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AIMS: Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness. METHODS: We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively. RESULTS: We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory. CONCLUSION: Our findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective.
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Estudios de Factibilidad , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Vigilia , Animales , Estimulación del Nervio Vago/métodos , Estimulación del Nervio Vago/instrumentación , Vigilia/fisiología , Masculino , Estimulación Eléctrica Transcutánea del Nervio/métodos , Estimulación Eléctrica Transcutánea del Nervio/instrumentación , Ratones , Ratones Endogámicos C57BL , Aprendizaje por Laberinto/fisiología , Ansiedad/terapia , Reconocimiento en Psicología/fisiología , Prueba de Campo Abierto , Herpesvirus Suido 1RESUMEN
Protein therapeutics play a critical role in treating a large variety of diseases, ranging from infections to genetic disorders. However, their delivery to target tissues beyond the liver, such as the lungs, remains a great challenge. Here, we report a universally applicable strategy for lung-targeted protein delivery by engineering Lung-Specific Supramolecular Nanoparticles (LSNPs). These nanoparticles are designed through the hierarchical self-assembly of metal-organic polyhedra (MOP), featuring a customized surface chemistry that enables protein encapsulation and specific lung affinity after intravenous administration. Our design of LSNPs not only addresses the hurdles of cell membrane impermeability of protein and nonspecific tissue distribution of protein delivery, but also shows exceptional versatility in delivering various proteins, including those vital for anti-inflammatory and CRISPR-based genome editing to the lung, and across multiple animal species, including mice, rabbits, and dogs. Notably, the delivery of antimicrobial proteins using LSNPs effectively alleviates acute bacterial pneumonia, demonstrating a significant therapeutic potential. Our strategy not only surmounts the obstacles of tissue-specific protein delivery but also paves the way for targeted treatments in genetic disorders and combating antibiotic resistance, offering a versatile solution for precision protein therapy.
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Edición Génica , Pulmón , Nanopartículas , Animales , Edición Génica/métodos , Pulmón/metabolismo , Ratones , Nanopartículas/química , Perros , Conejos , Humanos , Sistemas CRISPR-Cas , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Two-dimensional ferromagnetic/antiferromagnetic (2D-FM/AFM) heterostructures are of great significance to realize the application of spintronic devices such as miniaturization, low power consumption, and high-density information storage. However, traditional mechanical stacking can easily damage the crystal quality or cause chemical contamination residues for 2D materials, which can result in weak interface coupling and difficulty in device regulation. Chemical vapor deposition (CVD) is an effective way to achieve a high-quality heterostructure interface. Herein, high-quality interface 2D-FM/AFM Cr7Te8/MnTe vertical heterostructures were successfully synthesized via a one-pot CVD method. Moreover, the atomic-scale structural scanning transmission electron microscope (STEM) characterization shows that the interface of the vertical heterostructure is clear and flat without an excess interface layer. Compared to the parent Cr7Te8, the coercivity (HC) of the high-quality interface Cr7Te8/MnTe heterostructure is significantly reduced as the thickness of MnTe increases, with a maximum decrease of 74.5% when the thickness of the MnTe nanosheet is around 30 nm. Additionally, the HC of the Cr7Te8/MnTe heterostructure can also be regulated by applying a gate voltage, and the HC increases or decreases with increasing positive or negative gate voltages. Thus, the effective regulation of HC is essential to improving the performance of advanced spintronic devices (e.g., MRAM and magnetic sensors). Our work will provide ideas for spin controlling and device application of 2D-FM/AFM heterostructures.
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Investigations have revealed the presence of microplastics in both soil and groundwater, but the migration characteristics from soil to groundwater remain incompletely understood. In this study, two sampling sections consisting of soil-groundwater-river water were established near Lianxi Bridge and Xilin Bridge along the Jiuxi River in Xiamen. A total of 22 soil samples, 36 groundwater samples, and 18 river water samples were collected. Microplastics were detected in all samples with an abundance range of 392-836 n/kg in soil (mean, 655 ± 177 n/kg), 0.58-2.48 n/L groundwater (mean, 1.23 ± 0.42 n/L), and 0.38-1.80 n/L in river water (mean, 0.86 ± 0.41 n/L). Flakes predominantly constituted the shape of microplastics found in soil, while fibers dominated those present in water. Black, yellow, and red were the dominant color types. Polyamide (PA) and polyethylene (PE) were the main components of microplastics within soils, whereas polyethylene terephthalate (PET), polypropylene (PP), and PA prevailed within water. Microplastic particle sizes ranged from 39 to 2498 µm in soils, mainly from 29 to 3394 µm in water. The upstream section displayed higher abundances of microplastic compared to the downstream, revealing the soil particles having an intercepting effect on microplastics. The distribution and migration of microplastics in soil and groundwater are affected by many factors, including natural and anthropogenic factors, such as soil depth, soil properties, pore structure, hydrodynamics, hydraulic connections between groundwater and surface water, the extensive utilization and disposal of plastics, irrational exploitation of groundwater, and morphology and types of microplastics. These research findings contribute to a better understanding of the pathways, migration capacity, and influencing factors associated with microplastic entry into groundwater, thereby providing valuable technical support for the development of strategies aimed at controlling microplastic pollution.
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Monitoreo del Ambiente , Agua Subterránea , Microplásticos , Contaminantes del Suelo , Suelo , Contaminantes Químicos del Agua , Agua Subterránea/química , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Contaminantes del Suelo/análisis , Suelo/química , Ríos/química , ChinaRESUMEN
BACKGROUND: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood. METHOD: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways. RESULTS: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis. CONCLUSION: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies.
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Análisis de la Aleatorización Mendeliana , Urolitiasis , Humanos , Urolitiasis/sangre , Factores de RiesgoRESUMEN
It is said that all models are wrong, but some are useful. In vitro human cell-based models are a prime example of this maxim. We asked researchers: when is your model system useful? How can it be made more useful? What are its limitations?
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Modelos Biológicos , Humanos , Técnicas de Cultivo de Célula/métodosRESUMEN
It turns out that the more than trillion microorganisms living in the host's digestive tract are crucial for maintaining nutrient intake, environmental suitability, and physiological mechanism. Xinjiang fine-wool sheep is an exclusive breed for wool in China, which has excellent stress tolerance. In this study, we collected feces and blood samples of 20 Xinjiang fine-wool sheep under the same genetic characteristics, the Fine-Wool Sheep (FWS) group and the Control Fine-Wool Sheep (CFWS) group were set up according to the differs in phenotypic characteristics of their wool. By 16S rRNA amplicon sequence, ITS1 region amplicons and Targeted Metabolomics, we analyzed the microbial community structure of fecal microorganisms and Short Chain Fatty Acids (SCFAs) in serum of the Xinjiang fine-wool sheep. Fecal microbial sequencing showed that the bacterial composition and structure were similar between the two groups, whereas there were significant differences in the composition and structure of the fungal community. It was also found that the abundant of Neocallimastigomycota in the intestinal fungal community of FWS was higher. In addition, the results of the serum SCFAs content analysis showed that butyric acid was significantly differences than those two groups. Correlation analysis between SCFAs and bacteria found that butyric acid metabolism had positively correlated (P < 0.05) with Ruminococcus and UCG-005. Overall, our data provide more supplement about the gut microbes community composition and structure of the Xinjiang fine-wool sheep. These results might be useful for improving gut health of sheep and taking nutritional control measure to improve production traits of animals in future.
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Bacterias , Ácidos Grasos Volátiles , Heces , Microbioma Gastrointestinal , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Ribosómico 16S , Animales , Ovinos/microbiología , Heces/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , China , ARN Ribosómico 16S/genética , Ácidos Grasos Volátiles/metabolismo , Hongos/genética , Hongos/clasificación , Hongos/metabolismo , Lana/microbiología , FilogeniaRESUMEN
Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment.
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Lesión Renal Aguda , Ratones Endogámicos C57BL , Ratones Noqueados , Necroptosis , Receptores de Bombesina , Animales , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Humanos , Necroptosis/efectos de los fármacos , Ratones , Masculino , Línea Celular , Receptores de Bombesina/metabolismo , Receptores de Bombesina/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
Aqueous zinc metal batteries are regarded as a promising energy storage solution for a green and sustainable society in the future. However, the practical application of metallic zinc anode is plagued by the thermodynamic instability issue of water molecules in conventional electrolytes, which leads to severe dendrite growth and side reactions. In this work, an ultra-thin and high areal capacity metallic zinc anode is achieved by utilizing crystalline water with a stable stoichiometric ratio. Unlike conventional electrolytes, the designed electrolyte can effectively suppress the reactivity of water molecules and diminish the detrimental corrosion on the metallic zinc anode, while preserving the inherent advantages of water molecules, including great kinetic performance in electrolytes and H+ capacity contribution in cathodes. Based on the comprehensive performance of the designed electrolyte, the 10 µm Zn||10 µm Zn symmetric cell stably ran for 1000 h at the current density of 1 mA cm-2, and the areal capacity of 1 mAh cm-2, whose depth-of-discharge is over 17.1%. The electrochemical performance of the 10 µm Zn||9.3 mg cm-2 polyaniline (PANI) full-cell demonstrates the feasibility of the designed electrolyte. This work provides a crucial understanding of balancing activity of water molecules in aqueous zinc metal batteries.
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Electrochromic (EC) devices represent an emerging energy-saving technology, exhibiting the capability to dynamically modulate light and heat transmittance. Despite their promising potential, the commercialization of EC devices faces substantial impediments such as high cost, intricate fabrication process, and low optical contrast inherent in conventional EC materials relying on the ion insertion/extraction mechanism. In this study, we introduce an innovative "electrode-free" electrochromic (EC) device, termed the EECD, which lacks an EC-layer on the electrodes during device assembling and in the bleached state. This device features a simplified fabrication process and delivers superior optical modulation. It achieves a high optical contrast ranging from 68-85% across the visible spectrum and boasts a rapid response time, reaching 90% coloring in just 17 seconds. In addition, EECD exhibits stable cycling for over 10,000 cycles without noticeable degradation and maintains functionality across a broad temperature range (0 °C to 50 °C). Furthermore, the fabricated large-area devices (40 cm × 40 cm) demonstrate excellent tinting uniformity, suggesting excellent scalability of this approach. Our study establishes a paradigmatic breakthrough for EC smart windows.
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BACKGROUND AND INTENTION: Erectile dysfunction (ED) is an underappreciated clinical condition in men. This study aims to compare the dynamic changes in the distribution of ED among male kidney transplant recipients (mKTRs) in four epochs: end-stage renal disease period (ESRDp), early post-transplant period (EPTP), pre-COVID-19, and post-COVID-19. METHODS: General information was gathered through interviews, follow-ups, and medical records. The International Index of Erectile Function Questionnaire-5 was used to assess erectile function. The Mann-Whitney U test and chi-square test were used to analyze differences in ED strength. Univariate and logistic regression analyses were conducted to identify risk factors for ED. RESULTS: The database contains 230 mKTRs. In the ESRDp, 17.0% had normal erectile function, 53.5% had mild ED, 18.3% had moderate ED, and 11.3% had severe ED. In the EPTP, the distribution was 38.2% normal, 42.6% mild, 10.8% moderate, and 8.2% severe. In the pre-COVID-19 period, it was 34.3%, 47.3%, 10.4%, and 7.8%, and in the post-COVID-19 period, it was 23.0%, 45.6%, 21.3%, and 10.0%. Overall, erectile function improved after kidney transplant (KT). However, post-COVID-19, the proportion of erectile function significantly decreased compared to EPTP and pre-COVID-19 periods. Risk factors for post-pandemic ED included degree, Generalized Anxiexy Disorder-7, kidney donor type, postoperative time, hypertension and hemoglobin concentration. CONCLUSION: KT improves erectile function in mKTRs within 5 years, but post-SARS-CoV-2 viral infection, ED worsens due to altered risk factors. These findings inform future research for comprehensive ED prevention and management strategies in this population.
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COVID-19 , Disfunción Eréctil , Trasplante de Riñón , Receptores de Trasplantes , Humanos , Masculino , Trasplante de Riñón/efectos adversos , Disfunción Eréctil/etiología , Disfunción Eréctil/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , Persona de Mediana Edad , Adulto , Factores de Riesgo , Receptores de Trasplantes/estadística & datos numéricos , Fallo Renal Crónico/cirugía , SARS-CoV-2 , Factores de Tiempo , Encuestas y Cuestionarios , AncianoRESUMEN
Proteomics is a powerful method to comprehensively understand cellular posttranslational modifications (PTMs). Due to low abundance, tryptic peptides with PTMs are usually enriched for enhanced coverage by LC-MS/MS. Affinity chromatography for phosphoproteomes by metal-oxide and pan-specific antibodies for lysine acetylome allow identification of tens of thousands of modification sites. Lysine methylation is a significant PTM, however, only hundreds of methylation sites were identified from available approaches. Here we report an aryl diazonium-based chemoselective strategy that enables enrichment of monomethyllysine (Kme1) peptides via covalent bond with extraordinary sensitivity. We identified more than ten thousand Kme1 peptides from diverse cell lines and mouse tissues, that implied wide lysine methylation impact on cellular processes. In addition, we found a significant amount of methyl marks that were not S-adenosyl methionine (SAM)-dependent by isotope labeling experiments. And therefore, this method paves a way to broad application in lysine methylation research and new biology discovery.
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Optical-resolution photoacoustic microscopy (OR-PAM) has been increasingly utilized for in vivo imaging of biological tissues, offering structural, functional, and molecular information. In OR-PAM, it is often necessary to make a trade-off between imaging depth, lateral resolution, field of view, and imaging speed. To improve the lateral resolution without sacrificing other performance metrics, we developed a virtual-point-based deconvolution algorithm for OR-PAM (VP-PAM). VP-PAM has achieved a resolution improvement ranging from 43% to 62.5% on a single-line target. In addition, it has outperformed Richardson-Lucy deconvolution with 15 iterations in both structural similarity index and peak signal-to-noise ratio on an OR-PAM image of mouse brain vasculature. When applied to an in vivo glass frog image obtained by a deep-penetrating OR-PAM system with compromised lateral resolution, VP-PAM yielded enhanced resolution and contrast with better-resolved microvessels.
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Procesamiento de Imagen Asistido por Computador , Microscopía , Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Animales , Microscopía/métodos , Ratones , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Fenómenos Ópticos , Algoritmos , Relación Señal-Ruido , Microvasos/diagnóstico por imagenRESUMEN
Immunosuppression is a major hallmark of tumor progression in non-small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro-tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di-methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di-methylation of CD147 at Lys148 (CD147-K148me2) is identified as a common post-translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147-K148me2. Further analysis demonstrates that CD147-K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38-ZBTB32 signaling, leading to increased NSCLC cell-derived CCL5 secretion. Subsequently, CD147-K148me2-mediated CCL5 upregulation facilitates M2-like tumor-associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis-dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147-K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147-K148me2-driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM-targeted NSCLC therapy.
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Basigina , Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL5 , Neoplasias Pulmonares , Receptores CCR5 , Microambiente Tumoral , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Basigina/metabolismo , Basigina/genética , Ratones , Animales , Receptores CCR5/metabolismo , Receptores CCR5/genética , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Microambiente Tumoral/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Línea Celular Tumoral , Terapia de Inmunosupresión , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
BACKGROUND AND PURPOSE: The adenosine A2A receptor (A2AR) is involved in various physiological and pathological processes in the eye; however, the role of the A2AR signalling in corneal epithelial wound healing is not known. Here, the expression, therapeutic effects and signalling mechanism of A2AR in corneal epithelial wound healing were investigated using the A2AR agonist CGS21680. EXPERIMENTAL APPROACH: A2AR localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo-YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored. KEY RESULTS: A2AR expression was up-regulated after corneal epithelial injury. Topical administration of CGS21680 dose-dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A2AR activation promoted early up-regulation and later down-regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680-mediated wound healing effect in vivo and in vitro. CONCLUSION AND IMPLICATIONS: A2AR activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A2ARs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.
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Adenosina , Epitelio Corneal , Fenetilaminas , Receptor de Adenosina A2A , Transducción de Señal , Cicatrización de Heridas , Proteínas Señalizadoras YAP , Cicatrización de Heridas/efectos de los fármacos , Animales , Fenetilaminas/farmacología , Transducción de Señal/efectos de los fármacos , Adenosina/análogos & derivados , Adenosina/farmacología , Receptor de Adenosina A2A/metabolismo , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/metabolismo , Humanos , Ratones , Agonistas del Receptor de Adenosina A2/farmacología , Movimiento Celular/efectos de los fármacos , Masculino , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ratones Endogámicos C57BL , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Lesiones de la Cornea/tratamiento farmacológico , Lesiones de la Cornea/metabolismo , Lesiones de la Cornea/patologíaRESUMEN
Eutectogels based on natural polymers have attracted significant attention as an alternative to easily dehydrated hydrogels and expensive ionogels in the development of flexible strain sensors. The feasibility of employing eutectogels derived from pure natural polymers could be greatly enhanced if their mechanical properties satisfy the requirements of applications. Herein, alginate eutectogels (AEs) with high mechanical properties (tensile strain 217 % and strength 2.26 MPa at fracture), and excellent transparency (over 90 %) are acquired via CaCl2 inducing ionic crosslinking and subsequent deep eutectic solvents (DESs, composed of glycerol and choline chloride) initiating physical crosslinking with a universal solvent- replacement strategy. Among them, sodium alginate, a natural polysaccharide polymer, is selected as representative supporting scaffolds and forms water-insoluble alginate hydrogels (AHs) in CaCl2 coagulation bath. The exchange of DESs with water of AHs not only restrengthens the polymer network by physical crosslinking, but also endows the obtained AEs with long-term solvent retention and high temperature resistance. In addition, the AEs not only have high reliability but also exhibit better linear sensitivity in a wide strain range (0-200 %). In particular, the AEs display multiple sensitivity to stretching, bending, and human motions, demonstrating feasibility as sensitive strain sensors.
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Alginatos , Hidrogeles , Solventes , Alginatos/química , Hidrogeles/química , Solventes/química , Glicerol/química , Cloruro de Calcio/química , Humanos , Resistencia a la Tracción , Colina/química , TemperaturaRESUMEN
INTRODUCTION: The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. METHODS: We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). RESULTS: AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR] = 2.37, P < 0.01) and major depressive disorder (MDD; HR = 1.63, P < 0.001). MR confirmed a causal link between BD and AD (ORIVW = 1.098), as well as obsessive-compulsive disorder (OCD) and AD (ORIVW = 1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. DISCUSSION: Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. HIGHLIGHTS: This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR] = 2.37, P < 0.01), followed by those with major depressive disorder (MDD; HR = 1.63, P < 0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR = 2.36, P = 0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (ORIVW = 1.098, P < 0.05), as well as AD family history (proxy-AD, ORIVW = 1.098, P < 0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (ORIVW = 1.050, P < 0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.
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Enfermedad de Alzheimer , Bancos de Muestras Biológicas , Disfunción Cognitiva , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Reino Unido/epidemiología , Femenino , Masculino , Disfunción Cognitiva/genética , Disfunción Cognitiva/epidemiología , Factores de Riesgo , Persona de Mediana Edad , Anciano , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Trastorno Bipolar/genética , Trastorno Bipolar/epidemiología , Esquizofrenia/genética , Esquizofrenia/epidemiología , Biobanco del Reino UnidoRESUMEN
To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.
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Oro , Inmunoterapia , Nanopartículas del Metal , Platino (Metal) , Inmunoterapia/métodos , Ratones , Animales , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Oro/química , Fototerapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Modelos Animales de Enfermedad , Anisotropía , Catálisis , Humanos , Línea Celular TumoralRESUMEN
Germectomy is a common surgery in pediatric dentistry to prevent the potential dangers caused by impacted mandibular wisdom teeth. Segmentation of mandibular wisdom teeth is a crucial step in surgery planning. However, manually segmenting teeth and bones from 3D volumes is time-consuming and may cause delays in treatment. Deep learning based medical image segmentation methods have demonstrated the potential to reduce the burden of manual annotations, but they still require a lot of well-annotated data for training. In this paper, we initially curated a Cone Beam Computed Tomography (CBCT) dataset, NKUT, for the segmentation of pediatric mandibular wisdom teeth. This marks the first publicly available dataset in this domain. Second, we propose a semantic separation scale-specific feature fusion network named WTNet, which introduces two branches to address the teeth and bones segmentation tasks. In WTNet, We design a Input Enhancement (IE) block and a Teeth-Bones Feature Separation (TBFS) block to solve the feature confusions and semantic-blur problems in our task. Experimental results suggest that WTNet performs better on NKUT compared to previous state-of-the-art segmentation methods (such as TransUnet), with a maximum DSC lead of nearly 16%.
Asunto(s)
Tomografía Computarizada de Haz Cónico , Bases de Datos Factuales , Aprendizaje Profundo , Tercer Molar , Niño , Humanos , Algoritmos , Benchmarking/métodos , Tomografía Computarizada de Haz Cónico/métodos , Imagenología Tridimensional/métodos , Mandíbula/diagnóstico por imagen , Tercer Molar/diagnóstico por imagen , Conjuntos de Datos como AsuntoRESUMEN
The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery. Moreover, the incorporation of EGCG within ZIF-8 enables controlled degradation of the nanoparticles and the selective release of the encapsulated proteins in cancer cells. This selective release is triggered by the oxidation of EGCG in response to the high levels of reactive oxygen species (ROS) found within cancer cells that destabilize the EGCG/ZIF-8 nanoparticles. We have further demonstrated the ability of EGCG/ZIF-8 to deliver a wide range of proteins into cancer cells, including bacterial virulence protein, to rewire cell signaling and prohibit tumor cell growth in a mouse xenograft model. Our strategy and findings underscore the potential of designing the EGCG/ZIF-8 interface for specific and controlled protein delivery for targeted cancer therapy.