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1.
IEEE Trans Med Imaging ; PP2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39475746

RESUMEN

Segmentation is a critical step in analyzing the developing human fetal brain. There have been vast improvements in automatic segmentation methods in the past several years, and the Fetal Brain Tissue Annotation (FeTA) Challenge 2021 helped to establish an excellent standard of fetal brain segmentation. However, FeTA 2021 was a single center study, limiting real-world clinical applicability and acceptance. The multi-center FeTA Challenge 2022 focused on advancing the generalizability of fetal brain segmentation algorithms for magnetic resonance imaging (MRI). In FeTA 2022, the training dataset contained images and corresponding manually annotated multi-class labels from two imaging centers, and the testing data contained images from these two centers as well as two additional unseen centers. The multi-center data included different MR scanners, imaging parameters, and fetal brain super-resolution algorithms applied. 16 teams participated and 17 algorithms were evaluated. Here, the challenge results are presented, focusing on the generalizability of the submissions. Both in- and out-of-domain, the white matter and ventricles were segmented with the highest accuracy (Top Dice scores: 0.89, 0.87 respectively), while the most challenging structure remains the grey matter (Top Dice score: 0.75) due to anatomical complexity. The top 5 average Dices scores ranged from 0.81-0.82, the top 5 average 95th percentile Hausdorff distance values ranged from 2.3-2.5mm, and the top 5 volumetric similarity scores ranged from 0.90-0.92. The FeTA Challenge 2022 was able to successfully evaluate and advance generalizability of multi-class fetal brain tissue segmentation algorithms for MRI and it continues to benchmark new algorithms.

2.
Nucleic Acids Res ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39420637

RESUMEN

Investigating mutations, including single nucleotide variations (SNVs), gene fusions, alternative splicing and copy number variations (CNVs), is fundamental to cancer study. Recent computational methods and biological research have demonstrated the reliability and biological significance of detecting mutations from single-cell transcriptomic data. However, there is a lack of a single-cell-level database containing comprehensive mutation information in all types of cancer. Establishing a single-cell mutation landscape from the huge emerging single-cell transcriptomic data can provide a critical resource for elucidating the mechanisms of tumorigenesis and evolution. Here, we developed scTML (http://sctml.xglab.tech/), the first database offering a pan-cancer single-cell landscape of multiple mutation types. It includes SNVs, insertions/deletions, gene fusions, alternative splicing and CNVs, along with gene expression, cell states and other phenotype information. The data are from 74 datasets with 2 582 633 cells, including 35 full-length (Smart-seq2) transcriptomic single-cell datasets (all publicly available data with raw sequencing files), 23 datasets from 10X technology and 16 spatial transcriptomic datasets. scTML enables users to interactively explore multiple mutation landscapes across tumors or cell types, analyze single-cell-level mutation-phenotype associations and detect cell subclusters of interest. scTML is an important resource that will significantly advance deciphering intra-tumor and inter-tumor heterogeneity, and how mutations shape cell phenotypes.

3.
Micromachines (Basel) ; 15(8)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39203595

RESUMEN

The combination of multiplex polymerase chain reaction (mPCR) and microfluidic technologies demonstrates great significance in biomedical applications. However, current microfluidics-based molecular diagnostics face challenges in multi-target detection due to their limited fluorescence channels, complicated fabrication process, and high cost. In this research, we proposed a cost-effective sandblasting method for manufacturing silicon microchips and a chip-based microdevice for field mPCR detection. The atomic force microscopy (AFM) images showed a rough surface of the sandblasted microchips, leading to poor biocompatibility. To relieve the inhibitory effect, we dip-coated a layer of bovine serum albumin (BSA) on the irregular substrate. The optimized coating condition was determined by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) (65 °C for 60 min). After sufficient coating, we performed on-chip PCR tests with 500 copies/mL Coronavirus Disease 2019 (COVID-19) standard sample within 20 min, and the sandblasted microchip displayed a higher amplification rate compared to dry etching chips. Finally, we achieved a 50 min mPCR for screening five resistance genes of the endophthalmitis pathogens on our microdevices, with strong specificity and reliability. Thus, this sandblasted microchip-based platform not only provides a rapid, accessible, and effective solution for multiplex molecular detection but also enables large-scale microfabrication in a low-cost and convenient way.

4.
BMC Psychol ; 12(1): 443, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152489

RESUMEN

Neuroticism appears to be a factor that triggers social aggression, but the relationship between neuroticism and social aggression and its underlying mechanisms is unclear. Questionnaire data from 942 college students ranging in age from 17 to 24 (Mage = 20.33, SD = 1.03) were analysed to assess whether depression symptoms mediated the relationship between neuroticism and social aggression, and to test a moderating effect of perceived social support. Results showed that neuroticism positively predicted social aggression and this association was mediated by depression symptoms. Moderation was found for the association between neuroticism and depression symptoms, as well as between neuroticism and social aggression, and that neuroticism had a stronger predictive effect on depression symptoms and social aggression under low compared to high perceived social support. These findings may inform prevention and intervention efforts to reduce social aggression.


Asunto(s)
Agresión , Depresión , Neuroticismo , Humanos , Agresión/psicología , Masculino , Femenino , Adulto Joven , Depresión/psicología , Adolescente , Apoyo Social , Encuestas y Cuestionarios , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Adulto , Análisis de Mediación , Conducta Social
5.
Nat Nanotechnol ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164411

RESUMEN

Microstrain and the associated surface-to-bulk propagation of structural defects are known to be major roadblocks to developing high-energy and long-life batteries. However, the origin and effects of microstrain during the synthesis of battery materials remain largely unknown. Here we perform microstrain screening during real-time and realistic synthesis of sodium layered oxide cathodes. Evidence gathered from multiscale in situ synchrotron X-ray diffraction and microscopy characterization collectively reveals that the spatial distribution of transition metals within individual precursor particles strongly governs the nanoscale phase transformation, local charge heterogeneity and accumulation of microstrain during synthesis. This unexpected dominance of transition metals results in a counterintuitive outward propagation of defect nucleation and growth. These insights direct a more rational synthesis route to reduce the microstrain and crystallographic defects within the bulk lattice, leading to significantly improved structural stability. The present work on microstrain screening represents a critical step towards synthesis-by-design of defect-less battery materials.

6.
Mol Cancer ; 23(1): 173, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175001

RESUMEN

BACKGROUND: Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. METHODS: In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5' end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. RESULTS: This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965-0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. CONCLUSION: Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Metilación de ADN , Detección Precoz del Cáncer , Multiómica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Ácidos Nucleicos Libres de Células/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/sangre , Variaciones en el Número de Copia de ADN , Detección Precoz del Cáncer/métodos , Genómica/métodos , Biopsia Líquida/métodos , Multiómica/métodos , Mutación
7.
EBioMedicine ; 105: 105212, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38954976

RESUMEN

BACKGROUND: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC. METHODS: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system. FINDINGS: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression. INTERPRETATION: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC. FUNDING: The funding details can be found in the Acknowledgements section.


Asunto(s)
Proteína p300 Asociada a E1A , Péptidos , Neoplasias de la Próstata , Proteolisis , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Humanos , Proteolisis/efectos de los fármacos , Animales , Ratones , Línea Celular Tumoral , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteína p300 Asociada a E1A/metabolismo , Péptidos/farmacología , Péptidos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Modelos Animales de Enfermedad , Receptores Androgénicos/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Descubrimiento de Drogas
8.
Front Oncol ; 14: 1442627, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070145

RESUMEN

Background and purpose: Current studies have substantiated the sparing effect of ultra-high dose rate irradiation (FLASH) in various organs including the brain, lungs, and intestines. Whether this sparing effect extends to esophageal tissue remains unexplored. This study aims to compare the different responses of esophageal tissue in histological and protein expression levels following conventional dose rate irradiation (CONV) and FLASH irradiation to ascertain the presence of a sparing effect. Methods and materials: C57 female mice were randomly divided into three groups: control, CONV, and FLASH groups. The chest region of the mice in the radiation groups was exposed to a prescribed dose of 20 Gy using a modified electron linear accelerator. The CONV group received an average dose rate of 0.1 Gy/s, while the FLASH group received an average dose rate of 125 Gy/s. On the 10th day after irradiation, the mice were euthanized and their esophagi were collected for histopathological analysis. Subsequently, label-free proteomic quantification analysis was performed on esophageal tissue. The validation process involved analyzing transmission electron microscopy images and utilizing the parallel reaction monitoring method. Results: Histopathology results indicated a significantly lower extent of esophageal tissue damage in the FLASH group compared to the CONV group (p < 0.05). Label-free quantitative proteomic analysis revealed that the sparing effect observed in the FLASH group may be attributed to a reduction in radiation-induced protein damage associated with mitochondrial functions, including proteins involved in the tricarboxylic acid cycle and oxidative phosphorylation, as well as a decrease in acute inflammatory responses. Conclusions: Compared with CONV irradiation, a sparing effect on esophageal tissue can be observed after FLASH irradiation. This sparing effect is associated with alleviated mitochondria damage and acute inflammation.

9.
JTO Clin Res Rep ; 5(6): 100678, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38846810

RESUMEN

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

10.
Iran J Public Health ; 53(3): 634-643, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38919311

RESUMEN

Background: We aimed to explore the epidemiological trends and characteristics of undernutrition among children and adolescents aged 7~18 years in Macao from 2005 to 2020 to provide insights into the improvement of nutritional status among the youth in Macao, China. Methods: Based on the data collected from the Citizen Physical Fitness surveillance sessions in Macao in 2005, 2010, 2015, and 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was calculated. Result: In 2020, the prevalence of undernutrition among children and adolescents aged 7~18 years in Macao was 12.11%. Among them, the rates of stunting, moderate or severe wasting, and mild wasting were 0.63%, 5.25%, and 6.23%, respectively. The prevalence of undernutrition among boys (13.81%) was higher than that among girls (10.06%). Mild wasting was the main form of undernutrition among students. From 2005 to 2020, the prevalence of malnutrition showed a decreasing trend (P<0.05), but there was a rebound in 2020 from 2015, mainly because it may be caused by the COVID-19 pandemic in 2020. The prevalence of undernutrition among children and adolescents in Macao was lower than that in Mainland China (P<0.01). Conclusion: The detection rates of undernutrition showed a decreasing trend from 2005 to 2020. In the post-pandemic era, Macao should undertake more effective measures in areas such as promoting balanced nutritional intake, increasing physical activity levels, enhancing school physical education, and incorporating mental health education. These efforts are essential for further reducing the prevalence of undernutrition among children and adolescents.

11.
J Med Chem ; 67(12): 10336-10349, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38836467

RESUMEN

While large-scale artificial intelligence (AI) models for protein structure prediction and design are advancing rapidly, the translation of deep learning models for practical macromolecular drug development remains limited. This investigation aims to bridge this gap by combining cutting-edge methodologies to create a novel peptide-based PROTAC drug development paradigm. Using ProteinMPNN and RFdiffusion, we identified binding peptides for androgen receptor (AR) and Von Hippel-Lindau (VHL), followed by computational modeling with Alphafold2-multimer and ZDOCK to predict spatial interrelationships. Experimental validation confirmed the designed peptide's binding ability to AR and VHL. Transdermal microneedle patching technology was seamlessly integrated for the peptide PROTAC drug delivery in androgenic alopecia treatment. In summary, our approach provides a generic method for generating peptide PROTACs and offers a practical application for designing potential therapeutic drugs for androgenetic alopecia. This showcases the potential of interdisciplinary approaches in advancing drug development and personalized medicine.


Asunto(s)
Alopecia , Diseño de Fármacos , Péptidos , Receptores Androgénicos , Alopecia/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Receptores Androgénicos/química , Humanos , Péptidos/química , Péptidos/farmacología , Péptidos/uso terapéutico , Animales , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/química , Masculino
12.
Drug Resist Updat ; 76: 101096, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38924996

RESUMEN

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.


Asunto(s)
Cisplatino , Resistencia a Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción de Tipo Kruppel , Molécula L1 de Adhesión de Célula Nerviosa , Humanos , Cisplatino/farmacología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/genética , Línea Celular Tumoral , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Metástasis de la Neoplasia , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Proteínas de Motivos Tripartitos , Proteínas de Unión al ADN , Proteínas Nucleares
13.
Adv Mater ; 36(33): e2310659, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38871360

RESUMEN

Layered iron/manganese-based oxides are a class of promising cathode materials for sustainable batteries due to their high energy densities and earth abundance. However, the stabilization of cationic and anionic redox reactions in these cathodes during cycling at high voltage remain elusive. Here, an electrochemically/thermally stable P2-Na0.67Fe0.3Mn0.5Mg0.1Ti0.1O2 cathode material with zero critical elements is designed for sodium-ion batteries (NIBs) to realize a highly reversible capacity of ≈210 mAh g-1 at 20 mA g-1 and good cycling stability with a capacity retention of 74% after 300 cycles at 200 mA g-1, even when operated with a high charge cut-off voltage of 4.5 V versus sodium metal. Combining a suite of cutting-edge characterizations and computational modeling, it is shown that Mg/Ti co-doping leads to stabilized surface/bulk structure at high voltage and high temperature, and more importantly, enhances cationic/anionic redox reaction reversibility over extended cycles with the suppression of other undesired oxygen activities. This work fundamentally deepens the failure mechanism of Fe/Mn-based layered cathodes and highlights the importance of dopant engineering to achieve high-energy and earth-abundant cathode material for sustainable and long-lasting NIBs.

14.
Transl Lung Cancer Res ; 13(4): 821-838, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38736484

RESUMEN

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and lymph node dissection (LND) is a significant surgical procedure employed in its management. Although some studies suggest benefits of LND, the extent of its impact on survival, the optimal range of lymph nodes to be examined, and the specific patient groups that benefit most remain areas of active debate and investigation. Methods: A population-based analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with NSCLC between 2004 and 2017, undergoing primary tumor resection, were included. Descriptive, univariate, and multivariate analyses assessed the effect of LND on survival, and a restricted cubic spline method determined the optimal range for lymph node examination. Results: This study of 37,323 NSCLC patients delved into the impact of LND on lung cancer-specific survival. Key findings revealed a median survival of 19.58 months, with 85% mortality. Baseline characteristics included a majority of White patients (81%), distant stage diagnoses (63%), and 64% with Grade IV tumors. LND emerged as a crucial predictor, influencing survival across age, gender, race, and tumor characteristics. Univariate analysis highlighted its significance, with higher T, N, and M categories, advanced stage, and poorer grade associating with elevated hazard ratios. Multivariate Cox proportional hazards (PH) analysis reinforced LND's impact, showcasing lower hazard ratios post-removal. Hazard ratios for biopsy/aspiration and removal of regional lymph nodes were 0.85 [95% confidence interval (CI): 0.81-0.89; P<0.001] and 0.43 (95% CI: 0.39-0.46; P<0.001), underscoring the protective effect. Visualizations and a U-shaped curve analysis identified an optimal range (24-32 nodes) for examination, emphasizing the nuanced benefits across NSCLC stages. Conclusions: The study findings suggest that LND plays a critical role in improving cancer-specific survival in NSCLC patients, particularly when tailored to the early stages of the disease. The optimal range of lymph nodes examined, between 24 and 32, offers crucial insights for personalized NSCLC treatment strategies and may enhance overall survival. These results underscore the need for refined surgical guidelines that incorporate the extent of LND, supporting the utility of a more personalized approach in NSCLC management.

15.
Cancer Rep (Hoboken) ; 7(5): e2003, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38703000

RESUMEN

BACKGROUND: Mid-rectal cancer treatment traditionally involves conventional laparoscopic-assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. AIMS: To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long-term prognosis between NOSES and CLAR groups. MATERIALS & METHODS: A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. RESULTS: The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. CONCLUSION: While long-term outcomes (overall survival, disease-free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid-rectal cancer treatment, while maintaining similar long-term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long-term results.


Asunto(s)
Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Neoplasias del Recto , Humanos , Femenino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Masculino , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Persona de Mediana Edad , Anciano , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Calidad de Vida , Puntaje de Propensión
18.
Oncogene ; 43(26): 2025-2037, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38744954

RESUMEN

Lung adenocarcinoma (LUAD) is one of the most prevalent types of cancer. Ubiquitination is crucial in modulating cell proliferation and aerobic glycolysis in cancer. The frequency of TP53 mutations in LUAD is approximately 50%. Currently, therapeutic targets for wild-type (WT) p53-expressing LUAD are limited. In the present study, we systemically explored the expression of ubiquitin-specific protease genes using public datasets. Then, we focused on ubiquitin-specific protease 54 (USP54), and explored its prognostic significance in LUAD patients using public datasets, analyses, and an independent cohort from our center. We found that the expression of USP54 was lower in LUAD tissues compared with that in the paracancerous tissues. Low USP54 expression levels were linked to a malignant phenotype and worse survival in patients with LUAD. The results of functional experiments revealed that up-regulation of USP54 suppressed LUAD cell proliferation in vivo and in vitro. USP54 directly interacted with p53 protein and the levels of ubiquitinated p53 were inversely related to USP54 levels, consistent with a role of USP54 in deubiquitinating p53 in p53-WT LUAD cells. Moreover, up-regulation of the USP54 expression inhibited aerobic glycolysis in LUAD cells. Importantly, we confirmed that USP54 inhibited aerobic glycolysis and the growth of tumor cells by a p53-mediated decrease in glucose transporter 1 (GLUT1) expression in p53-WT LUAD cells. Altogether, we determined a novel mechanism of survival in the p53-WT LUAD cells to endure the malnourished tumor microenvironment and provided insights into the role of USP54 in the adaptation of p53-WT LUAD cells to metabolic stress.


Asunto(s)
Adenocarcinoma del Pulmón , Transportador de Glucosa de Tipo 1 , Glucólisis , Neoplasias Pulmonares , Proteína p53 Supresora de Tumor , Animales , Femenino , Humanos , Masculino , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Glucólisis/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones Desnudos , Pronóstico , Proteolisis , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/genética , Ubiquitinación
19.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38612682

RESUMEN

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.


Asunto(s)
Neoplasias , Escualeno-Monooxigenasa , Humanos , Muerte Celular , Colesterol , Ácido Mevalónico , Neoplasias/genética , Escualeno-Monooxigenasa/genética
20.
Small ; 20(31): e2312288, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38431966

RESUMEN

The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3O4-FeTe nanoparticles. The Fe3O4-FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3O4-FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.

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