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1.
Int J Nanomedicine ; 19: 9227-9253, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267724

RESUMEN

Purpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy. Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved. Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the ß-catenin signaling pathway and other downstream genes without inducing acute toxicity. Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the ß-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.


Asunto(s)
Nanopartículas del Metal , MicroARNs , Neoplasias de la Boca , Plata , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , MicroARNs/administración & dosificación , MicroARNs/genética , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Humanos , Línea Celular Tumoral , Nanopartículas del Metal/química , Ratones , Plata/química , Plata/farmacología , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética
2.
ACS Nano ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238258

RESUMEN

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

3.
Front Cell Infect Microbiol ; 14: 1433359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185087

RESUMEN

Introduction: Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. Domestic animals, dogs, foxes, and small mammals constitute the circular chain of AE. To evaluate the infection, distribution, and genetic polymorphism of AE in the Ili Prefecture (Nilka, Xinyuan and Zhaosu), we conducted this survey. Methods: In June and July 2018, 267 small mammals were captured using water-infusion and mousetrap methods. Combined pathogenic and molecular biological methods were used to observe the histopathology of Echinococcus carried by rodents, amplify the mitochondrial nad1 gene of the pathogen, and investigate the genotype and haplotype diversity of Echinococcus in rodents in Ili Prefecture. Results: Morphological identification revealed that these captured small mammals belonged to three species, with Microtus gregalis being the dominant species (183/267). Pathological and molecular biological results confirmed that E. multilocularis was the pathogen of echinococcosis in small mammals, with an infection rate of 15.73% (42/267). Among the three areas sampled, the highest infection rate of rodents was 25.45% (14/55) in Nilka County. However, there was no significant difference in the infection rates between regions (χ2 = 5.119, p > 0.05). Of the three captured rodent species, M. gregalis had the highest infection rate of 17.49% (32/183), but there was no significant difference in infection rates between the rodent species (χ2 = 1.364, p > 0.05). Phylogenetic analyses showed that the nad1 gene sequences obtained in this study clustered in the same clade as isolates from China. These isolates contained 21 haplotypes (Hap_1-21); Hap_2 was the most common haplotype (9/42). Furthermore, haplotype diversity (0.925 ± 0.027) and nucleotide diversity (0.01139 ± 0.00119) were higher in the Ili Prefecture than in other regions, indicating that population differentiation was high. Tajima's D and Fu's Fs tests were negative (p > 0.10), indicating that the population had expanded. The low fixation index (Fst) ranged from 0.00000 to 0.16945, indicating that the degree of genetic differentiation was different among different populations. Discussion: In summary, Ili Prefecture is a high incidence area of AE, and Microtus spp. may play an important role in the transmission of AE in this area. The results of this study provide basic data for further study of the molecular epidemiology, genetic differences, and control of E. multilocularis in the Ili Prefecture, Xinjiang.


Asunto(s)
Equinococosis , Echinococcus multilocularis , Haplotipos , Polimorfismo Genético , Roedores , Animales , China/epidemiología , Equinococosis/epidemiología , Equinococosis/parasitología , Equinococosis/veterinaria , Roedores/parasitología , Echinococcus multilocularis/genética , Echinococcus multilocularis/aislamiento & purificación , Echinococcus multilocularis/clasificación , Genotipo , Filogenia , Echinococcus/genética , Echinococcus/clasificación , Echinococcus/aislamiento & purificación
4.
ChemSusChem ; : e202401458, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168828

RESUMEN

Complete discharge of spent lithium-ion batteries (LIBs) is a crucial step in LIB recycling, with the physical discharge method being particularly noted for its high discharge efficiency and environmental friendliness. However, previous studies and standards have focused on the performances of the discharge methods, neglecting the battery materials changes caused by discharge. Here we demonstrate that although prolonged discharge of spent batteries keeps the voltage around 0 V, an obvious current flow can be still observed, resulting from the dissolution and subsequent deposition of the copper foil. The deposited copper, primarily in the forms of Cu, Cu2O, and CuO, shows a gradient distribution on the surface of the anode and cathode active materials. This copper deposition significantly compromises the electrochemical performance of the discharged battery, with evident deterioration observed in the first charge-discharge capacity, cycling performance, and coulombic efficiency when compared to the original battery. This study provides guidance for the discharge methods and offers new insights into the materials failure mechanisms during discharge of spent batteries.

5.
ACS Nano ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020456

RESUMEN

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

6.
Langmuir ; 40(32): 16959-16971, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39078371

RESUMEN

A fundamental understanding of the fluid flow mechanism during CH4 hydrate dissociation in nanoscale clayey sediments from the molecular perspective can provide invaluable information for macroscale natural gas hydrate (NGH) exploration. In this work, the fluid flow behaviors of the decomposed gas from CH4 hydrate within clayey nanopores under different temperature conditions are revealed by molecular dynamics (MD) simulation. The simulation results indicate that the key influencing factors of gas-water flow in nanoscale clayey sediments include the diffusion and the random migration of gas molecules. The influencing mechanisms of fluid flow in nanopores are closely related with the temperature conditions. Under a low temperature condition, the gas diffusion process is impeded by the secondary hydrate formation, leading to the decline in gas transport velocity within nanopores. However, it is still noteworthy that the gas-water fluid flow channels are not completely blocked by the occurrence of secondary hydrate. Under a high temperature condition, the significant phenomenon of water migration during gas flow is observed, which can be ascribed to the gas-liquid entrainment effect in nanopores of the clayey sediment. These results may provide valuable implications and fundamental evidence for improving gas production efficiency in future field tests of NGH exploitation in marine sediments.

7.
Rev Cardiovasc Med ; 25(2): 54, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39077356

RESUMEN

Background: Acute kidney injury (AKI) frequently occurs after aortic surgery and has a significant impact on patient outcomes. Early detection or prediction of AKI is crucial for timely interventions. This study aims to develop and validate a novel model for predicting AKI following aortic surgery. Methods: We enrolled 156 patients who underwent on-pump aortic surgery in our hospital from February 2023 to April 2023. Postoperative levels of eight cytokines related to macrophage polarization analyzed using a multiplex cytokine assay. All-subset regression was used to select the optimal cytokines to predict AKI. A logistic regression model incorporating the selected cytokines was used for internal validation in combination with a bootstrapping technique. The model's ability to discriminate between cases of AKI and non-AKI was assessed using receiver operating characteristic (ROC) curve analysis. Results: Of the 156 patients, 109 (69.87%) developed postoperative AKI. Interferon-gamma (IFN- γ ) and interleukin-4 (IL-4) were identified as candidate AKI predictors. The cytokine-based model including IFN- γ and IL-4 demonstrated excellent discrimination (C-statistic: 0.90) and good calibration (Brier score: 0.11). A clinical nomogram was generated, and decision curve analysis revealed that the cytokine-based model outperformed the clinical factor-based model in terms of net benefit. Moreover, both IFN- γ and IL-4 emerged as independent risk factors for AKI. Patients in the second and third tertiles of IFN- γ and IL-4 concentrations had a significantly higher risk of severe AKI, a higher likelihood of requiring renal replacement therapy, or experiencing in-hospital death. These patients also had extended durations of mechanical ventilation and intensive care unit stays, compared with those in the first tertile (all p for group trend < 0.001). Conclusions: We successfully established a novel and powerful predictive model for AKI, and demonstrating the significance of IFN- γ and IL-4 as valuable clinical markers. These cytokines not only predict the risk of AKI following aortic surgery but are also linked to adverse in-hospital outcomes. This model offers a promising avenue for the early identification of high-risk patients, potentially improving clinical decision-making and patient care.

8.
J Oral Pathol Med ; 53(7): 434-443, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38825828

RESUMEN

BACKGROUND: Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions. METHODS: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS). RESULTS: The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site. CONCLUSION: Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.


Asunto(s)
Progresión de la Enfermedad , Neoplasias de la Boca , Ploidias , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Algoritmos , Citodiagnóstico/métodos , Detección Precoz del Cáncer , Neoplasias de la Boca/patología , Neoplasias de la Boca/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/genética , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad
9.
ChemSusChem ; 17(14): e202400466, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38727153

RESUMEN

As a result of full-scale ongoing global efforts, the power conversion efficiency (PCE) of the organic-inorganic metal halide perovskite has skyrocketed. Unfortunately, the long-term operational stability for commercialization standards is still lagging owing to intrinsic defects such as ion migration-induced degradation, undercoordinated Pb2+, and shallow defects initiated by disordered crystal growth. Herein, we employed multifunctional, non-volatile tetra-methyl guanidine hydrochloride [TMGHCL] ionic liquid (IL) as an additive to elucidate defects' passivation effects on organic-inorganic metal halide perovskite. More specifically, the formation of hydrogen bonds between H+ in GA+ and I- and coordinate bonding between Cl- and undercoordinated Pb2+ could significantly passivate these defects. The hypothesis was confirmed by both experimental and DFT simulations displaying that the optimized ratio of IL integration restrains ion migration, improving grains' size, and significantly elongating the carrier lifetime. Remarkably, the modified cell achieved a peak efficiency of 22.00 % with negligible hysteresis, compared to the control device's PCE of 20.12 %. In addition, the TMGHCL-based device retains its 93.29 % efficiency after 16 days of continuous exposure to air with a relative humidity of 35±5% and temperature of 25±5 °C. This efficient approach of adding IL to perovskites absorber can produce high PCE and has strong commercialization potential.

10.
J Hazard Mater ; 474: 134724, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38805819

RESUMEN

The cardiotoxic effects of various pollutants have been a growing concern in environmental and material science. These effects encompass arrhythmias, myocardial injury, cardiac insufficiency, and pericardial inflammation. Compounds such as organic solvents and air pollutants disrupt the potassium, sodium, and calcium ion channels cardiac cell membranes, leading to the dysregulation of cardiac function. However, current cardiotoxicity models have disadvantages of incomplete data, ion channels, interpretability issues, and inability of toxic structure visualization. Herein, an interpretable deep-learning model known as CardioDPi was developed, which is capable of discriminating cardiotoxicity induced by the human Ether-à-go-go-related gene (hERG) channel, sodium channel (Na_v1.5), and calcium channel (Ca_v1.5) blockade. External validation yielded promising area under the ROC curve (AUC) values of 0.89, 0.89, and 0.94 for the hERG, Na_v1.5, and Ca_v1.5 channels, respectively. The CardioDPi can be freely accessed on the web server CardioDPipredictor (http://cardiodpi.sapredictor.cn/). Furthermore, the structural characteristics of cardiotoxic compounds were analyzed and structural alerts (SAs) can be extracted using the user-friendly CardioDPi-SAdetector web service (http://cardiosa.sapredictor.cn/). CardioDPi is a valuable tool for identifying cardiotoxic chemicals that are environmental and health risks. Moreover, the SA system provides essential insights for mode-of-action studies concerning cardiotoxic compounds.


Asunto(s)
Aprendizaje Profundo , Canal de Sodio Activado por Voltaje NAV1.5 , Humanos , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/genética , Cardiotoxicidad/etiología , Canal de Potasio ERG1/metabolismo , Canal de Potasio ERG1/antagonistas & inhibidores , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/química , Cardiotoxinas/toxicidad , Cardiotoxinas/química
11.
Small ; : e2401347, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716685

RESUMEN

A challenge facing the chlor-alkali process is the lack of electrocatalyst with high activity and selectivity for the efficient industrial production of chlorine. Herein the authors report a new electrocatalyst that can generate multi-interface structure by in situ growth of graphdiyne on the surface of cobalt oxides (GDY/Co3O4), which shows great potential in highly selective and efficient chlorine production. This result is due to the strong electron transfer and high density charge transport between GDY and Co3O4 and the interconversion of the mixed valence states of the Co atoms itself. These intrinsic characteristics efficiently enhance the conductivity of the catalyst, facilitate the reaction kinetics, and improve the overall catalytic selectivity and activity. Besides, the protective effect of the formed GDY layer is remarkable endowing the catalyst with excellent stability. The catalyst can selectively produce chlorine in low-concentration of NaCl aqueous solution at room temperature and pressure with the highest Faraday efficiency of 80.67% and an active chlorine yield rate of 184.40 mg h-1 cm-2, as well as superior long-term stability.

12.
Hortic Res ; 11(4): uhae041, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38638682

RESUMEN

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38652094

RESUMEN

The high photoelectric conversion efficiency and low cost of perovskite solar cells (PSCs) have further inspired people's determination to push this technology toward industrialization. The high-quality perovskite films and high-efficiency and stable PSCs are the crucial factors. Ionic liquids have been proven to be an effective strategy for regulating high-quality perovskite films and high-performance PSCs. However, the regulation mechanism between ionic liquids and perovskites still needs further clarification. In this study, a novel sulfonic acid-functionalized ionic liquid, 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BSO3HMImOTf), was used as an effective additive to regulate high-quality perovskite films and high-performance devices. Microscopic mechanism studies revealed strong interactions between BSO3HMImOTf and Pb2+ ions as well as halogens in the perovskite. The perovskite film is effectively passivated with the controlled crystal growth, suppressed ion migration, facilitating to the greatly improved photovoltaic performance, and superior long-term stability. This article reveals the regulatory mechanism of sulfonic acid type ionic liquids through testing characterization and mechanism analysis, providing a new approach for the preparation of high-quality perovskite devices.

14.
J Nutr Educ Behav ; 56(7): 466-477, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38647517

RESUMEN

OBJECTIVE: The primary objective of this study was to develop and validate a Social Cognitive Theory-based instrument to identify psychosocial factors that influence diet and physical activity among Chinese children aged 10-12 years. DESIGN: This is a cross-sectional study, with data collected from questionnaires. SETTING: Two elementary schools in Beijing, China. PARTICIPANTS: Fourth to sixth-grade students (N = 1,486) aged 10-12 years were recruited. VARIABLES MEASURED: Gender, height, weight, nation, and grade were collected. Energy-balanced eating behaviors and their related sociopsychological factors were surveyed. ANALYSIS: Confirmatory factor analysis, Pearson correlations, Cronbach α index, and mediation analysis were used. RESULTS: (1) Confirmatory factor analysis revealed a 6-factor solution (51 items) and all factor loadings > 0.32, indicating that the model fitness was acceptable. (2) All correlation coefficients are statistically significant. All of the Cronbach α indexes were > 0.65, indicating acceptable reliability. (3) The mediating effect of goal intention and outcome expectations between self-efficacy and habit strength was statistically significant (P < 0.01), verifying the theory structure. CONCLUSIONS AND IMPLICATIONS: This questionnaire exhibits good internal consistency, reliability, and structural validity. It can be effectively employed to investigate energy-balanced eating behaviors related to the Social Cognitive Theory in Chinese children.


Asunto(s)
Ejercicio Físico , Conducta Alimentaria , Humanos , Niño , Masculino , Femenino , Estudios Transversales , Encuestas y Cuestionarios , Ejercicio Físico/psicología , Reproducibilidad de los Resultados , Conducta Alimentaria/psicología , China , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Pueblos del Este de Asia
15.
Adv Sci (Weinh) ; 11(23): e2401301, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38544484

RESUMEN

The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device-related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV-triggered polymerization of double-network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg-Gly-Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.


Asunto(s)
Hidrogeles , Polielectrolitos , Animales , Hidrogeles/química , Polielectrolitos/química , Perros , Apéndice Atrial/cirugía , Rayos Ultravioleta , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología
16.
Innovation (Camb) ; 5(2): 100565, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38379791

RESUMEN

Partial endothelial-to-mesenchymal transition (EndMT) is an intermediate phenotype observed in endothelial cells (ECs) undergoing a transition toward a mesenchymal state to support neovascularization during (patho)physiological angiogenesis. Here, we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4 (GTF2H4) as a positive regulator of this process. In addition, we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3 (ERCC3) to co-regulate partial EndMT. Furthermore, by using phosphorylation proteomics and site-directed mutagenesis, we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3 (NCOA3) at serine 1330, which promoted the interaction between NCOA3 and p65, resulting in the transcriptional activation of NF-κB and the NF-κB/Snail signaling axis during partial EndMT. In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury. Collectively, our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

17.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38339201

RESUMEN

Previous studies have shown that nuclear binding protein 2 (NUCB2) is expressed in the human placenta and increases with an increase in the syncytialization of trophoblast cells. This study aimed to investigate the role of NUCB2 in the differentiation and fusion of trophectoderm cells. In this study, the expression levels of NUCB2 and E-cadherin in the placentas of rats at different gestation stages were investigated. The results showed that there was an opposite trend between the expression of placental NUCB2 and E-cadherin in rat placentas in different trimesters. When primary human trophoblast (PHT) and BeWo cells were treated with high concentrations of Nesfatin-1, the trophoblast cell syncytialization was significantly inhibited. The effects of NUCB2 knockdown in BeWo cells and Forskolin-induced syncytialization were investigated. These cells showed a significantly decreased cell fusion rate. The mechanism underlying NUCB2-regulated trophoblast cell syncytialization was explored using RNA-Seq and the results indicated that the epidermal growth factor receptor (EGFR)-phospholipase C gamma 1 (PLCG1)-calmodulin-dependent protein kinase IV (CAMK4) pathway might be involved. The results suggested that the placental expression of NUCB2 plays an important role in the fusion of trophoblasts during differentiation via the EGFR-PLCG1-CAMK4 pathway.


Asunto(s)
Nucleobindinas , Placenta , Placentación , Trofoblastos , Animales , Femenino , Embarazo , Ratas , Cadherinas/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteínas Portadoras/metabolismo , Fusión Celular , Receptores ErbB/metabolismo , Proteínas Nucleares/metabolismo , Fosfolipasa C gamma/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Nucleobindinas/metabolismo
18.
J Am Chem Soc ; 146(8): 5669-5677, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38350029

RESUMEN

Advanced atomic-level heterointerface engineering provides a promising method for the preparation of next-generation catalysts. Traditional carbon-based heterointerface catalytic performance rely heavily on the undetermined defects in complex and demanding preparation processes, rendering it impossible to control the catalytic performance. Here, we present a general method for the controlled growth of metal atom arrays on graphdiyne (GDY/IrCuOx), and we are surprised to find strong heterointerface strains during the growth. We successfully controlled the thickness of GDY to regulate the heterointerface metal atoms and achieved compressive strain at the interface. Experimental and density functional theory calculation results show that the unique incomplete charge transfer between GDY and metal atoms leads to the formation of strong interactions and significant heterointerface compressive strain between GDY and IrCuOx, which results in high oxidation performances with 1000 mA cm-2 at a low overpotential of 283 mV and long-term stability at large current densities in alkaline simulated seawater. We anticipate that this finding will contribute to construction of high-performance heterogeneous interface structures, leading to the development of new generation of GDY-based heterojunction catalysts in the field of catalysis for future promising performance.

19.
Plant Physiol ; 195(1): 652-670, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38412470

RESUMEN

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.


Asunto(s)
Alelos , Genoma de Planta , Populus , Populus/genética , Genoma de Planta/genética , Regulación de la Expresión Génica de las Plantas , Haplotipos/genética , Hibridación Genética , Aprendizaje Automático
20.
Adv Healthc Mater ; 13(13): e2303674, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38315148

RESUMEN

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.


Asunto(s)
Alginatos , Endometrio , Exosomas , Hidrogeles , Regeneración , Células del Estroma , Femenino , Alginatos/química , Exosomas/metabolismo , Exosomas/química , Animales , Hidrogeles/química , Hidrogeles/farmacología , Endometrio/citología , Endometrio/metabolismo , Ratones , Regeneración/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/citología , Decidua/citología , Decidua/metabolismo , Fertilidad/fisiología , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Adherencias Tisulares/metabolismo
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