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1.
J Environ Sci (China) ; 146: 198-216, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38969448

RESUMEN

Many waterborne diseases are related with viruses, and COVID-19 worldwide has raised the concern of virus security in water into the public horizon. Compared to other conventional water treatment processes, membrane technology can achieve satisfactory virus removal with fewer chemicals, and prevent the outbreaks of viruses to a maximal extent. Researchers developed new modification methods to improve membrane performance. This review focused on the membrane modifications that enhance the performance in virus removal. The characteristics of viruses and their removal by membrane filtration were briefly generalized, and membrane modifications were systematically discussed through different virus removal mechanisms, including size exclusion, hydrophilic and hydrophobic interactions, electronic interactions, and inactivation. Advanced functional materials for membrane modification were summarized based on their nature. Furthermore, it is suggested that membranes should be enhanced through different mechanisms mainly based on their ranks of pore size. The current review provided theoretical support regarding membrane modifications in the enhancement of virus removal and avenues for practical application.


Asunto(s)
Filtración , Membranas Artificiales , Purificación del Agua , Purificación del Agua/métodos , Filtración/métodos , Virus , COVID-19 , SARS-CoV-2 , Microbiología del Agua
2.
Front Hum Neurosci ; 18: 1356483, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974479

RESUMEN

Reading is vital for acquiring knowledge and studies have demonstrated that phonology-focused interventions generally yield greater improvements than meaning-focused interventions in English among children with reading disabilities. However, the effectiveness of reading instruction can vary among individuals. Among the various factors that impact reading skills like reading exposure and oral language skills, reading instruction is critical in facilitating children's development into skilled readers; it can significantly influence reading strategies, and contribute to individual differences in reading. To investigate this assumption, we developed a computational model of reading with an optimised MikeNet simulator. In keeping with educational practices, the model underwent training with three different instructional methods: phonology-focused training, meaning-focused training, and phonology-meaning balanced training. We used semantic reliance (SR), a measure of the relative reliance on print-to-sound and print-to-meaning mappings under the different training conditions in the model, as an indicator of individual differences in reading. The simulation results demonstrated a direct link between SR levels and the type of reading instruction. Additionally, the SR scores were able to predict model performance in reading-aloud tasks: higher SR scores were correlated with increased phonological errors and reduced phonological activation. These findings are consistent with data from both behavioral and neuroimaging studies and offer insights into the impact of instructional methods on reading behaviors, while revealing individual differences in reading and the importance of integrating OP and OS instruction approaches for beginning readers.

3.
Nanoscale ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979693

RESUMEN

Atomically ordered intermetallic compounds (IMCs) have been extensively studied for exploring catalysts with high activity, selectivity, and longevity. Compared to random alloys, IMCs present a more pronounced geometric and electronic effect with desirable catalytic performance. Their well-defined structure makes IMCs ideal model catalysts for studying the catalytic mechanism. This review focuses especially on elemental composition, electron transfer, and structure/phase evolution under high temperature treatment conditions, providing direct evidence for the migration and rearrangement of metal atoms through electron microscopy. We then present the outstanding applications of IMCs in growing single-walled nanotubes, hydrogenation/dehydrogenation reactions, and electrocatalysis from the perspective of electronic, geometric, strain, and bifunctional effects of ordered IMCs. Finally, the current obstacles associated with the use of in situ techniques are proposed, as well as future research possibilities.

4.
J Agric Food Chem ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965062

RESUMEN

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver ß-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

5.
J Hum Genet ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982179

RESUMEN

Endometriosis is a common gynecological disorder affecting around 10% of reproductive-age women. Although many hypotheses were proposed, genetic alteration has been considered as one of the key factors promoting pathogenesis. Due to racial/ethnic disparities in the process of hormone regulation and nutrition metabolism, a genome-wide association study (GWAS) with 2794 cases and 27,940 controls was conducted in a Taiwanese-Han population. Our study identified five significant susceptibility loci for endometriosis, and three of them, WNT4 (on the 1p36.12), RMND1 (6q25.1), and CCDC170 (6q25.1), have been previously associated with endometriosis across different populations, including European and Japanese descent cohorts. Other two including C5orf66/C5orf66-AS2 (5q31.1) and STN1 (10q24.33) are newly identified ones. Functional network analysis of potent risk genes revealed the involvement of cancer susceptibility and neurodevelopmental disorders in endometriosis development. In addition, long non-coding RNAs (lncRNAs) C5orf66 and C5orf66-AS2 can interact with many RNA-binding proteins (RBPs) which can influence RNA metabolic process, mRNA stabilization, and mRNA splicing, leading to dysregulation in tumor-promoting gene expression. Those findings support clinical observations of differences in the presentation of endometriosis in Taiwanese-Han population with higher risks of developing deeply infiltrating/invasive lesions and the associated malignancies.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38953943

RESUMEN

INTRODUCTION: Length of stay (LOS) has been extensively assessed as a marker for healthcare utilization, functional outcomes, and cost of care for patients undergoing arthroplasty. The notable patient-to-patient variation in LOS following revision hip and knee total joint arthroplasty (TJA) suggests a potential opportunity to reduce preventable discharge delays. Previous studies investigated the impact of social determinants of health (SDoH) on orthopaedic conditions and outcomes using deprivation indices with inconsistent findings. The aim of the study is to compare the association of three publicly available national indices of social deprivation with prolonged LOS in revision TJA patients. MATERIALS AND METHODS: 1,047 consecutive patients who underwent a revision TJA were included in this retrospective study. Patient demographics, comorbidities, and behavioral characteristics were extracted. Area deprivation index (ADI), social deprivation index (SDI), and social vulnerability index (SVI) were recorded for each patient, following which univariate and multivariate logistic regression analyses were performed to determine the relationship between deprivation measures and prolonged LOS (greater than five days postoperatively). RESULTS: 193 patients had a prolonged LOS following surgery. Categorical ADI was significantly associated with prolonged LOS following surgery (OR = 2.14; 95% CI = 1.30-3.54; p = 0.003). No association with LOS was found using SDI and SVI. When accounting for other covariates, only ASA scores (ORrange=3.43-3.45; p < 0.001) and age (ORrange=1.00-1.03; prange=0.025-0.049) were independently associated with prolonged LOS. CONCLUSION: The varying relationship observed between the length of stay and socioeconomic markers in this study indicates that the selection of a deprivation index could significantly impact the outcomes when investigating the association between socioeconomic deprivation and clinical outcomes. These results suggest that ADI is a potential metric of social determinants of health that is applicable both clinically and in future policies related to hospital stays including bundled payment plan following revision TJA.

7.
J Imaging Inform Med ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38954293

RESUMEN

This study aims to evaluate an AI model designed to automatically classify skull fractures and visualize segmentation on emergent CT scans. The model's goal is to boost diagnostic accuracy, alleviate radiologists' workload, and hasten diagnosis, thereby enhancing patient outcomes. Unique to this research, both pediatric and post-operative patients were not excluded, and diagnostic durations were analyzed. Our testing dataset for the observer studies involved 671 patients, with a mean age of 58.88 years and fairly balanced gender representation. Model 1 of our AI algorithm, trained with 1499 fracture-positive cases, showed a sensitivity of 0.94 and specificity of 0.87, with a DICE score of 0.65. Implementing post-processing rules (specifically Rule B) improved the model's performance, resulting in a sensitivity of 0.94, specificity of 0.99, and a DICE score of 0.63. AI-assisted diagnosis resulted in significantly enhanced performance for all participants, with sensitivity almost doubling for junior radiology residents and other specialists. Additionally, diagnostic durations were significantly reduced (p < 0.01) with AI assistance across all participant categories. Our skull fracture detection model, employing a segmentation approach, demonstrated high performance, enhancing diagnostic accuracy and efficiency for radiologists and clinical physicians. This underlines the potential of AI integration in medical imaging analysis to improve patient care.

8.
BMC Biol ; 22(1): 146, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956599

RESUMEN

BACKGROUND: Metabolic associated fatty liver disease (MAFLD), a prevalent liver disorder affecting one-third of the global population, encompasses a spectrum ranging from fatty liver to severe hepatic steatosis. Both genetic and lifestyle factors, particularly diet and nutrition, contribute to its etiology. Folate deficiency, a frequently encountered type of malnutrition, has been associated with the pathogenesis of MAFLD and shown to impact lipid deposition. However, the underlying mechanisms of this relationship remain incompletely understood. We investigated the impact of disturbed folate-mediated one-carbon metabolism (OCM) on hepatic lipid metabolism both in vitro using human hepatoma cells and in vivo using transgenic fluorescent zebrafish displaying extent-, stage-, and duration-controllable folate deficiency upon induction. RESULTS: Disturbed folate-mediated one-carbon metabolism, either by inducing folate deficiency or adding anti-folate drug, compromises autophagy and causes lipid accumulation in liver cells. Disturbed folate status down-regulates cathepsin L, a key enzyme involved in autophagy, through inhibiting mTOR signaling. Interfered mitochondrial biology, including mitochondria relocation and increased fusion-fission dynamics, also occurs in folate-deficient hepatocytes. Folate supplementation effectively mitigated the impaired autophagy and lipid accumulation caused by the inhibition of cathepsin L activity, even when the inhibition was not directly related to folate deficiency. CONCLUSIONS: Disruption of folate-mediated OCM diminishes cathepsin L expression and impedes autophagy via mTOR signaling, leading to lipid accumulation within hepatocytes. These findings underscore the crucial role of folate in modulating autophagic processes and regulating lipid metabolism in the liver.


Asunto(s)
Autofagia , Ácido Fólico , Hepatocitos , Homeostasis , Metabolismo de los Lípidos , Pez Cebra , Autofagia/fisiología , Ácido Fólico/metabolismo , Humanos , Hepatocitos/metabolismo , Animales , Deficiencia de Ácido Fólico/metabolismo
9.
J Prosthodont ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023016

RESUMEN

PURPOSE: The present study evaluated the effects of the root portion design, segment (middle vs. apical), and part (die vs. cast) on the trueness of three-dimensional (3D)-printed removable die-cast complex. MATERIAL AND METHODS: The trueness of apical and middle segments of the root portion of 45 3D-printed removable dies and casts with three different root portion designs (n = 15) was assessed using a metrology-grade computer program. The three removable dies and cast designs (root form [RF], conical [CON], and cylindric [CYL]) were created using professional computer-aided manufacturing computer programs (DentalCAD 3.1 Rijeka, and InLab CAD 22.0), and manufactured using stereolithographic 3D printer (Form3; FormLabs, Somerville, MA). Subsequently, the 3D-printed removable dies and casts were scanned by a single operator with an intraoral scanner (PrimeScan; Dentsply Sirona, Charlotte, NC), and their respective standard tessellation language files were aligned and compared to master reference files in a metrology-grade computer program (Geomagic Control X; 3D systems, Rock Hill, NC). The root mean square (RMS) values of the middle and apical segments for each removable die and cast were calculated and analyzed using a mixed model including a repeated measure 3-way analysis of variance (ANOVA) and post-hoc stepdown Bonferroni-corrected pairwise comparisons (α = 0.05). RESULTS: A statistically significant 3-way interaction between factors was detected, suggesting that the part (removable die or alveolar cast) and their design affected the RMS values of their apical and middle root portion segment. (p = 0.045). The post-hoc analysis identified significant differences between RMS values of the apical segments of the CON and CYL removable dies (p = 0.005). Significant differences were observed between the middle and apical segments of the CON (p < 0.001) and RF removable die designs (p = 0.004). No statistically significant differences were noticed between the RMS of the different alveolar cast designs (p > 0.05). Significant differences were detected between the apical and middle segments of the same alveolar cast design (p < 0.05). CONCLUSIONS: For the manufacturing trinomial and 3D printing strategy used in the present study, the interaction of the part, design, and segment affected the trueness of removable dies and alveolar casts. The trueness was higher on the middle segment on removable dies and alveolar casts in all designs used, except for CYL removable dies, where the trueness difference between segments was small. Higher trueness values may be achieved with designs with simple apical segment geometries.

11.
Research (Wash D C) ; 7: 0398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015205

RESUMEN

Facing the challenge of achieving the goal of carbon neutrality, China is decoupling the currently close dependence of its economy on coal use. The energy supply and demand decarbonization has substantial influence on the resilience of the coal supply. However, a general understanding of the precise impact of energy decarbonization on the resilience of the coal energy supply is still lacking. Here, from the perspective of network science, we propose a theoretical framework to explore the resilience of the coal market of China. We show that the processes of increasing the connectivity and the competition between the coal enterprises, which are widely believed to improve the resilience of the coal market, can undermine the sustainability of the coal supply. Moreover, our results reveal that the policy of closing small-sized coal mines may not only reduce the safety accidents in the coal production but also improve the resilience of the coal market network. Using our model, we also suggest a few practical policies for minimizing the systemic risk of the coal energy supply.

12.
Cancer Imaging ; 24(1): 91, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992679

RESUMEN

BACKGROUND: This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm. METHODS: Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures. RESULTS: Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09-1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96-1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10-1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size < 1 cm. CONCLUSIONS: In patients with stage I NSCLC and tumor size < 1 cm, thermal ablation has similar OS and CSS with wedge resection.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Estados Unidos/epidemiología , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Neumonectomía/métodos , Neumonectomía/mortalidad , Tasa de Supervivencia
13.
Am J Cancer Res ; 14(6): 3153-3170, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005663

RESUMEN

Non-small cell lung cancer (NSCLC) is one of the prevalent malignancies. Cisplatin (CDDP) is a conventional chemotherapeutic agent against NSCLC. However, inherent and acquired chemoresistance limited the effectiveness of cisplatin in treatment of NSCLC. This study aimed to investigate the roles and underlying mechanisms of lncRNA-FEZF1-AS1 in mediating cisplatin sensitivity in NSCLC. We found that FEZF1-AS1 levels were significantly higher in lung cancer patients and cell lines. Blocking FEZF1-AS1 sensitized lung cancer cells to cisplatin. Additionally, both glutamine metabolism and FEZF1-AS1 were significantly elevated in cisplatin resistant NSCLC cell lines, A549/CDDP R and SK-MES-1 CDDP/R. Analysis using bioinformatics, RNA pull-down assay and luciferase assay demonstrated that FEZF1-AS1 sponged miR-32-5p, which acted as a tumor suppressor in NSCLC. Glutaminase (GLS), a key enzyme in the glutamine metabolism, was predicted and validated as the direct target of miR-32-5p in NSCLC cells. Inhibiting glutamine metabolism or reducing glutamine supply effectively resensitized cisplatin-resistant cells. Furthermore, restoring miR-32-5p in FEZF1-AS1-overexpressing cisplatin resistant cells successfully overcame FEZF1-AS1-mediated cisplatin resistance by targeting GLS. These findings were further supported by in vivo xenograft mice experiments. This study uncovered the roles and molecular mechanisms of lncRNA FEZF1-AS1 in mediating cisplatin resistance in NSCLC, specifically through modulating the miR-32-5p-GLS axis, providing support for the development of new therapeutic approaches against chemoresistant lung cancer.

14.
Heliyon ; 10(12): e33181, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39005927

RESUMEN

Trichomonas tenax, an oral commensal parasite commonly found in the human mouth, is associated with periodontitis and poor oral hygiene. However, it has also been identified in the bronchoalveolar lavage fluid (BALF) of individuals with lung diseases. Notably, significant quantities of T. tenax have been isolated following bronchoscopy in cases of empyema and acute respiratory distress syndrome (ARDS). Furthermore, research has demonstrated its ability to induce inflammation in pulmonary epithelial cells. To comprehend the potential role of T. tenax in pneumonia, it is crucial to elucidate the relationship between the parasite and the disease. We investigated the clinical factors associated with T. tenax infection in patients with pneumonia. Employing nested polymerase chain reactions, we amplified nucleic acids from BALF and analyzed the relationships between T. tenax and various clinical factors. Our data revealed a significant association between T. tenax and bacterial infections, high pneumonia severity index (PSI) scores, nasogastric tube feeding, and pulmonary complications. Logistic regression analyses also showed strong associations between T. tenax and these clinical factors in pneumonia patients. These findings suggest that T. tenax infection in pneumonia is accompanied by bacterial infection and severe clinical manifestations.

15.
Ecotoxicol Environ Saf ; 282: 116724, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003870

RESUMEN

Benzovindiflupyr is a succinate dehydrogenase inhibitor fungicide that targets mitochondrial function for disease control. In this study, we investigated the adsorption-desorption and leaching behavior of benzovindiflupyr in eight soil types using the batch equilibrium method and the soil column leaching method. A Freundlich model (r2 > 0.9959) was used to better characterize the adsorption-desorption process in eight soil types, with adsorption coefficients (KF-ads) ranging from 2.303 to 17.886. KF-ads was significantly and positively correlated (p < 0.05) with the organic carbon content. High temperatures and increased initial pH of aqueous solutions led to a decrease in benzovindiflupyr adsorption in the soil. The adsorption was also influenced by factors such as ionic strength, humic acid, surfactant type, microplastic type, and particle size and concentration. Moreover, benzovindiflupyr exhibited low leachability in all four soils selected, but different leaching solutions affected the risk of benzovindiflupyr migration to groundwater. Overall, this study provides insights into the adsorption characteristics of benzovindiflupyr in different soils and provides key information for environmental risk assessment.

16.
Int J Hyperthermia ; 41(1): 2378865, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39004424

RESUMEN

OBJECTIVES: This study evaluated the long-term efficacy and safety of radiofrequency ablation (RFA) for intrathoracic goiter (ITG) over a follow-up period exceeding six months. METHODS: From 2017 to 2022, 22 patients (6 males, 16 females) with 24 ITGs treated with RFA at a single medical center were evaluated. All patients underwent ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI) before RFA. Follow-up CT/MRI was performed six months after the initial RFA and then every 6-12 months. The primary outcomes measured were the degree of extension, goiter volume, volume reduction rate (VRR), tracheal deviation, and tracheal lumen. Additionally, we assessed the outcomes of single-session RFA (n = 16) vs. multiple sessions (n = 8) on goiters and explored the correlation between ITG volume measurements obtained using ultrasonography and CT/MRI. RESULTS: The median follow-up period was 12 months (interquartile range: 6-36.8 months). At the last follow-up, the nodule volume measured by CT/MRI had significantly decreased (76.2 vs. 24.6 mL; p < 0.05), with a VRR of 64.6%. Patients who underwent multiple RFA sessions showed a significantly higher VRR than the single-session patients (63.8 vs. 80.1%, p < 0.05). The intraclass correlation between goiter volumes measured using US and CT/MRI was moderate. CONCLUSION: This study affirms the long-term efficacy and safety of RFA for ITG, providing an alternative treatment for nonsurgical candidates. Multiple RFA sessions may be beneficial for achieving better volume reduction. Sole reliance on ultrasonography is inadequate; therefore, integrating CT/MRI is essential for accurate pre-RFA and follow-up assessments.


Intrathoracic goiters significantly impact both cosmetic appearance and induce numerous compressive symptoms.Radiofrequency ablation brought notable volume reduction and persistent, effective alleviation of compressive symptoms.Radiofrequency ablation presents a promising therapeutic modality with long-term benefits for patients with intrathoracic goiter.


Asunto(s)
Imagen por Resonancia Magnética , Ablación por Radiofrecuencia , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Ablación por Radiofrecuencia/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Ultrasonografía/métodos , Adulto , Resultado del Tratamiento , Bocio Subesternal/diagnóstico por imagen , Bocio Subesternal/cirugía
17.
Mol Cancer ; 23(1): 141, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982480

RESUMEN

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.


Asunto(s)
Progresión de la Enfermedad , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Proteínas Proto-Oncogénicas c-myc , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Animales , Ratones , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Línea Celular Tumoral , Fosfofructoquinasa-1 Tipo C/metabolismo , Fosfofructoquinasa-1 Tipo C/genética , Proliferación Celular , Pronóstico , Femenino , Masculino , Ensayos Antitumor por Modelo de Xenoinjerto , Biomarcadores de Tumor/metabolismo
18.
Cancer Cell Int ; 24(1): 239, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982494

RESUMEN

BACKGROUND: In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. MAIN BODY: Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. CONCLUSION: ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach.

19.
Inorg Chem ; 63(28): 13031-13038, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38957956

RESUMEN

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

20.
Cell Mol Life Sci ; 81(1): 283, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963422

RESUMEN

Protein SUMOylation is a prevalent stress-response posttranslational modification crucial for maintaining cellular homeostasis. Herein, we report that protein SUMOylation modulates cellular signaling mediated by cAMP, an ancient and universal stress-response second messenger. We identify K561 as a primary SUMOylation site in exchange protein directly activated by cAMP (EPAC1) via site-specific mapping of SUMOylation using mass spectrometry. Sequence and site-directed mutagenesis analyses reveal that a functional SUMO-interacting motif in EPAC1 is required for the binding of SUMO-conjugating enzyme UBC9, formation of EPAC1 nuclear condensate, and EPAC1 cellular SUMOylation. Heat shock-induced SUMO modification of EPAC1 promotes Rap1/2 activation in a cAMP-independent manner. Structural modeling and molecular dynamics simulation studies demonstrate that SUMO substituent on K561 of EPAC1 promotes Rap1 interaction by increasing the buried surface area between the SUMOylated receptor and its effector. Our studies identify a functional SUMOylation site in EPAC1 and unveil a novel mechanism in which SUMOylation of EPAC1 leads to its autonomous activation. The findings of SUMOylation-mediated activation of EPAC1 not only provide new insights into our understanding of cellular regulation of EPAC1 but also will open up a new field of experimentation concerning the cross-talk between cAMP/EPAC1 signaling and protein SUMOylation, two major cellular stress response pathways, during cellular homeostasis.


Asunto(s)
AMP Cíclico , Factores de Intercambio de Guanina Nucleótido , Sumoilación , Enzimas Ubiquitina-Conjugadoras , Proteínas de Unión al GTP rap1 , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/química , Humanos , AMP Cíclico/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Proteínas de Unión al GTP rap1/metabolismo , Proteínas de Unión al GTP rap1/genética , Células HEK293 , Simulación de Dinámica Molecular , Complejo Shelterina/metabolismo , Transducción de Señal , Proteínas de Unión a Telómeros/metabolismo , Proteínas de Unión al GTP rap/metabolismo , Proteínas de Unión al GTP rap/genética , Respuesta al Choque Térmico , Secuencia de Aminoácidos , Unión Proteica
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