, which increases the specific surface area of the two reacting phases and improves the mass transfer coefficient by more than 252.0 %. As a result, the yield increases by more than an order of magnitude (from 0.7 ± 0.1 % to 11.9 ± 0.2 %) and the Fe doping rate reaches 20.9 %. The photocatalytic oxidation conversion of 1,4-Dihydropyridine (1,4-DHP) using the obtained Fe-CDs is as high as 98.2 %. This research gives a new approach for the efficient and safe production of Fe-CDs, which is promising for industrial applications.

8.
Gels ; 10(5)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38786217

RESUMEN

Fiber-particle-reinforced silica aerogels are widely applied in thermal insulation. Knowing their effective thermal conductivity (ETC) and radiative characteristics under high temperatures is necessary to improve their performance. This article first analyzes the radiation characteristics of silica aerogels doped with opacifier particles and reinforced fibers, and then a universal model is established to predict the ETC. Furthermore, the impacts of different parameters of opacifier particles and reinforced fibers on the thermal insulation performance of silica aerogels are investigated. The results indicate that SiC exhibits comparatively strong absorption characteristics, making it a good alternative for opacifiers to improve thermal insulation performance under high temperatures. For the given type and volume fraction of opacifier particles, there exists an optimal diameter and volume fraction to achieve the best insulation performance of silica aerogel under a certain temperature. Considering that SiO2 fibers exhibit a limited extinction capability and higher conductive thermal conductivity under high temperatures, for fiber-particle-reinforced silica aerogels, it is beneficial for their insulation performance to reduce the fiber volume fraction when the required mechanical properties are satisfied.

9.
Front Cardiovasc Med ; 11: 1363235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38586171

RESUMEN

Primary cardiac angiosarcoma is a rare malignant soft-tissue sarcoma derived from vascular endothelial cells or lymphatic endothelial cells, with a high malignancy, poor prognosis, and a lack of effective medical therapy. This article reports on two patients with primary cardiac angiosarcoma who received first-line treatment with multi-targeted anti-angiogenic agent, anlotinib monotherapy. The treatment rapidly controlled pleural and pericardial effusion, significantly reduced the tumor, improved symptoms, and showed satisfactory recent efficacy. This indicates that anlotinib offers a new first-line treatment option for advanced primary cardiac angiosarcoma.

10.
Mol Cell ; 84(9): 1637-1650.e10, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38604171

RESUMEN

Long interspersed element-1 (LINE-1 or L1) comprises 17% of the human genome, continuously generates genetic variations, and causes disease in certain cases. However, the regulation and function of L1 remain poorly understood. Here, we uncover that L1 can enrich RNA polymerase IIs (RNA Pol IIs), express L1 chimeric transcripts, and create contact domain boundaries in human cells. This impact of L1 is restricted by a nuclear matrix protein scaffold attachment factor B (SAFB) that recognizes transcriptionally active L1s by binding L1 transcripts to inhibit RNA Pol II enrichment. Acute inhibition of RNA Pol II transcription abolishes the domain boundaries associated with L1 chimeric transcripts, indicating a transcription-dependent mechanism. Deleting L1 impairs domain boundary formation, and L1 insertions during evolution have introduced species-specific domain boundaries. Our data show that L1 can create RNA Pol II-enriched regions that alter genome organization and that SAFB regulates L1 and RNA Pol II activity to preserve gene regulation.


Asunto(s)
Elementos de Nucleótido Esparcido Largo , Proteínas de Unión a la Región de Fijación a la Matriz , ARN Polimerasa II , Receptores de Estrógenos , Transcripción Genética , Humanos , ARN Polimerasa II/metabolismo , ARN Polimerasa II/genética , Elementos de Nucleótido Esparcido Largo/genética , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Proteínas Asociadas a Matriz Nuclear/metabolismo , Proteínas Asociadas a Matriz Nuclear/genética , Regulación de la Expresión Génica , Unión Proteica , Células HEK293 , Genoma Humano
11.
Int J Biol Macromol ; 267(Pt 1): 131584, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615856

RESUMEN

Heterocyclic aromatic amines (HAAs) are the main carcinogens produced during thermal processing of protein-rich foods. In this paper, a composite aerogel (TOCNFCa) with a stabilized dual-network structure was prepared via a template for the in-situ synthesis of UiO-66 on cellulose for the adsorption of HAAs in food. The dual-network structure of TOCNFCa provides the composite aerogel with excellent wet strength, maintaining excellent compressive properties. With the in-situ grown UiO-66 content up to 71.89 wt%, the hierarchical porosity endowed TOCNFCa@UiO-66 with the ability to rapidly adsorb HAAs molecules with high capacity (1.44-5.82 µmol/g). Based on excellent thermal stability, adsorption capacity and anti-interference, TOCNFCa@UiO-66 achieved satisfactory recoveries of HAAs in the boiled marinade, which is faster and more economical than the conventional SPE method. Moreover, TOCNFCa@UiO-66 could maintain 84.55 % of the initial adsorption capacity after 5 times of reuse.


Asunto(s)
Aminas , Celulosa , Compuestos Heterocíclicos , Estructuras Metalorgánicas , Nanofibras , Ácidos Ftálicos , Celulosa/química , Adsorción , Aminas/química , Nanofibras/química , Estructuras Metalorgánicas/química , Compuestos Heterocíclicos/química , Geles/química , Porosidad
12.
J Proteome Res ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686625

RESUMEN

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1I1061T) while filtering out any protein interactor identified in the Npc1-/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1I1061T. Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1I1061T. Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux.

13.
Food Chem ; 449: 139225, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38599107

RESUMEN

Heterocyclic aromatic amines (HAAs), arising as chemical derivatives during the high-temperature culinary treatment of proteinaceous comestibles, exhibit notable carcinogenic potential. In this paper, a composite aerogel (AGD-UiO-66) with high-capacity and fast adsorption of HAAs was made with anchoring defective UiO-66 (D-UiO-66) mediated by lauric acid on the backbone of cellulose nanofibers (CNF). AGD-UiO-66 with hierarchical porosity reduced the mass transfer efficiency for the adsorption of HAAs and achieved high adsorption amount (0.84-1.05 µmol/g) and fast adsorption (15 min). The isothermal adsorption model demonstrated that AGD-UiO-66 belonged to a multilayer adsorption mechanism for HAAs. Furthermore, AGD-UiO-66 was successfully used to adsorb 12 HAAs in different food (roasted beef, roasted pork, roasted salmon and marinade) with high recoveries of 94.65%-104.43%. The intrinsic potential of AGD-UiO-66 demonstrated that it could be widely applicable to the adsorption of HAAs in foods.


Asunto(s)
Aminas , Celulosa , Nanocompuestos , Adsorción , Aminas/química , Celulosa/química , Animales , Nanocompuestos/química , Compuestos Heterocíclicos/química , Bovinos , Porcinos , Salmón , Estructuras Metalorgánicas/química , Carne/análisis , Contaminación de Alimentos/análisis , Geles/química
14.
World J Clin Cases ; 12(8): 1422-1429, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38576804

RESUMEN

BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree. The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges, primarily attributable to its morphological similarity to other tumors containing clear cells. CASE SUMMARY: A 22-year-old male, formerly in good health, came in with a two-month duration of persistent cough and production of sputum. Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus, which resulted in complete atelectasis of the left lung. Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor, characterized by clear cell morphology in most of the tumor cells. The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection. Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion, leading to a definitive pathological diagnosis of the clear cell variant of PMEC, staged as T2N0M0. After surgery, the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period. CONCLUSION: This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male. The patient underwent successful left lower lobe sleeve resection. This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy, underscoring the importance of precise diagnosis and personalized treatment strategies.

15.
Polymers (Basel) ; 16(6)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38543445

RESUMEN

Bilayer hydrogel actuators, consisting of an actuating layer and a functional layer, show broad applications in areas such as soft robotics, artificial muscles, drug delivery and tissue engineering due to their inherent flexibility and responses to stimuli. However, to achieve the compatibility of good stimulus responses and high mechanical properties of bilayer hydrogel actuators is still a challenge. Herein, based on the double-network strategy and using the synchronous ultraviolet (UV) polymerization method, an upper critical solution temperature (UCST)-type bilayer hydrogel actuator was prepared, which consisted of a poly(acrylamide-co-acrylic acid)[MC] actuating layer and an agar/poly(N-hydroxyethyl acrylamide-co-methacrylic acid)[AHA] functional layer. The results showed that the tensile stress/strain of the bilayer hydrogel actuator was 1161.21 KPa/222.07%. In addition, the UCST of bilayer hydrogels was ~35 °C, allowing the bilayer hydrogel actuator to be curled into an "◎" shape, which could be unfolded when the temperature was 65 °C, but not at a temperature of 5 °C. Furthermore, hydrogel actuators of three different shapes were designed, namely "butterfly", "cross" and "circle", all of which demonstrated good actuating performances, showing the programmable potential of bilayer hydrogels. Overall, the bilayer hydrogels prepared using double-network and synchronous UV polymerization strategies realized the combination of high mechanical properties with an efficient temperature actuation, which provides a new method for the development of bilayer hydrogel actuators.

16.
Langmuir ; 40(11): 5818-5827, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38447182

RESUMEN

Partially miscible solutions with a lower critical solution temperature have promising applications in the field of physical chemistry. To better guide the utilization of these solutions in practice, we conduct an in-depth study about the phase separation behavior of the solution added with inorganic salts. The addition of the inorganic salts into the solution is found to consequently reduce the phase separation temperature. The variation of concentrations of inorganic salts does not notably affect the mass fraction of the separation. Moreover, the addition of inorganic salts in the solutions at lower mass fractions improves the separation mass fraction, while the addition of inorganic salts decreases the separation mass fraction at the mass fractions above 30%. It sheds light on selecting the proper mass fractions and inorganic salt concentrations. Furthermore, we explore the phase separation behavior of mixed solutions under different inorganic salt additions by means of a high-speed camera. The phase separation behavior under different inorganic salt systems shows a similar trend. However, calcium ions and Fe3+ ions in the solutions can greatly decrease the rate of droplet coalescence and result in an increase in phase separation. For better regulating the solutions with a lower critical solution temperature through inorganic salts, sodium chloride or potassium chloride is recommended with an appropriate concentration.

17.
Mol Carcinog ; 63(6): 1079-1091, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38426809

RESUMEN

This study was to explore the role of ELOVL6 in the development of head and neck squamous cell carcinoma (HNSCC). Considering its previously identified oncogenic role in hepatocellular carcinoma. ELOVL6 gene expression, clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on the data from Gene Expression Omnibus and The Cancer Genome Atlas, with additional bioinformatics analyses performed. Human HNSCC tissue microarray and cell lines were used. The expression of ELOVL6 in HNSCC was detected by quantitative polymerase chain reaction, immunohistochemistry assay, and western blot analysis. The proliferation ability of HNSCC cells, invasion, and apoptosis were evaluated using cell counting kit-8 method, Transwell assay, and flow cytometry, respectively. Based on the data derived from the cancer databases and our HNSCC cell and tissue studies, we found that ELOVL6 was overexpressed in HNSCC. Moreover, ELOVL6 expression level had a positive correlation with clinicopathology of HNSCC. Gene set enrichment analysis showed that ELOVL6 affected the occurrence of HNSCC through WNT signaling pathway. Functional experiments demonstrated that ELOVL6 knockdown inhibited the proliferation and invasion of HNSCC cells while promoting apoptosis. Additionally, compound 3f, an agonist of WNT/ß-catenin signaling pathway, enhances the effect of ELOVL6 on the progression of HNSCC cells. ELOVL6 is upregulated in HNSCC and promotes the development of HNSCC cells by inducing WNT/ß-catenin signaling pathway. ELOVL6 stands a potential target for the treatment of HNSCC and a prognosis indicator of human HNSCC.


Asunto(s)
Apoptosis , Proliferación Celular , Progresión de la Enfermedad , Elongasas de Ácidos Grasos , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Vía de Señalización Wnt , Humanos , Vía de Señalización Wnt/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Proliferación Celular/genética , Elongasas de Ácidos Grasos/genética , Elongasas de Ácidos Grasos/metabolismo , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Movimiento Celular/genética
18.
J Control Release ; 366: 395-409, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184235

RESUMEN

Tumor-associated macrophages (TAMs) play a key role in inducing an immunosuppressive tumor microenvironment (TME) and cancer immune escape. We previously revealed that PDL1 (a key immune checkpoint) was upregulated in TAMs and induced M2 polarization, highlighting PDL1 in TAMs as a promising cancer therapeutic target. In this study, we developed an engineered milk exosome (mExo) system decorated with M2pep (an M2 macrophage binding peptide) and 7D12 (an anti-EGFR nanobody) (7D12-mExo-M2pep-siPDL1) to specifically deliver siPDL1 into M2 TAMs. A series of in vitro and in vivo assays showed that the dually targeted engineered mExos efficiently delivered siPDL1 into M2 TAMs and repolarized them into M1 macrophages, restoring CD8+ T cell immune activity and remodeling TME. Importantly, systemically administered 7D12-mExo-M2pep-siPDL1 showed efficient single-agent antitumor activity, resulting in nearly 90% tumor growth inhibition in a mouse model of orthotopic epidermal growth factor receptor (EGFR) cancer. Collectively, our study indicates that PDL1 is a promising target for TAM-based cancer immunotherapy, and our engineered mExo-based nanomedicine represents a novel tool for specifically targeting M2 TAMs, distinguishing this novel therapeutic method from other TAM-targeting therapies and highlighting its promising clinical potential.


Asunto(s)
Exosomas , Neoplasias , Animales , Ratones , Macrófagos Asociados a Tumores , Leche , Macrófagos , Neoplasias/terapia , Microambiente Tumoral
19.
Adv Sci (Weinh) ; 11(13): e2307613, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38286668

RESUMEN

Cetuximab resistance is a significant challenge in cancer treatment, requiring the development of novel therapeutic strategies. In this study, a series of multivalent rhamnose (Rha)-modified nanobody conjugates are synthesized and their antitumor activities and their potential to overcome cetuximab resistance are investigated. Structure-activity relationship studies reveal that the multivalent conjugate D5, bearing sixteen Rha haptens, elicits the most potent innate fragment crystallizable (Fc) effector immunity in vitro and exhibits an excellent in vivo pharmacokinetics by recruiting endogenous antibodies. Notably, it is found that the optimal conjugate D5 represents a novel entity capable of reversing cetuximab-resistance induced by serine protease (PRSS). Moreover, in a xenograft mouse model, conjugate D5 exhibits significantly improved antitumor efficacy compared to unmodified nanobodies and cetuximab. The findings suggest that Rha-Nanobody (Nb) conjugates hold promise as a novel therapeutic strategy for the treatment of cetuximab-resistant tumors by enhancing the innate Fc effector immunity and enhancing the recruitment of endogenous antibodies to promote cancer cell clearance by innate immune cells.


Asunto(s)
Resistencia a Antineoplásicos , Receptores ErbB , Ramnosa , Anticuerpos de Dominio Único , Animales , Humanos , Ratones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Línea Celular Tumoral , Cetuximab/farmacología , Cetuximab/uso terapéutico , Receptores ErbB/inmunología , Inmunidad Innata , Anticuerpos de Dominio Único/farmacología , Resistencia a Antineoplásicos/inmunología
20.
Artículo en Inglés | MEDLINE | ID: mdl-38178659

RESUMEN

BACKGROUND: Thyroid nodules are common lesions in benign and malignant thyroid diseases. More and more studies have been conducted on the feasibility of artificial intelligence (AI) in the detection, diagnosis, and evaluation of thyroid nodules. The aim of this study was to use bibliometric methods to analyze and predict the hot spots and frontiers of AI in thyroid nodules. METHODS: Articles on the application of artificial intelligence in thyroid nodules were retrieved from the Web of Science core collection database. A website (https://bibliometric.com/), VOSviewer and CiteSpace software were used for bibliometric analyses. The collaboration maps of countries and institutions were analyzed. The cluster and timeline view based on cocitation references and keywords citation bursts visualization map were generated. RESULTS: The study included 601 papers about AI in thyroid nodules. China contributed to more than half (52.41%) of these publications. The cluster view and timeline view of co-citation references were assembled into 9 clusters, "AI", "deep learning", "papillary thyroid carcinoma", "radiomics", "ultrasound image", "biomarkers", "medical image segmentation", "central lymph node metastasis (CLNM)", and "self-organizing auto-encoder". The "AI", "radiomics", "medical image segmentation", "deep learning," and "CLNM", emerging in the last 10 years and continuing until recent years, were included. CONCLUSION: An increasing number of scholars were devoted to this field. The potential future research hotspots include risk factor assessment and CLNM prediction of thyroid carcinoma based on radiomics and deep learning, automatic segmentation based on medical images (especially ultrasound images).

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