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1.
PLoS One ; 19(7): e0305529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38995974

RESUMEN

This study investigates the thermal conductivity (λ) and volumetric heat capacity (C) of sandy soil samples under a variety of conditions, including freeze-thaw cycles at temperatures both above and below zero and differing moisture levels. To estimate these thermal properties, a novel predictive model, EFAttNet, was developed, which utilizes custom-designed embedding and attention-based fusion networks. When compared to traditional de Vries empirical models and other baseline algorithms, EFAttNet demonstrated superior accuracy. Preliminary measurements showed that λ values increased linearly with moisture content but decreased with temperature, whereas C values exhibited a rising trend with both moisture content and freezing temperature. Following freeze-thaw cycles, both λ and C were positively influenced by moisture content and freezing temperature. The EFAttNet-based model proved highly accurate in predicting thermal properties, particularly effective at capturing nonlinear relationships among the influencing factors. Among these factors, the degree of saturation had the most significant impact, followed by the number of freeze-thaw cycles, subzero temperatures, porosity, and moisture content. Notably, dry density exerted minimal influence on thermal properties, likely due to the overriding effects of other factors or specific soil characteristics, such as particle size distribution or mineralogical composition. These findings have significant implications for construction and engineering projects, especially in terms of sustainability and energy efficiency. The demonstrated accuracy of the EFAttNet-based model in estimating thermal properties under various conditions holds promise for practical applications. Although focused on specific soil types and conditions, the insights gained can guide further research and development in managing soil thermal properties across diverse environments, thereby enhancing our understanding and application in this field.


Asunto(s)
Congelación , Suelo , Suelo/química , Algoritmos , Conductividad Térmica , Modelos Teóricos , Temperatura
2.
J Autism Dev Disord ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017804

RESUMEN

PURPOSE: Previous researches suggest that social robots can facilitate the learning of children with Autism Spectrum Disorder (ASD) by enhancing their interests, engagement, and attention. However, there is limited understanding regarding whether children with ASD can learn directly from the testimony of social robots and whether they can remain vigilant based on the perceived accuracy of these robots. Therefore, the present study was conducted to examine whether children with ASD demonstrated selective trust towards social robots. METHODS: Twenty-nine children with ASD between ages of 4-7 years, and 38 typically-developing (TD) age and IQ-matched peers participated in classic selective trust tasks. During the tasks, they learned the names of novel objects from either a pair of social robots or a pair of human informants, where one informant had previously been established as accurate and the other inaccurate. RESULTS: Children with ASD trusted information from an accurate social robot over an inaccurate one, similar to their performance with human informants. However, compared to TD children, children with ASD exhibited lower levels of selective trust regardless of the type of informants they learned from. CONCLUSIONS: Our study suggests that children with ASD can selectively trust and acquire knowledge from social robots, shedding light on the potential use of social robots in supporting individuals with ASD.

3.
Opt Lett ; 49(14): 3950-3953, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008748

RESUMEN

A 3 × 3 coupler multiphase demodulation scheme is proposed to eliminate the impact of working point drifting and the laser relative intensity noise (RIN) on a 3 × 3 coupler interferometric system. An ellipse-fitting algorithm (EFA) is applied to fit the two interference signals of the 3 × 3 coupler in order, then the ATAN algorithm is applied to obtain three noise-containing signals with specific trigonometric relationships. By averaging the three signals, the demodulated phase noise induced from RIN can be effectively eliminated. The experimental results show that compared with the asymmetric demodulation scheme without intensity noise control, the noise floor of the proposed scheme decreases from 4.5 to 1 µrad/√Hz at 1 kHz and 2.7 to 0.8 µrad/√Hz at 3 kHz. At high frequencies, the average noise floor level is reduced from 10 to 0.9 µrad/√Hz, a reduction of about 21 dB. Furthermore, the variation range of the average noise floor is reduced from 5.4 to 0.17 µrad /√Hz within 100 s.

4.
Ophthalmology ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972357

RESUMEN

PURPOSE: To investigate the myopia control efficacy of novel Lenslet-ARray-Integrated (LARI) spectacle lenses with positive (PLARI) and negative (NLARI) power lenslets worn for one year in myopic children. DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: A total of 240 children, aged 6 to 12 years, with spherical equivalent refraction (SER) between -4.00 and -1.00 diopter (D), astigmatism of 1.50 D or less, and anisometropia of 1.00 D or less. METHODS: Participants were assigned randomly in a 1:1:1 ratio to PLARI, NLARI, and a control (single-vision (SV)) groups. Cycloplegic autorefraction and axial length were measured at baseline and 6-month intervals after lens wear. MAIN OUTCOME MEASURES: Changes in SER, axial elongation (AE), and differences between groups. RESULTS: After 1-year, SER changes and AE in the PLARI and NLARI groups were significantly less than those in the SV group (SER: -0.30 ± 0.48 D, -0.21 ± 0.35 D, -0.66 ± 0.40 D; AE: 0.19 ± 0.20 mm, 0.17 ± 0.14 mm, 0.34 ± 0.18 mm, respectively) (all P < 0.001). There were no significant differences in SER changes and AE between PLARI and NLARI groups (P = 0.54 and P = 1.00, respectively). Younger age was associated with more rapid SER increase and larger AE in the SV (r = 0.40, P < 0.001 and r = -0.59, P < 0.001, respectively) and PLARI (r= 0.46, P < 0.001 and r = -0.52, P < 0.001, respectively) groups, but not in the NLARI group (r = -0.002, P = 0.98 and r = -0.08, P = 0.48, respectively). CONCLUSIONS: Compared with the SV group, both PLARI and NARI groups showed significantly slower myopia progression in terms of SER and axial elongation. Faster myopia progression, in terms of both SER and AE, was associated with younger age in the SV and PLARI groups, but not in the NLARI group.

5.
Neural Netw ; 179: 106533, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39079378

RESUMEN

The increasing size of pre-trained language models has led to a growing interest in model compression. Pruning and distillation are the primary methods employed to compress these models. Existing pruning and distillation methods are effective in maintaining model accuracy and reducing its size. However, they come with limitations. For instance, pruning is often suboptimal and biased by transforming it into a continuous optimization problem. Distillation relies primarily on one-to-one layer mappings for knowledge transfer, which leads to underutilization of the rich knowledge in teacher. Therefore, we propose a method of joint pruning and distillation for automatic pruning of pre-trained language models. Specifically, we first propose Gradient Progressive Pruning (GPP), which achieves a smooth transition of indicator vector values from real to binary by progressively converging the values of unimportant units' indicator vectors to zero before the end of the search phase. This effectively overcomes the limitations of traditional pruning methods while supporting compression with higher sparsity. In addition, we propose the Dual Feature Distillation (DFD). DFD adaptively globally fuses teacher features and locally fuses student features, and then uses the dual features of global teacher features and local student features for knowledge distillation. This realizes a "preview-review" mechanism that can better extract useful information from multi-level teacher information and transfer it to student. Comparative experiments on the GLUE benchmark dataset and ablation experiments indicate that our method outperforms other state-of-the-art methods.

6.
Vet Microbiol ; 296: 110175, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39018941

RESUMEN

Mycoplasma gallisepticum (MG) is the primary causative agent of chronic respiratory disease (CRD) in chickens, characterized by respiratory inflammation. S100A9 plays a pivotal role in modulating the inflammatory response to microbial pathogens. Our prior investigation revealed a significant upregulation of S100A9 in the lungs of chickens following MG infection. This study delves into the immunomodulatory effects of S100A9 during MG infection, demonstrating a notable increase in S100A9 levels in the lungs, immune organs, alveolar epithelial type II cells (AECII), and macrophage HD11 cells of MG-infected chicks and embryos. In MG-infected AECII cells, S100A9 overexpression significantly enhanced MG proliferation and adhesion, suppressed AVBD1, NFκB, pro-inflammatory factors (IL1ß and TNFα), and chemokines, reduced apoptosis, and promoted cell proliferation, thereby facilitating MG infection. Conversely, inhibiting S100A9 produced opposing effects. In MG-infected HD11 cells, S100A9 impeded MG proliferation and adhesion, increased AVBD1, NFκB, pro-inflammatory factors, and chemokines, and induced cell apoptosis while inhibiting proliferation. Additional results demonstrated that S100A9 facilitates MG infection by modulating the TLR7/NFκB/JAK/STAT pathway in AECII/HD11 cells. In summary, S100A9 exhibits a dual role in activating/inhibiting the natural immune response through TLR7/NFκB/JAK/STAT pathway regulation. This dual role promotes MG infection in AECII cells while enabling MG to evade immune surveillance by HD11 cells, ultimately enhancing the overall infection process. These findings advance our understanding of host-pathogen interactions during MG infection and underscore S100A9's potential as a therapeutic target for CRD in chickens.

9.
J Intell ; 12(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38921693

RESUMEN

The prevalence of media multitasking has raised concerns regarding its potential impact on cognitive abilities. Despite increasing attention given to this topic, there remains no consensus on how media multitasking is related to cognitive performance. This study aims to shed light on this issue by examining whether and how personality traits and family socioeconomic status (SES) moderate the relationship between media multitasking and reasoning performance. To this end, a large sample of university students (n = 777) completed a battery of measures, including the Raven's Advanced Progressive Matrices, the Media Multitasking Inventory, the Big Five Inventory, the Barratt Impulsiveness Scale, the Grit Scale, and the Family SES Questionnaire. Results revealed a negative correlation between media multitasking and reasoning performance. However, this relationship was substantially moderated by conscientiousness, extraversion, openness, and family SES. Specifically, media multitasking was more detrimental to reasoning performance among individuals with lower levels of conscientiousness, extraversion, openness, and family SES, whereas it was less detrimental to counterparts with higher levels of these personality traits and family SES. The proposed moderation model, for the first time, not only offers novel insights into the theoretical accounts regarding how media multitasking relates to cognitive abilities, but also identifies the protective factors that may buffer the negative impacts of media multitasking.

10.
J Cancer Res Clin Oncol ; 150(6): 300, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850373

RESUMEN

PURPOSE: Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes. METHODS: We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods. RESULTS: Overall survival differed significantly between the training and validation cohorts' low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors. CONCLUSION: The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.


Asunto(s)
Linfocitos T CD8-positivos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Estructuras Linfoides Terciarias , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Pronóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Linfocitos T CD8-positivos/inmunología , Estructuras Linfoides Terciarias/genética , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Genómica/métodos , Masculino , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Anciano
11.
Math Biosci ; 374: 109239, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906526

RESUMEN

Recent studies have utilized evolutionary mechanisms to impede the emergence of drug-resistant populations. In this paper, we develop a mathematical model that integrates hormonal treatment, immunotherapy, and the interactions among three cell types: drug-sensitive cancer cells, drug-resistant cancer cells and immune effector cells. Dynamical analysis is performed, examining the existence and stability of equilibria, thereby confirming the model's interpretability. Model parameters are calibrated using available prostate cancer data and literature. Through bifurcation analysis for drug sensitivity under different immune effector cells recruitment responses, we find that resistant cancer cells grow rapidly under weak recruitment response, maintain at a low level under strong recruitment response, and both may occur under moderate recruitment response. To quantify the competitiveness of sensitive and resistant cells, we introduce the comprehensive measures R1 and R2, respectively, which determine the outcome of competition. Additionally, we introduce the quantitative indicators CIE1 and CIE2 as comprehensive measures of the immune effects on sensitive and resistant cancer cells, respectively. These two indicators determine whether the corresponding cancer cells can maintain at a low level. Our work shows that the immune system is an important factor affecting the evolution of drug resistance and provides insights into how to enhance immune response to control resistance.


Asunto(s)
Resistencia a Antineoplásicos , Humanos , Resistencia a Antineoplásicos/inmunología , Masculino , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/tratamiento farmacológico , Modelos Biológicos , Inmunoterapia/métodos , Dinámicas no Lineales , Conceptos Matemáticos
12.
Surg Endosc ; 38(8): 4505-4511, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914886

RESUMEN

OBJECTIVE: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. METHODS: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. RESULTS: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). CONCLUSION: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method.


Asunto(s)
Pancreatitis Aguda Necrotizante , Irrigación Terapéutica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Irrigación Terapéutica/métodos , Pancreatitis Aguda Necrotizante/cirugía , Pancreatitis Aguda Necrotizante/sangre , Proteína C-Reactiva/análisis , Anciano , Endoscopía del Sistema Digestivo/métodos , Recuento de Leucocitos , Polipéptido alfa Relacionado con Calcitonina/sangre
13.
Appl Immunohistochem Mol Morphol ; 32(5): 244-248, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38712587

RESUMEN

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Cerebelosas , Hemangioblastoma , Neoplasias Renales , Enfermedad de von Hippel-Lindau , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/diagnóstico , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/secundario , Hemangioblastoma/patología , Hemangioblastoma/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/diagnóstico , Metástasis de la Neoplasia , Enfermedad de von Hippel-Lindau/patología , Enfermedad de von Hippel-Lindau/diagnóstico
14.
Artículo en Inglés | MEDLINE | ID: mdl-38779800

RESUMEN

Background: Leech bites have long been a persistent problem for individuals engaged in outdoor activities, particularly in environments such as moors, jungles, and grasslands. Methods to prevent leech bites are anecdotal and individual, highlighting the need for the development of universal and effective repellent formulations. This study developed a novel approach for repelling leeches using combined repellent agents and a film-forming material (polyvinyl butyral), to enhance efficiency in multi-scenario applications. Material and methods: This study demonstrates that citronellal, icaridin and DDAC (didecyl dimethyl ammonium chloride) showcasing active avoidance and contact toxicity on leeches. the optimized repellent formulation (MSRS, containing citronellal, icaridin and DDAC as repellent agents) enables specific sustained release properties of constituents in both air and water conditions. Results: MSRS could effectively achieve the purposes of "proactive repelling", "contact repelling", and "bite detaching". The effectiveness could last for several hours. Additionally, the hydrophobic polyvinyl butyral membrane reduced the transdermal absorption of repellent agents. Moreover, the formulation is biocompatible and environmentally friendly. Conclusions: This study provides a new feasible strategy for the prevention and removal of leech bites.

15.
Neuroendocrinology ; 114(6): 589-601, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38565081

RESUMEN

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.


Asunto(s)
Tumores Neuroendocrinos , Vía de Señalización Wnt , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Ratas , Adenoma/metabolismo , Adenoma/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Ratones Desnudos , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Vía de Señalización Wnt/fisiología , Vía de Señalización Wnt/efectos de los fármacos
16.
Adv Anat Pathol ; 31(4): 265-270, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38627880

RESUMEN

Primary gastric leiomyosarcoma is an exceptionally rare disease. This review covers 41 post-gastrointestinal stromal tumor (GIST) era gastric leiomyosarcoma cases that are supported by immunohistochemistry markers. Other spindle cell lesions are also excluded through histological and immunohistochemistry evaluations. The patients range from 3 to 82 years old, with an average age of 54.6 years. The male-to-female ratio is 1.4:1, from diverse geographic areas. Patients may experience abdominal symptoms, and tumor sizes vary between 1 cm and 22 cm. Morphologically, tumors originate from the muscularis propria or the muscularis mucosae, well-circumscribed with spindle cells arranged in fascicule. Tumoral cells exhibit positivity for smooth muscle markers while being negative for GIST markers and others. The mitotic index ranges from 2 to 500/50 high power field. Ki-67 index varies from 15% to 70%. Management typically involves gastrectomy and other appropriate treatments, with tumor recurrence being uncommon. 56% of patients are alive, with 5 patients dying from this disease. Statistical analyses conducted on post-GIST era cases reveal that a mitotic index of ≥100/50 high power field, tumor recurrence, metastasis, or positive lymph nodes significantly correlate with prognosis.


Asunto(s)
Tumores del Estroma Gastrointestinal , Leiomiosarcoma , Neoplasias Gástricas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Tumores del Estroma Gastrointestinal/patología , Leiomiosarcoma/patología , Neoplasias Gástricas/patología , Preescolar , Niño , Adolescente , Adulto Joven , Adulto
17.
Proc (Bayl Univ Med Cent) ; 37(3): 403-407, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628324

RESUMEN

Background: Diagnosing atypical glandular cells (AGC) is a significant challenge in cytomorphology. Methods: A retrospective study was undertaken to assess the prevalence of AGC and the subsequent histological outcomes over 5 years at a single institution. Results: A total of 159,649 ThinPrep Pap tests, including 395 cases of AGC, were retrieved, of which 330 AGC cases had follow-up histopathology. Among these 330 cases, 43.9% were classified as AGC not otherwise specified, followed by AGC-endocervical cells at 33.3%. The most frequently observed histological findings at follow-up included CIN1 and benign mucosa with reactive changes, followed by high-grade squamous intraepithelial lesion and cervical squamous cell carcinoma. The overall 5-year insignificant AGC rate was 0.12%, and the overall 5-year significant AGC rate was 0.08%. Notably, 36.7% of AGC cases tested positive for high-risk human papillomavirus. Interestingly, the level of experience did not significantly impact the rates for significant or insignificant AGC diagnosis. However, senior cytopathologists had a higher AGC report rate compared to their junior peers. Conclusion: The AGC diagnostic rate at our institution falls within the range given by the College of American Pathologists. A significant number of cases had follow-up histologic results available, and the overall 5-year insignificant AGC rate was 0.12%.

18.
Biomed Pharmacother ; 174: 116470, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565061

RESUMEN

ERCC2 plays a pivotal role in DNA damage repair, however, its specific function in cancer remains elusive. In this study, we made a significant breakthrough by discovering a substantial upregulation of ERCC2 expression in glioblastoma (GBM) tumor tissue. Moreover, elevated levels of ERCC2 expression were closely associated with poor prognosis. Further investigation into the effects of ERCC2 on GBM revealed that suppressing its expression significantly inhibited malignant growth and migration of GBM cells, while overexpression of ERCC2 promoted tumor cell growth. Through mechanistic studies, we elucidated that inhibiting ERCC2 led to cell cycle arrest in the G0/G1 phase by blocking the CDK2/CDK4/CDK6/Cyclin D1/Cyclin D3 pathway. Notably, we also discovered a direct link between ERCC2 and CDK4, a critical protein in cell cycle regulation. Additionally, we explored the potential of TRAIL, a low-toxicity death ligand cytokine with anticancer properties. Despite the typical resistance of GBM cells to TRAIL, tumor cells undergoing cell cycle arrest exhibited significantly enhanced sensitivity to TRAIL. Therefore, we devised a combination strategy, employing TRAIL with the nanoparticle DMC-siERCC2, which effectively suppressed the GBM cell proliferation and induced apoptosis. In summary, our study suggests that targeting ERCC2 holds promise as a therapeutic approach to GBM treatment.


Asunto(s)
Puntos de Control del Ciclo Celular , Proliferación Celular , Glioblastoma , Nanopartículas , Ligando Inductor de Apoptosis Relacionado con TNF , Proteína de la Xerodermia Pigmentosa del Grupo D , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Humanos , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacos , Nanopartículas/química , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Proliferación Celular/efectos de los fármacos , Proteína de la Xerodermia Pigmentosa del Grupo D/metabolismo , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Animales , Apoptosis/efectos de los fármacos , Ratones Desnudos , Masculino
19.
World J Clin Cases ; 12(11): 1900-1908, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38660542

RESUMEN

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT. This review elucidates the risks, mechanisms, reliable markers, and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

20.
Redox Biol ; 72: 103115, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38554522

RESUMEN

BACKGROUND: Premature infants often require oxygen supplementation, which can elicit bronchopulmonary dysplasia (BPD) and lead to mitochondrial dysfunction. Mitochondria play important roles in lung development, in both normal metabolism and apoptosis. Enhancing our comprehension of the underlying mechanisms in BPD development can facilitate the effective treatments. METHODS: Plasma samples from BPD and non-BPD infants were collected at 36 weeks post-menstrual age and used for metabolomic analysis. Based on hyperoxia-induced animal and cell models, changes in mitophagy and apoptosis were evaluated following treatment with itaconic acid (ITA). Finally, the mechanism of action of ITA in lung development was comprehensively demonstrated through rescue strategies and administration of corresponding inhibitors. RESULTS: An imbalance in the tricarboxylic acid (TCA) cycle significantly affected lung development, with ITA serving as a significant metabolic marker for the outcomes of lung development. ITA improved the morphological changes in BPD rats, promoted SP-C expression, and inhibited the degree of alveolar type II epithelial cells (AEC II) apoptosis. Mechanistically, ITA mainly promotes the nuclear translocation of transcription factor EB (TFEB) to facilitate dysfunctional mitochondrial clearance and reduces apoptosis in AEC II cells by regulating autophagic flux. CONCLUSION: The metabolic imbalance in the TCA cycle is closely related to lung development. ITA can improve lung development by regulating autophagic flux and promote the nuclear translocation of TFEB, implying its potential therapeutic utility in the treatment of BPD.


Asunto(s)
Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Displasia Broncopulmonar , Hiperoxia , Succinatos , Succinatos/farmacología , Animales , Autofagia/efectos de los fármacos , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/patología , Ratas , Humanos , Hiperoxia/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Ciclo del Ácido Cítrico/efectos de los fármacos , Femenino , Mitofagia/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Recién Nacido
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