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1.
BMC Cancer ; 24(1): 1226, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367321

RESUMEN

BACKGROUND: Colon cancer, a frequently encountered malignancy, exhibits a comparatively poor survival prognosis. Perineural invasion (PNI), highly correlated with tumor progression and metastasis, is a substantial effective predictor of stage II-III colon cancer. Nonetheless, the lack of effective and facile predictive methodologies for detecting PNI prior operation in colon cancer remains a persistent challenge. METHOD: Pre-operative computer tomography (CT) images and clinical data of patients diagnosed with stage II-III colon cancer between January 2015 and December 2023 were obtained from two sub-districts of Sun Yat-sen Memorial Hospital (SYSUMH). The LASSO/RF/PCA filters were used to screen radiomics features and LR/SVM models were utilized to construct radiomics model. A comprehensive model, shown as nomogram finally, combining with radiomics score and significant clinical features were developed and validated by area under the curve (AUC) and decision curve analysis (DCA). RESULT: The total cohort, comprising 426 individuals, was randomly divided into a development cohort and a validation cohort as a 7:3 ratio. Radiomics scores were extracted from LASSO-SVM models with AUC of 0.898/0.726 in the development and validation cohorts, respectively. Significant clinical features (CA199, CA125, T-stage, and N-stage) were used to establish combining model with radiomics scores. The combined model exhibited superior reliability compared to single radiomics model in AUC value (0.792 vs. 0.726, p = 0.003) in validation cohorts. The radiomics-clinical model demonstrated an AUC of 0.918/0.792, a sensitivity of 0.907/0.813 and a specificity of 0.804/0.716 in the development and validation cohorts, respectively. CONCLUSION: The study developed and validated a predictive nomogram model combining radiomics scores and clinical features, and showed good performance in predicting PNI pre-operation in stage II-III colon cancer patients.


Asunto(s)
Neoplasias del Colon , Invasividad Neoplásica , Estadificación de Neoplasias , Nomogramas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Adulto , Pronóstico , Estudios Retrospectivos , Nervios Periféricos/patología , Nervios Periféricos/diagnóstico por imagen , Radiómica
2.
Phytomedicine ; 135: 156047, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39321687

RESUMEN

BACKGROUND: Hepatic fibrosis is a pathological process in a variety of acute or chronic liver injuries. Catalpol (CAT), an iridoid glycoside found in Rehmannia glutinosa, has several pharmacological properties, including anti-inflammatory, antidiabetic and anti-fibrotic effects. Nevertheless, there is currently no report on whether CAT regulates the aerobic glycolysis of hepatic stellate cells (HSCs) to inhibit liver fibrosis. OBJECTIVE: This study aimed to investigate the protective effects of CAT on hepatic fibrosis and elucidate its underlying mechanisms. METHODS: To explore whether CAT improved liver fibrosis in vivo and in vitro, hepatic fibrosis was induced to mice by intraperitoneally injecting carbon tetrachloride (CCl4). Additionally, LX-2 cells were stimulated with transforming growth factor-ß (TGF-ß) to simulate fibrosis in vitro. Serum markers of liver injury were examined by using an automatic biochemical analyzer. Histopathological staining, Immunofluorescence (IF) staining, Western blot (WB) analysis, co-immunoprecipitation (Co-IP), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), etc. were employed to identify the targeting between CAT and EphA2 and detect the expression of aerobic glycolysis related proteins, fiber markers and signaling pathways that are responsible for CAT's anti-fibrotic effects of CAT. RESULTS: Results showed that CAT significantly inhibited hepatic injury, fibrogenesis and inflammation in mice treated with CCl4. This was demonstrated by the enhancement of fibrosis markers, liver function indices, and histopathology. In addition, CAT significantly inhibited the activation of HSCs in TGF-ß-induced LX-2 cells, as indicated by decreased proliferation, migration, and expression of collagen I and a-SMA. The study results also suggested that CAT may exert anti-fibrotic effects by inhibiting glycolysis in activated HSCs and in CCl4-treated mice. Mechanistically, CAT directly targets Ephrin type-A receptor 2 (EphA2) to reduce binding with focal adhesion kinases (FAK) and significantly inhibits the FAK/Src pathway. In addition, the pharmacological inhibition of EphA2 cannot further increase the therapeutic effects of CAT on liver fibrosis in vivo and in vitro. CONCLUSION: The study findings generally demonstrated that CAT presented a novel therapeutic method to treat hepatic fibrosis; this method which inhibits the aerobic glycolysis of activated HSCs through the EphA2/FAK/Src signaling pathway.

3.
Europace ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331050

RESUMEN

BACKGROUND: Advanced ablation strategies are needed to treat ventricular tachycardia (VT) and premature ventricular contractions (PVC) refractory to standard unipolar radiofrequency ablation (Uni-RFA). Bipolar radiofrequency catheter ablation (Bi-RFA) has emerged as a treatment option for refractory VT, PVC. Multicenter registry data on the use of Bi-RFA in the setting of refractory VT and PVC are lacking. PURPOSE: The aim of this Bi-RFA registry is to determine its real-world safety, feasibility, and efficacy in patients with refractory VT/PVC. METHODS: Consecutive patients undergoing Bi-RFA at sixteen European centers for recurring VT/PVC after at least one standard Uni-RFA were included. Second ablation catheter was used instead of a dispersive patch and was positioned at the opposite site of the ablation target. RESULTS: Between March 2021 and August 2024, ninety-one patients underwent 94 Bi-RFA procedures (74 males, age 62±13, prior Uni-RFA range 1-8). Indications were recurrence of PVC (n=56), VT (n=20), electrical storm (n=13), or PVC-triggered ventricular fibrillation (n=2). Procedural time was 160±73min, Bi-RFA time 426±286s, mean Uni-RFA time 819±697s. Elimination of clinical VT/PVC was achieved in 67 (74%) patients, suppression of VT/PVC in a further 10 (11%) patients. In the remaining 14 patients (15%) no effect on VT/PVC was observed. Three major complications occurred: coronary artery occlusion, AV block and arteriovenous fistula. Follow-up lasted 7±8 months. Nineteen (61%) remained VT-free. ≥80% PVC burden reduction was achieved in 45 (78%). CONCLUSIONS: This real-world registry data indicates that Bi-RFA appears safe, is feasible, and effective in the majority of patients with VT/PVC.

4.
J Am Coll Cardiol ; 84(13): 1178-1189, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39217551

RESUMEN

BACKGROUND: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.


Asunto(s)
Sistema de Registros , Cardiomiopatía de Takotsubo , Humanos , Cardiomiopatía de Takotsubo/epidemiología , Cardiomiopatía de Takotsubo/mortalidad , Cardiomiopatía de Takotsubo/diagnóstico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Factores de Tiempo
5.
Heart Rhythm ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284398

RESUMEN

BACKGROUND: Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared with men. However, the underlying mechanism remains unclear. OBJECTIVE: The purpost of this study was to investigate the mechanism through which menopause promotes atrial fibrosis. METHODS: In a prospective cohort of women with AF, regression analyses were conducted to assess the relationship between low-voltage area (LVA) and sex hormone levels. CREM-IbΔC-X mice, a spontaneous AF model, underwent bilateral ovariectomy (OVX). Electrocardiograms, echocardiograms, and Masson staining were performed. Follicle-stimulating hormone (FSH) stimulation was applied in male mice for 3 months. OVX was also applied in an angiotensin II (Ang II)-induced pressure overload mouse model, after programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms. RESULTS: Women demonstrated a significantly higher LVA burden than men (P < .001). A positive correlation was observed between LVA burden and FSH level (P = .002). Mice in the OVX group exhibited a significantly higher incidence of AF (P = .040) and atrial fibrosis (P = .021) compared with the Sham group, which could be attenuated by adeno-associated virus encoding small interfering RNA against Fshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P = .035) and atrial fibrosis (P = .002). In Ang II-induced female mice, OVX prompted atrial fibrosis, increased AF inducibility, and shortened atrial effective refractory period, which could be attenuated with knockdown of Fshr. RNA-seq indicated mitochondrial dysfunction. CONCLUSION: Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.

6.
J Arrhythm ; 40(4): 839-848, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139906

RESUMEN

Background: Laser balloon (LB) pulmonary vein isolation (PVI) is an established ablation technique for atrial fibrillation (AF). We report long-term follow-up and procedural data of LB-PVI and we compare the first and second LB generation. Methods: Patients undergoing LB ablation with first- (LB1) or second-generation LB (LB2) for AF were retrospectively enrolled and divided into two groups. Procedural endpoint was complete PVI. Clinical success was defined as no recurrence of AF/atrial tachycardia after a 90 days blanking period. Results: 538 patients were included (age 66 ± 10 years, 58% paroxysmal AF), 427 in LB1 and 111 in LB2. 2079 PVs were targeted and 2073 (99.7%) were successfully isolated; 2027 (97.5%) using solely the LB. Additional touch-up ablation was limited (46 PVs; 2.2%) with no difference between the groups. Procedural (LB1: 120 ± 33 minutes vs. LB2: 99 ± 22 min; p < .001) and fluoroscopy time (LB1: 11.2 ± 5 min vs. LB2: 8.5 ± 3 min; p < .001) were shorter with LB2. The complication rate was 8.9% (LB1: 10.1% vs. LB2: 4.5%; p = .067) with most complications resulting from the access site (21/48). Overall freedom from AF after 1-year was 73.7% (paroxysmal AF: 76.9%; persistent AF: 69.3%; p < .001) with no difference between the groups (LB1: 73.4% vs. LB2: 74.7%; p = .491). Conclusion: LB showed a high efficacy and acceptable safety, with numerically lower complication rates with the second-generation LB. Procedure and fluoroscopy times were shorter with LB2. Overall, 73.7% of patients were free from AF at 1-year, with comparable results among both generations.

9.
Int Immunopharmacol ; 138: 112517, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38924866

RESUMEN

Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.


Asunto(s)
Apoptosis , Movimiento Celular , Melanoma , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Quercetina , Transducción de Señal , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos
10.
Int Immunopharmacol ; 134: 112261, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38761783

RESUMEN

BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.


Asunto(s)
Antiinflamatorios , Citocinas , Modelos Animales de Enfermedad , Flavonoides , Glucósidos , Células HaCaT , Imiquimod , Queratinocitos , Lipopolisacáridos , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos BALB C , Psoriasis , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/inducido químicamente , Psoriasis/patología , Ratones , Humanos , Células RAW 264.7 , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Flavonoides/farmacología , Flavonoides/uso terapéutico , Citocinas/metabolismo , Queratinocitos/efectos de los fármacos , Glucósidos/uso terapéutico , Glucósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Piel/patología , Piel/efectos de los fármacos , Piel/inmunología , Proliferación Celular/efectos de los fármacos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Dermatitis/tratamiento farmacológico , Dermatitis/patología , Dermatitis/inmunología , Línea Celular
11.
J Cardiovasc Electrophysiol ; 35(7): 1412-1421, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750671

RESUMEN

BACKGROUND: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. METHODS: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body-weight-reduction underwent CBA. RESULTS: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch-up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real-time-isolation (78.6% vs. 78.5%), single-shot-isolation (86.5% vs. 88.8%), but significantly longer time-to-sustained-isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture-site-complication (6.9% vs. 1.6%) in Group A. One-year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re-Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089). CONCLUSION: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.


Asunto(s)
Fibrilación Atrial , Índice de Masa Corporal , Criocirugía , Estudios de Factibilidad , Obesidad , Venas Pulmonares , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Criocirugía/efectos adversos , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Anciano , Factores de Riesgo , Factores de Tiempo , Obesidad/diagnóstico , Obesidad/complicaciones , Obesidad/fisiopatología , Venas Pulmonares/cirugía , Venas Pulmonares/fisiopatología , Frecuencia Cardíaca , Índice de Severidad de la Enfermedad , Potenciales de Acción , Estudios Retrospectivos , Recurrencia
12.
Adv Mater ; 36(29): e2400115, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38752837

RESUMEN

All-solid-state lithium metal batteries (ASSLMBs) are considered as the most promising candidates for the next-generation high-safety batteries. To achieve high energy density in ASSLMBs, it is essential that the solid-state electrolytes (SSEs) are lightweight, thin, and possess superior electrochemical stability. In this study, a feasible and scalable fabrication approach to construct 3D supporting skeleton using an electro-blown spinning technique is proposed. This skeleton not only enhances the mechanical strength but also hinders the migration of Li-salt anions, improving the lithium-ion transference number of the SSE. This provides a homogeneous distribution of Li-ion flux and local current density, promoting uniform Li deposition. As a result, based on the mechanically robust and thin SSEs, the Li symmetric cells show outstanding Li plating/stripping reversibility. Besides, a stable interface contact between SSE and Li anode has been established with the formation of an F-enriched solid electrolyte interface layer. The solid-state Li|sulfurized polyacrylonitrile (Li|SPAN) cell achieves a capacity retention ratio of 94.0% after 350 cycles at 0.5 C. Also, the high-voltage Li|LCO cell shows a capacity retention of 92.4% at 0.5 C after 500 cycles. This fabrication approach for SSEs is applicable for commercially large-scale production and application in high-energy-density and high-safety ASSLMBs.

14.
J Interv Card Electrophysiol ; 67(5): 1247-1255, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38573537

RESUMEN

BACKGROUND: Vascular complications are a common occurrence during atrial fibrillation ablation. Observational studies indicate that the utilization of ultrasound (US)-guided puncture may decrease the incidence of vascular complications; however, its routine use is not established in many centres. METHODS: Patients undergoing catheter ablation for atrial fibrillation were included sequentially. All patients receiving US-guided punctures were prospectively enrolled (US group), while patients who underwent the procedure with standard puncture technique served as control group (No-US group). Periprocedural vascular complications requiring intervention within 30 days of the procedure were defined as the primary endpoint. RESULTS: A total of 599 patients (average age: 69 ± 11 years, 62.9% male) were analysed. The incidence of vascular complications was lower with the US-guided puncture than with the anatomic landmark-guided puncture (14/299 [4.7%] vs. 27/300 [9%], p = 0.036). The US-guided vascular access significantly reduced the rate of false aneurysms (3/299 [1%] vs. 12/300 [4%], p = 0.019). In addition, the occurrence of arteriovenous fistula (2/299 [0.7%] vs. 4/300 [1.3%], p = 0.686) and haematoma requiring treatment (9/299 [3%] vs. 11/300 [3.7%], p = 0.655) were also lower in the US group. US-guided puncture did not prolong the procedure time (mean procedure time: 57.48 ± 24.47 min vs. 56.09 ± 23.36 min, p = 0.478). Multivariate regression analysis identified female gender (OR 2.079, CI 95% 1.096-3.945, p = 0.025) and conventional vascular access (OR 2.079, CI 95% 1.025-3.908, p = 0.042) as predictors of vascular complications. CONCLUSIONS: The implementation of US-guided vascular access for left atrial catheter ablation resulted in a significant decrease of the overall vascular complication rate.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Ultrasonografía Intervencional , Humanos , Masculino , Femenino , Ablación por Catéter/métodos , Fibrilación Atrial/cirugía , Fibrilación Atrial/diagnóstico por imagen , Anciano , Ultrasonografía Intervencional/métodos , Hospitales de Alto Volumen , Estudios Prospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Punciones , Incidencia , Persona de Mediana Edad
16.
Nano Lett ; 24(17): 5292-5300, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38648075

RESUMEN

Understanding the structure-property relationship of lithium-ion conducting solid oxide electrolytes is essential to accelerate their development and commercialization. However, the structural complexity of nonideal materials increases the difficulty of study. Here, we develop an algorithmic framework to understand the effect of microstructure on the properties by linking the microscopic morphology images to their ionic conductivities. We adopt garnet and perovskite polycrystalline oxides as examples and quantify the microscopic morphologies via extracting determined physical parameters from the images. It directly visualizes the effect of physical parameters on their corresponding ionic conductivities. As a result, we can determine the microstructural features of a Li-ion conductor with high ionic conductivity, which can guide the synthesis of highly conductive solid electrolytes. Our work provides a novel approach to understanding the microstructure-property relationship for solid-state ionic materials, showing the potential to extend to other structural/functional ceramics with various physical properties in other fields.

17.
Cancer Lett ; 590: 216840, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38604311

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, highlighting the urgent need to elucidate the underlying oncogenic mechanisms. VIRMA is a classic isoform of methyltransferases that participates in epigenetic transcriptomic modification in eukaryotic mRNAs. However, the exact roles of VIRMA in PDAC remain unclear. Here, we identified that VIRMA is highly expressed in PDAC, and histone modifications of the promoter may partly account for this dysregulation. Moreover, VIRMA is closely related to glycolysis and poor prognosis in PDAC. We further determined that STRA6 is a direct downstream target of VIRMA in PDAC by RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq). VIRMA is involved in gene expression regulation via 3' UTR targeting of STRA6 mRNA. Furthermore, the m6A reader IGF2BP2 was shown to critically contribute to the stability of STRA6 mRNA. We describe the role of VIRMA in promoting signaling via the STRA6/STAT3 axis, which results in increased levels of HIF-1α, a key activator of glycolysis. In vivo and in vitro experiments reveal that the VIRMA-STRA6-STAT3-HIF-1α axis plays an instrumental role in glycolysis and tumor progression in PDAC. In conclusion, we demonstrate that VIRMA can increase glycolysis in PDAC by upregulating STRA6, a cell surface membrane protein that stimulates the STAT3 pathway, thereby activating HIF-1α and leading to pancreatic cancer malignancy. Overall, our data strongly suggest that the VIRMA-STRA6-STAT3-HIF-1α axis is a viable therapeutic target in PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Regulación Neoplásica de la Expresión Génica , Glucólisis , Neoplasias Pancreáticas , Regulación hacia Arriba , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Glucólisis/genética , Línea Celular Tumoral , Animales , Progresión de la Enfermedad , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Masculino , Ratones Desnudos , Transducción de Señal
18.
Sci Rep ; 14(1): 5816, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461337

RESUMEN

The classroom video has a complex background and dense targets. This study utilizes small object detection technology to analyze and evaluate students' behavior in the classroom, aiming to objectively and accurately assess classroom quality. Firstly, noise is removed from the images using a median filter, and the contrast of the images is enhanced through histogram equalization. Label smoothing is applied to reduce the model's sensitivity to labels. Then, features are extracted from the preprocessed images, and multi-scale feature fusion is employed to enhance semantic expression across multiple scales. Finally, a combination loss function is utilized to improve the accuracy of multi-object recognition tasks. Real-time detection of students' behaviors in the classroom is performed based on the small object detection model. The average head-up rate in the classroom is calculated, and the quality of teaching is evaluated and analyzed. This study explores the methods and applications of small object detection technology based on actual teaching cases and analyzes and evaluates its effectiveness in evaluating the quality of higher education classroom teaching. The research findings demonstrate the significant importance of small object detection technology in effectively evaluating students' learning conditions in higher education classrooms, leading to improved teaching quality and personalized education.

19.
Cancer Lett ; 588: 216784, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38458594

RESUMEN

Glycolytic metabolism is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and tumor-associated stromal cells play important roles in tumor metabolism. We previously reported that tumor-associated macrophages (TAMs) facilitate PDAC progression. However, little is known about whether TAMs are involved in regulating glycolysis in PDAC. Here, we found a positive correlation between CD68+ TAM infiltration and FDG maximal standardized uptake (FDG SUVmax) on PET-CT images of PDAC. We discovered that the glycolytic gene set was prominently enriched in the high TAM infiltration group through Gene Set Enrichment Analysis using The Cancer Genome Atlas database. Mechanistically, TAMs secreted IL-8 to promote GLUT3 expression in PDAC cells, enhancing tumor glycolysis both in vitro and in vivo, whereas this effect could be blocked by the IL-8 receptor inhibitor reparixin. Furthermore, IL-8 promoted the translocation of phosphorylated STAT3 into the nucleus to activate the GLUT3 promoter. Overall, we demonstrated that TAMs boosted PDAC cell glycolysis through the IL-8/STAT3/GLUT3 signaling pathway. Our cumulative findings suggest that the abrogation of TAM-induced tumor glycolysis by reparixin might exhibit an antitumor impact and offer a potential therapeutic target for PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sulfonamidas , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Transportador de Glucosa de Tipo 3/genética , Transportador de Glucosa de Tipo 3/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Fluorodesoxiglucosa F18/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Macrófagos/metabolismo , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Transducción de Señal , Glucólisis , Línea Celular Tumoral , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
20.
J Cancer Res Clin Oncol ; 150(3): 127, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38483604

RESUMEN

PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.


Asunto(s)
Neoplasias Pancreáticas , Humanos , Biomarcadores , Glucógeno Fosforilasa de Forma Encefálica/genética , Glucógeno Fosforilasa de Forma Encefálica/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Pronóstico , Transducción de Señal/genética
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