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1.
Mycoses ; 67(9): e13785, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39245647

RESUMEN

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.


Asunto(s)
Antifúngicos , Consenso , Farmacorresistencia Fúngica , Tiña , Humanos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , China , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/diagnóstico , Trichophyton/efectos de los fármacos , Trichophyton/aislamiento & purificación
2.
J Virol ; 98(9): e0078424, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39194214

RESUMEN

Porcine respiratory and reproductive syndrome (PRRS) is one of the most devastating infectious diseases of pigs, causing reproductive failures in sows and severe respiratory symptoms in piglets and growing pigs. MicroRNAs (miRNAs) are reported to play an essential role in virus-host interactions. In this study, we demonstrated that miR-451 enhanced type I interferon (IFN-I) production through targeting proteasome subunit ß8 (PSMB8), therefore restricting PRRS virus (PRRSV) replication. We showed that the expression of PSMB8 was upregulated by PRRSV infection, and knockdown of PSMB8 inhibited PRRSV replication by promoting IFN-I production. Moreover, we demonstrated that PSMB8 interacted with the regulatory domain of IRF3 to mediate K48-linked polyubiquitination and degradation of IRF3. Also, importantly, we showed that PSMB8, as a target gene of miR-451, negatively regulated IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to modulate innate immune responses. IMPORTANCE: Porcine respiratory and reproductive syndrome virus (PRRSV), as a huge threat to the swine industry, is a causative agent that urgently needs to be solved. The dissecting of PRRSV pathogenesis and understanding of the host-pathogen interaction will provide insights into developing effective anti-PRRSV strategies. In this study, we showed that miR-451 dramatically inhibited PRRSV replication by targeting proteasome subunit ß8 (PSMB8), a subunit of the immunoproteasome. Mutation of PSMB8 is often related to autoinflammatory diseases due to the elevated IFN production. We revealed that PSMB8 downregulated IFN production by promoting IRF3 degradation. In addition, we showed that PRRSV infection upregulated PSMB8 expression. Taken together, our findings reveal that miR-451 is a negative regulator of PRRSV replication, and PSMB8, a target gene of miR-451, negatively regulates IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to regulate innate immune responses.


Asunto(s)
Factor 3 Regulador del Interferón , MicroARNs , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Complejo de la Endopetidasa Proteasomal , Replicación Viral , Animales , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Porcinos , MicroARNs/genética , MicroARNs/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Humanos , Interferón Tipo I/metabolismo , Ubiquitinación , Inmunidad Innata , Línea Celular , Células HEK293 , Interacciones Huésped-Patógeno/genética , Proteolisis
3.
BMC Womens Health ; 24(1): 442, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39098907

RESUMEN

OBJECTIVE: Breast cancer has become the most prevalent malignant tumor in women, and the occurrence of distant metastasis signifies a poor prognosis. Utilizing predictive models to forecast distant metastasis in breast cancer presents a novel approach. This study aims to utilize readily available clinical data and advanced machine learning algorithms to establish an accurate clinical prediction model. The overall objective is to provide effective decision support for clinicians. METHODS: Data from 239 patients from two centers were analyzed, focusing on clinical blood biomarkers (tumor markers, liver and kidney function, lipid profile, cardiovascular markers). Spearman correlation and the least absolute shrinkage and selection operator regression were employed for feature dimension reduction. A predictive model was built using LightGBM and validated in training, testing, and external validation cohorts. Feature importance correlation analysis was conducted on the clinical model and the comprehensive model, followed by univariate and multivariate regression analysis of these features. RESULTS: Through internal and external validation, we constructed a LightGBM model to predict de novo bone metastasis in newly diagnosed breast cancer patients. The area under the receiver operating characteristic curve values of this model in the training, internal validation test, and external validation test1 cohorts were 0.945, 0.892, and 0.908, respectively. Our validation results indicate that the model exhibits high sensitivity, specificity, and accuracy, making it the most accurate model for predicting bone metastasis in breast cancer patients. Carcinoembryonic Antigen, creatine kinase, albumin-globulin ratio, Apolipoprotein B, and Cancer Antigen 153 (CA153) play crucial roles in the model's predictions. Lipoprotein a, CA153, gamma-glutamyl transferase, α-Hydroxybutyrate dehydrogenase, alkaline phosphatase, and creatine kinase are positively correlated with breast cancer bone metastasis, while white blood cell ratio and total cholesterol are negatively correlated. CONCLUSION: This study successfully utilized clinical blood biomarkers to construct an artificial intelligence model for predicting distant metastasis in breast cancer, demonstrating high accuracy. This suggests potential clinical utility in predicting and identifying distant metastasis in breast cancer. These findings underscore the potential prospect of developing economically efficient and readily accessible predictive tools in clinical oncology.


Asunto(s)
Inteligencia Artificial , Biomarcadores de Tumor , Neoplasias Óseas , Neoplasias de la Mama , Humanos , Neoplasias de la Mama/patología , Femenino , Neoplasias Óseas/secundario , Neoplasias Óseas/sangre , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Adulto , Anciano , Curva ROC , Aprendizaje Automático , Valor Predictivo de las Pruebas
4.
Huan Jing Ke Xue ; 45(8): 4627-4635, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168682

RESUMEN

Under the "dual-carbon" strategic goals, it is urgent to examine whether the energy consumption permit trading scheme (ECPTS), as an innovative system in China's market-oriented reform of the energy sector, can promote the synergistic enhancement of pollution reduction and carbon abatement. Based on provincial panel data of China from 2008 to 2019, this study adopted a difference-in-differences model to examine the impacts of the ECPTS on the synergistic enhancement of pollution reduction and carbon abatement. The results demonstrated that the ECPTS improved the level of pollution reduction and carbon abatement in pilot areas. Specifically, the ECPTS led to a reduction of 13.3% in CO2 emissions and 3.1% in PM2.5 concentration in the pilot areas and resulted in an overall improvement of pollution reduction and carbon abatement by 0.237 units. Mechanism analysis revealed that energy efficiency served as a pathway through which the ECPTS empowered the synergistic enhancement of pollution reduction and carbon abatement. Moreover, the strengthening of local government environmental protection goals enhanced the pollution reduction and carbon abatement effects of the ECPTS. Surprisingly, the effectiveness of the ECPTS was not undermined by the goal of economic growth. This study provides new empirical evidence for understanding the relationship between market-based environmental regulation and collaborative governance and provides strong support for China to achieve its "dual-carbon" strategic goals.

5.
Zool Res ; 45(5): 1048-1060, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39147719

RESUMEN

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.


Asunto(s)
Cadherinas , Adhesión Celular , Animales , Masculino , Porcinos , Adhesión Celular/fisiología , Ratones , Cadherinas/metabolismo , Cadherinas/genética , Ratones Noqueados , Espermatogonias/metabolismo , Espermatogonias/fisiología , Testículo/metabolismo , Testículo/fisiología , Células Madre Germinales Adultas/metabolismo , Células Madre Germinales Adultas/fisiología , Regulación de la Expresión Génica , Células Madre/fisiología , Células Madre/metabolismo
6.
Nat Commun ; 15(1): 7570, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217168

RESUMEN

The discovery of superconductivity with a critical temperature of about 80 K in La3Ni2O7 single crystals under pressure has received enormous attention. La3Ni2O7 is not superconducting under ambient pressure but exhibits a transition at T ∗ ≃ 115 K. Understanding the electronic correlations and charge dynamics is an important step towards the origin of superconductivity and other instabilities. Here, our optical study shows that La3Ni2O7 features strong electronic correlations which significantly reduce the electron's kinetic energy and place this system in the proximity of the Mott phase. The low-frequency optical conductivity reveals two Drude components arising from multiple bands at the Fermi level. The transition at T ∗ removes the Drude component exhibiting non-Fermi liquid behavior, whereas the one with Fermi-liquid behavior is barely affected. These observations in combination with theoretical results suggest that the Fermi surface dominated by the Ni- d 3 z 2 - r 2 orbital is removed due to the transition at T ∗. Our experimental results provide pivotal information for understanding the transition at T ∗ and superconductivity in La3Ni2O7.

7.
Front Oncol ; 14: 1409273, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947897

RESUMEN

Objective: This study aims to develop an artificial intelligence model utilizing clinical blood markers, ultrasound data, and breast biopsy pathological information to predict the distant metastasis in breast cancer patients. Methods: Data from two medical centers were utilized, Clinical blood markers, ultrasound data, and breast biopsy pathological information were separately extracted and selected. Feature dimensionality reduction was performed using Spearman correlation and LASSO regression. Predictive models were constructed using LR and LightGBM machine learning algorithms and validated on internal and external validation sets. Feature correlation analysis was conducted for both models. Results: The LR model achieved AUC values of 0.892, 0.816, and 0.817 for the training, internal validation, and external validation cohorts, respectively. The LightGBM model achieved AUC values of 0.971, 0.861, and 0.890 for the same cohorts, respectively. Clinical decision curve analysis showed a superior net benefit of the LightGBM model over the LR model in predicting distant metastasis in breast cancer. Key features identified included creatine kinase isoenzyme (CK-MB) and alpha-hydroxybutyrate dehydrogenase. Conclusion: This study developed an artificial intelligence model using clinical blood markers, ultrasound data, and pathological information to identify distant metastasis in breast cancer patients. The LightGBM model demonstrated superior predictive accuracy and clinical applicability, suggesting it as a promising tool for early diagnosis of distant metastasis in breast cancer.

8.
Sci Rep ; 14(1): 15561, 2024 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-38969798

RESUMEN

Breast cancer metastasis significantly impacts women's health globally. This study aimed to construct predictive models using clinical blood markers and ultrasound data to predict distant metastasis in breast cancer patients, ensuring clinical applicability, cost-effectiveness, relative non-invasiveness, and accessibility of these models. Analysis was conducted on data from 416 patients across two centers, focusing on clinical blood markers (tumor markers, liver and kidney function indicators, blood lipid markers, cardiovascular biomarkers) and maximum lesion diameter from ultrasound. Feature reduction was performed using Spearman correlation and LASSO regression. Two models were built using LightGBM: a clinical model (using clinical blood markers) and a combined model (incorporating clinical blood markers and ultrasound features), validated in training, internal test, and external validation (test1) cohorts. Feature importance analysis was conducted for both models, followed by univariate and multivariate regression analyses of these features. The AUC values of the clinical model in the training, internal test, and external validation (test1) cohorts were 0.950, 0.795, and 0.883, respectively. The combined model showed AUC values of 0.955, 0.835, and 0.918 in the training, internal test, and external validation (test1) cohorts, respectively. Clinical utility curve analysis indicated the combined model's superior net benefit in identifying breast cancer with distant metastasis across all cohorts. This suggests the combined model's superior discriminatory ability and strong generalization performance. Creatine kinase isoenzyme (CK-MB), CEA, CA153, albumin, creatine kinase, and maximum lesion diameter from ultrasound played significant roles in model prediction. CA153, CK-MB, lipoprotein (a), and maximum lesion diameter from ultrasound positively correlated with breast cancer distant metastasis, while indirect bilirubin and magnesium ions showed negative correlations. This study successfully utilized clinical blood markers and ultrasound data to develop AI models for predicting distant metastasis in breast cancer. The combined model, incorporating clinical blood markers and ultrasound features, exhibited higher accuracy, suggesting its potential clinical utility in predicting and identifying breast cancer distant metastasis. These findings highlight the potential prospects of developing cost-effective and accessible predictive tools in clinical oncology.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Metástasis de la Neoplasia , Humanos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Adulto , Ultrasonografía/métodos , Anciano
9.
J Am Chem Soc ; 146(30): 21110-21119, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39036901

RESUMEN

It is well-known that magnetic moments are very harmful to superconductivity. A typical example is the element Mn, whose compounds usually exhibit strong magnetism. Thus, it is very difficult to achieve superconductivity in materials containing Mn. Here, we report enhanced superconductivity with a superconducting transition temperature (Tc) up to a record-high value of about 26 K in a beta-phase Ti1-xMnx alloy containing the rich magnetic element Mn under high pressures. This is contrary to the intuition that magnetic moments always suppress superconductivity. Under high pressures, we also found that in the middle-pressure regime, the Pauli limit of the upper critical field is surpassed. The synchrotron X-ray diffraction data show an unchanged beta-phase with a continuous contraction of the cell volume, which is well-supported by the first-principles calculations. Although the theoretical results based on electron-phonon coupling can interpret the Tc value in a certain pressure region, the monotonic enhancement of superconductivity by pressure cannot seek support from the theory. Our results show a surprising enhancement of superconductivity in the Ti1-xMnx alloy with a considerable Mn content.

10.
J Phys Chem A ; 128(28): 5459-5472, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38973649

RESUMEN

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

11.
Bioconjug Chem ; 35(7): 934-943, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38935869

RESUMEN

Membrane tension is an important physical parameter of describing cellular homeostasis, and it is widely used in the study of cellular processes involving membrane deformation and reorganization, such as cell migration, cell spreading, and cell division. Despite the importance of membrane tension, direct measurement remains difficult. In this work, we developed a ratiometric fluorescent probe sensitive to membrane tension by adjusting the carbon chain structure based on polarity-sensitive fluorophores. The probe is sensitive to changes in membrane tension after cells were subjected to physical or chemical stimuli, such as osmotic shock, lipid peroxidation, and mechanical stress. When the polarity of the plasma membrane increases (the green/red ratio decreases) and the membrane tension increases, the relative magnitude of the membrane tension can be quantitatively calculated by fluorescence ratio imaging. Thus, the probe proved to be an efficient and sensitive membrane tension probe.


Asunto(s)
Membrana Celular , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Membrana Celular/metabolismo , Humanos , Imagen Óptica/métodos , Animales , Presión Osmótica , Estrés Mecánico
12.
Nat Commun ; 15(1): 5104, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877022

RESUMEN

The recent discovery of superconductivity in infinite-layer nickelate films has sparked significant interest and expanded the realm of superconductors, in which the infinite-layer structure and proper chemical doping are both of the essence. Nonetheless, the reasons for the absence of superconductivity in bulk infinite-layer nickelates remain puzzling. Herein, we investigate atomic defects and electronic structures in bulk infinite-layer Nd0.8Sr0.2NiO2 using scanning transmission electron microscopy. Our observations reveal the presence of three-dimensional (3D) block-like structural domains resulting from intersecting defect structures, disrupting the continuity within crystal grains, which could be a crucial factor in giving rise to the insulating character and inhibiting the emergence of superconductivity. Moreover, the infinite-layer structure, without complete topotactic reduction, retains interstitial oxygen atoms on the Nd atomic plane in bulk nickelates, possibly further aggravating the local distortions of NiO2 planes and hindering the superconductivity. These findings shed light on the existence of structural and atomic defects in bulk nickelates and provide valuable insights into the influence of proper topotactic reduction and structural orders on superconductivity.

13.
Cells ; 13(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38727297

RESUMEN

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Fusión Vertebral , Animales , Exosomas/metabolismo , Exosomas/trasplante , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Fusión Vertebral/métodos , Ratas , Osteogénesis/efectos de los fármacos , Fosfatos de Calcio/farmacología , Masculino , Humanos , Andamios del Tejido/química , Proteína Morfogenética Ósea 2/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos
14.
Angew Chem Int Ed Engl ; 63(31): e202405891, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-38769062

RESUMEN

Organic solvent nanofiltration (OSN) plays important roles in pharmaceutical ingredients purification and solvent recovery. However, the low organic solvent permeance under cross-flow operation of OSN membrane hampers their industrial applications. Herein, we report the construction of coffee-ring structured membrane featuring high OSN permeance. A water-insoluble crystal monomer that dissolved in EtOH/H2O mixed solvent was designed to react with trimesoyl chloride via interfacial polymerization. Owing to the diffusion of EtOH to n-hexane, coffee-ring nanostructure on the support membrane appeared, which served as the template for construction of coffee-ring structured membrane. The optimal nanostructured membrane demonstrated 2.6-fold enhancement in the effective surface area with reduced membrane thickness. Resultantly, the membrane afforded a 2.7-fold enhancement in organic solvent permeance, e.g., ~13 LMH/bar for MeOH, without sacrificing the rejection ability. Moreover, due to the rigid monomer structure, the fabricated membrane shows distinctive running stability in active pharmaceutical ingredients purification and the ability for concentration of medicines.

15.
Anal Chem ; 96(21): 8501-8509, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38717985

RESUMEN

Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.


Asunto(s)
Membrana Celular , Colesterol , Transferencia Resonante de Energía de Fluorescencia , SARS-CoV-2 , Esfingomielinas , Transferencia Resonante de Energía de Fluorescencia/métodos , Humanos , Membrana Celular/metabolismo , Membrana Celular/química , Esfingomielinas/análisis , Esfingomielinas/metabolismo , Colesterol/análisis , Colesterol/metabolismo , Microscopía Confocal/métodos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , COVID-19/virología , Enzima Convertidora de Angiotensina 2/metabolismo , Técnicas Biosensibles/métodos
16.
Front Neurol ; 15: 1400270, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38798706

RESUMEN

Background: Hemorrhagic transformation (HT) is a serious complication after endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS). We analyzed the plasma levels of MMP-9 before and after EVT and assessed the temporal changes of MMP-9 that may be associated with, and therefore predict, HT after EVT. Methods: We enrolled 30 AIS patients who received EVT, and 16 (53.3%) developed HT. The levels of MMP-9 in plasma collected from the arteries of AIS patients before and immediately after EVT were measured using ELISA. The percent change in MMP-9 after EVT (after/before) was calculated and compared between patients with and without HT. Results: The median age of the AIS patients was 70 years, and 13 patients (43.3%) were men. The median National Institutes of Health Stroke Scale (NIHSS) scores of patients with HT were 18 on admission and 18 after EVT. The median NIHSS scores of patients without HT were 17 on admission and 11 after EVT. Patients with HT demonstrated significantly greater percentage increases in arterial MMP-9 levels after EVT. Conclusion: Patients with AIS who developed HT had significantly increased arterial MMP-9 levels after EVT, suggesting that the upregulation of MMP-9 following EVT could serve as a predictive biomarker for HT.

17.
Heliyon ; 10(7): e28618, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38586389

RESUMEN

Background: The aim of this study was to investigate the effect of DNA methylation of Fork Head Box O3 (FOXO3a) on the process of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Methods: The expressions of FOXO3a, DNA methyltransferase 1 (DNMT1), METTL3, and EMT-related proteins (E-cadherin and N-cadherin) were measured. The influence of 5-Aza-dC and DNMT1 on the methylation level in the promoter region of FOXO3a was examined through the application of methylation-specific PCR (MSP). Chromatin immunoprecipitation (ChIP) was employed to detect binding between DNMT1 and the FOXO3a promoter. Methylated RNA immunoprecipitation (MeRIP) was utilized to evaluate the level of DNMT1 N6-methyladenosine (m6A) methylation. The assessment of cell viability and invasion abilities of A549 cells was performed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. NSCLC xenograft mouse models were established by subcutaneously injected treated A549 cells into nude mice. Results: The expression levels of DNMT1 and DNA methylation level FOXO3a were found to be significantly increased, whereas FOXO3a expression was considerably decreased in NSCLC cell lines and NSCLC tumor tissues. Both 5-Aza-dC treatment and DNMT1 knockdown resulted in the down-regulation of DNA methylation levels of FOXO3a while simultaneously up-regulating the expression of FOXO3a. A ChIP assay demonstrated that DNMT1 has the ability to bind to the promoter region of FOXO3a. Furthermore, the knockdown of DNMT1 promoted E-cadherin expression, but inhibited expression of N-cadherin, cell viability, and invasion ability. However, the knockdown of FOXO3a hindered the effect of DNMT1 knockdown on EMT, cell viability, and invasion ability of A549 cells. This was evidenced by decreased E-cadherin expression and increased N-cadherin expression, as well as increased cell viability and invasion ability. Increased expression of DNMT1 resulted from m6A methylation of DNMT1, which was mediated by METTL3. Overexpression of DNMT1 decreased of E-cadherin expression while increased N-cadherin expression, cell viability, and invasion ability in METTL3-shRNA treated A549 cells. In xenograft mouse models, DNMT1 knockdown significantly reduced tumor volumes and tumor weight. DNMT1 knockdown upregulated the expression of FOXO3a and E-cadherin, while downregulated N-cadherin expression in vivo. Conclusion: METTL3-mediated m6A methylation of DNMT1 up-regulates FOXO3a promoter methylation, thereby promoting the progression of NSCLC.

18.
Anal Chem ; 96(18): 7231-7239, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38656982

RESUMEN

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.


Asunto(s)
Técnicas Electroquímicas , Mediciones Luminiscentes , Nanotubos , Puntos Cuánticos , Puntos Cuánticos/química , Humanos , Técnicas Electroquímicas/métodos , Nanotubos/química , Mediciones Luminiscentes/métodos , Células HeLa , Membrana Celular/metabolismo , Membrana Celular/química , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Carbono/química
19.
Sci Rep ; 14(1): 9580, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671053

RESUMEN

Kagome superconductors AV3Sb5 (A = K, Rb, and Cs) have attracted enormous interest due to the coexistence of charge density wave (CDW) order, unconventional superconductivity (SC) and anomalous Hall effect (AHE). In this paper, we reported an intensive investigation on Cs(V1-xTax)3Sb5 single crystals with systematic Ta doping. Ta was confirmed to be doped into V-site in the Kagome layer from both single crystal X-ray diffraction structural refinement and scanning transmission electron microscopy observation. The highest Ta doping level was found to be about 16%, which is more than twice as much as 7% in Nb-doped CsV3Sb5. With the increase of Ta doping, CDW order was gradually suppressed and finally vanished when the doping level reached to more than 8%. Meanwhile, superconductivity was enhanced with a maximum critical temperature (Tc) of 5.3 K, which is the highest Tc in the bulk crystal of this Kagome system at ambient pressure so far. The µ0Hc2(T) behavior demonstrates that the system is still a two-band superconductor after Ta doping. Based on the electrical transport measurement, a phase diagram was set up to exhibit the evolution of CDW and SC in the Cs(V1-xTax)3Sb5 system. These findings pave a new way to search for new superconductors with higher Tc in the AV3Sb5 family and establish a new platform for tuning and controlling the multiple orders and superconducting states.

20.
Biomolecules ; 14(3)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38540757

RESUMEN

Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4, kidney cxcr3 and cxcr4, and spleen cxcr3, cxcr4, and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1, kidney cxcr1 and cxcr7, and liver cxcr2, cxcr3, and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.


Asunto(s)
Oncorhynchus mykiss , Animales , Humanos , Oncorhynchus mykiss/genética , Genoma , Transducción de Señal , Mamíferos/genética
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