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The expression "lost at sea" means to be confused or perplexed. By extension, lost at SCLC references the current confusion about how to circumvent the chemoresistance, particularly platinum resistance, which so plagues the treatment of extensive-stage small cell lung cancer (ES-SCLC) that in 2012 the US National Cancer Institute (NCI) designated it a "recalcitrant cancer." Over a decade later, despite the approval of immune checkpoint inhibitors and the conditional approval of lurbinectedin, the prognosis for ES-SCLC, and especially platinum-resistant ES-SCLC, has scarcely improved. The focus of this review, which briefly summarizes current treatment options for ES-SCLC, is on five clinical-stage therapies with the potential to successfully reverse the platinum resistance that is perhaps the biggest obstacle to better clinical outcomes.
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This study aimed to evaluate the relationship between the precise three-dimensional location of the third molar (M3) and mandibular angle fracture (MAF) patterns and to assess the effect of the volume ratio occupied by M3 in the mandibular angle on fracture patterns. The location of M3 was assessed in 218 patients with MAF using computed tomography reconstruction. The bone volume of the mandibular angle and the bone volume occupied by M3 were measured to calculate the volume ratio of M3 to the mandibular angle (M3/MA). MAF patterns were categorized into simple fracture (Type I), displaced fracture (Type II), and comminuted fracture (Type III) based on fracture severity. The results showed that the location of M3 significantly influenced MAF patterns (vertical position: P = .001; horizontal position: P = .002; angulation: P = .027, respectively) and the volume ratio of M3/MA was significantly higher for Type III fracture than Types I and II (P < .001). Regression analysis showed that the horizontal position and angulation of M3 and the volume ratio of M3/MA were the main predictors for comminuted MAF. A larger volume ratio (odds ratio [OR], 1.201; 95% confidence interval [CI], 1.037-1.391; P < .014), Class III position (OR, 7.978; 95% CI, 1.275-49.910; P < .026), and horizontal angulation (OR, 7.212; 95% CI, 1.028-50.581; P < .047) of the M3 were more prone to comminuted MAF than simple fracture. Our findings indicate that the location of M3 significantly affects MAF patterns, and that M3 may weaken the mandibular angle by occupying more bone space, thereby increasing the risk of a comminuted fracture.
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Bone metastasis is a lethal consequence of breast cancer. Here we used single-cell transcriptomics to investigate the molecular mechanisms underlying bone metastasis colonization-the rate-limiting step in the metastatic cascade. We identified that lymphotoxin-ß (LTß) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTß promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTß activates osteoblasts through nuclear factor-κB2 signalling to secrete CCL2/5, which facilitates tumour cell adhesion to osteoblasts and accelerates osteoclastogenesis, leading to bone metastasis progression. Blocking LTß signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTß expression in bone metastases than in primary tumours. Our findings highlight LTß as a bone niche-induced factor that promotes tumour cell colonization and osteolytic outgrowth and underscore its potential as a therapeutic target for patients with bone metastatic disease.
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A novel and simple ratiometric fluorescent aptasensor was developed for the sensitive detection of aflatoxin B1 (AFB1). A hairpin DNA (h-DNA) was independently synthesized as the basic skeleton, and the bidirectional hybridization of h-DNA can increase the load of aptamer and signal probes, thereby realizing signal amplification. The high-efficiency fluorescence resonance energy transfer interaction between gold-palladium nanoparticles (Au-Pd NPs) and the self-synthesized fluorescent probe carbon dots (CDs) was utilized. Moreover, the label-free probe SYBR Green I (SG I) dye was introduced to form a double-signal probe with CDs, and a ratiometric sensor with FCDs/FSG I as a response signal was constructed. The ratio strategy can eliminate the fluctuation of external factors, thus improving the accuracy and reliability of the sensor. The quenching effect of Au-Pd NPs on CDs was 1.4 times that of AuNPs and 3.4 times that of Pd NPs, respectively. In the range 1-100 ng/mL, FCDs/FSG I showed a good linear relationship with the logarithm of the concentration of AFB1, and the limit of detection was as low as 0.07 ng/mL. The sensor was used to detect AFB1 in spiked peanuts and wine samples, and the recovery was between 91 and 115%, indicating that the sensor has high application potential in real sample analysis.
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Aflatoxina B1 , Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Carbono , Corantes Fluorescentes , Ouro , Limite de Detecção , Nanopartículas Metálicas , Paládio , Pontos Quânticos , Ouro/química , Aflatoxina B1/análise , Paládio/química , Nanopartículas Metálicas/química , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Técnicas Biossensoriais/métodos , Carbono/química , Pontos Quânticos/química , Hibridização de Ácido Nucleico , Vinho/análise , DNA/química , Transferência Ressonante de Energia de Fluorescência/métodos , Arachis/química , Sequências Repetidas InvertidasRESUMO
STUDY OBJECTIVE: To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and symptomatic lymphocele after laparoscopic pelvic lymphadenectomy. DESIGN: Retrospective analysis. SETTING: Single-center academic hospital. PATIENTS: In total, 217 patients with gynecological malignancies were included. INTERVENTIONS: Patients were classified into two groups: group 1 (vascular clips were used to seal the targeted lymphatics) and group 2 (electrothermal instruments were used to seal the targeted lymphatics). The patients were followed up 4-6 weeks after surgery to evaluate the incidence of lymphoceles by ultrasound or CT. Symptomatic lymphoceles are defined as those that cause infection, deep vein thrombosis with or without swelling of the extremities, edema (swelling) of the extremities or perineum, hydronephrosis, and/or moderate to severe pain. MEASUREMENTS AND MAIN RESULTS: One hundred and thirteen patients were enrolled in group 1, and 104 patients were enrolled in group 2. Lymphoceles were observed in 46 (21.2%) patients. Fewer lymphoceles occurred in group 1 than in group 2 (8 [7.1%] vs. 38 [36.5%], p <.001). The percentage of significantly sized lymphoceles was lower in group 1 than that in group 2 (4 [3.5%] vs. 30 [28.8%], p <.001]. Symptomatic lymphoceles occurred in 18 patients (8.3%), and only one (1.0%) occurred in group 1, while 17 (16.3%) occurred in group 2 (p <.001). A multivariate analysis revealed that vascular clips were the only independent factor for preventing lymphocele (OR = 7.65, 95% CI = [3.30-17.13], p <.001) and symptomatic lymphocele (OR = 22.03, 95% CI = [2.84-170.63], p = .003). CONCLUSION: The results indicate that the use of vascular clips may be useful for the prevention of the development of lymphocele and symptomatic lymphocele secondary to pelvic lymphadenectomy performed via laparoscopy.
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Chiral superstructures with unique chiroptical properties that are not inherent in the individual units are essential in applications such as 3D displays, spintronic devices, biomedical sensors, and beyond. Generally, chiral superstructures are obtained by tedious procedures exploring various physical and chemical forces to break spatial symmetry during the self-assembly of discrete nanoparticles. In contrast, we herein present a simple and efficient approach to chiral superstructures by intercalating small chiral molecules into preformed achiral superstructures. As a model system, the chiral CdSe nanoplatelet (NPL) superlattice exhibits a giant and tunable optical activity with the highest g-factor reaching 3.09 × 10-2 to the excitonic transition of the NPL superlattice, nearly 2 orders of magnitude higher than that of the corresponding separated chiral NPLs. The theoretical analysis reveals that the chiral deformation in the NPL superlattice induced by the chiral perturbation of the small chiral molecules is critical to the observed huge optical activity. We anticipate that this research lays a foundation for understanding and applying chiral inorganic nanosystems.
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Pheochromocytoma/paraganglioma (PGPG) is a rare neuroendocrine tumor. Amino acid metabolism is crucial for energy production, redox balance, and metabolic pathways in tumor cell proliferation. This study aimed to build a risk model using amino acid metabolism-related genes, enhancing PGPG diagnosis and treatment decisions. We analyzed RNA-sequencing data from the PCPG cohort in the GEO dataset as our training set and validated our findings using the TCGA dataset and an additional clinical cohort. WGCNA and LASSO were utilized to identify hub genes and develop risk prediction models. The single-sample gene set enrichment analysis, MCPCOUNTER, and ESTIMATE algorithm calculated the relationship between amino acid metabolism and immune cell infiltration in PCPG. The TIDE algorithm predicted the immunotherapy efficacy for PCPG patients. The analysis identified 292 genes with differential expression, which are involved in amino acid metabolism and immune pathways. Six genes (DDC, SYT11, GCLM, PSMB7, TYRO3, AGMAT) were identified as crucial for the risk prediction model. Patients with a high-risk profile demonstrated reduced immune infiltration but potentially higher benefits from immunotherapy. Notably, DDC and SYT11 showed strong diagnostic and prognostic potential. Validation through quantitative Real-Time Polymerase Chain Reaction and immunohistochemistry confirmed their differential expression, underscoring their significance in PCPG diagnosis and in predicting immunotherapy response. This study's integration of amino acid metabolism-related genes into a risk prediction model offers critical clinical insights for PCPG risk stratification, potential immunotherapy responses, drug development, and treatment planning, marking a significant step forward in the management of this complex condition.
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Tamoxifen is the frontline therapeutic agent for the estrogen receptor-positive (ER + ) subtype of breast cancer patients, which accounts for 70-80% of total breast cancer incidents. However, clinical resistance to tamoxifen has become increasingly common, highlighting the need to identify the underlying cellular mechanisms. In our study, we employed a genome-scale CRISPR-Cas9 loss-of-function screen and validation experiments to discover that Tafazzin (TAZ), a mitochondrial transacylase, is crucial for maintaining the cellular sensitivity of ER+ breast cancer cells to tamoxifen and other chemotherapies. Mechanistically, we found that cardiolipin, whose synthesis and maturation rely on TAZ, is required to maintain cellular sensitivity to tamoxifen. Loss of metabolic enzymatic activity of TAZ causes ERα downregulation and therapy resistance. Interestingly, we observed that TAZ deficiency also led to the upregulation of lysophosphatidylcholine (LPC), which in turn suppressed ERα expression and nuclear localization, thereby contributing to tamoxifen resistance. LPC is further metabolized to lysophosphatidic acid (LPA), a bioactive molecule that supports cell survival. Thus, our findings suggest that the depletion of TAZ promotes tamoxifen resistance through an LPC-LPA phospholipid synthesis axis, and targeting this lipid metabolic pathway could restore cell susceptibility to tamoxifen treatment.
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Neoplasias da Mama , Tamoxifeno , Humanos , Feminino , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Fosfolipídeos/uso terapêutico , Transdução de Sinais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Background: Transformation of endometriosis to malignancy is a rare occurrence. Clear cell ovarian cancer and endometrioid ovarian cancer are the two histotypes most consistently linked to endometriosis. The exact pathways leading to malignant transformation of endometriosis remain elusive. Case presentation: A 41-year-old woman presented to our hospital with a ten days history of abdominal pain which was not responsive to medication. Pathological examination revealed an unexpected finding of bilateral endometriosis associated with distinct malignancies: a clear cell carcinoma in the right ovary and a well-differentiated endometrioid carcinoma in the left ovary. Molecular analysis indicated a shared somatic driver mutation in ING1 in the eutopic endometrium and the bilateral ovaries while simultaneously exhibiting specific genetic alterations unique to each carcinoma. Notably, several common mutation sites were also identified, including previously reported common oncogenes (KRAS, PIK3CA, ARID1A). This finding prompts the hypothesis of a possible monoclonal origin of the two tumours. Conclusion: This case represents an exceedingly rare occurrence of two different histotypes of ovarian endometriosis-associated cancer manifesting simultaneously in bilateral ovaries. Based on genetic analysis, we hypothesize that these malignancies may have a monoclonal origin, providing insights into understanding the different biological mechanisms underlying carcinogenesis.
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Clean energy is urgently needed to realize mining projects' sustainable development (SD). This study aims to discuss the clean energy development path and the related issues of SD in the ecological environment driven by big data for mining projects. This study adopts a comprehensive research approach, including a literature review, case analysis, and model construction. Firstly, an in-depth literature review of the development status of clean energy is carried out, and the existing research results and technology applications are explored. Secondly, some typical mining projects are selected as cases to discuss the practice and effect of their clean energy application. Finally, the corresponding clean energy development path and the SD analysis model of the ecological environment are constructed based on big data technology to evaluate the feasibility and potential benefits of promoting and applying clean energy in mining projects. (1) It is observed that under different Gross Domestic Product (GDP) growth rates, the new and cumulative installed capacities of wind energy show an increasing trend. In 2022, under the low GDP growth rate, the cumulative installed capacity of global wind energy was 370.60 Gigawatt (GW), and the new installed capacity was 45 GW. With the high GDP growth rate, the cumulative and new installed capacities were 367.83 GW and 46 GW. As the economy grows, new wind energy capacity is expected to increase significantly by 2030. In 2046, 2047, and 2050, carbon dioxide (CO2) emissions reductions are projected to be 8183.35, 8539.22, and 9842.73 Million tons (Mt) (low scenario), 8750.68, 9087.16, and 10,468.75 Mt (medium scenario), and 9083.03, 9458.86, and 10,879.58 Mt (high scenario). By 2060, it is expected that CO2 emissions reduction will continue to increase. (2) The proposed clean energy development path model has achieved a good effect. Through this study, it is hoped to provide empirical support and decision-making reference for the development of mining projects in clean energy, and promote the SD of the mining industry, thus achieving a win-win situation of economic and ecological benefits. This is of great significance for protecting the ecological environment and realizing the sustainable utilization of resources.
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Dióxido de Carbono , Desenvolvimento Sustentável , Big Data , Mineração , Desenvolvimento Econômico , Energia RenovávelRESUMO
Two-photon absorption (TPA) fluorescence imaging holds great promise in diagnostics and biomedicine owing to its unparalleled spatiotemporal resolution. However, the adaptability and applicability of currently available TPA probes, which act as a critical element for determining the imaging contrast effect, is severely challenged by limited photo-luminescence in vivo. This is particularly a result of uncontrollable aggregation that causes fluorescence quenching, and inevitable photo-oxidation in harsh physiological milieu, which normally leads to bleaching of the dye. Herein, we describe the remarkably enhanced TPA fluorescence imaging capacity of self-assembling near-infrared (NIR) cyanine dye-based nanoprobes (NPs), which can be explained by a photo-oxidation enhanced emission mechanism. Singlet oxygen generated during photo-oxidation enables chromophore dimerization to form TPA intermediates responsible for enhanced TPA fluorescence emission. The resulting NPs possess uniform size distribution, excellent stability, more favorable TPA cross-section and anti-bleaching ability than a popular TPA probe rhodamine B (RhB). These properties of cyanine dye-based TPA NPs promote their applications in visualizing blood circulation and tumoral accumulation in real-time, even to cellular imaging in vivo. The photo-oxidation enhanced emission mechanism observed in these near-infrared cyanine dye-based nanoaggregates opens an avenue for design and development of more advanced TPA fluorescence probes.
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Ácido Hipocloroso , Quinolinas , Oxirredução , Dimerização , Luminescência , Imagem Óptica , Compostos de SódioRESUMO
BACKGROUND/AIM: Although previous studies have revealed the influence of the mandibular third molar (M3) on mandibular condylar fracture risk and that the presence of M3 could result in different incidences of condylar and angle fractures, there have been no analyses of the influence of M3 on fracture patterns. Moreover, evaluations of M3 position using panoramic radiography have shown insufficient accuracy. This study investigated the relationship between condylar fracture patterns and M3 position using panoramic radiography and computed tomography. MATERIALS AND METHODS: This retrospective study included 280 patients with unilateral mandibular condylar fractures and ipsilateral M3 admitted to West China Hospital of Stomatology between January 2016 and June 2022. Patient medical records, panoramic radiographs, and computed tomography images were collected. The vertical and horizontal positions of M3 were classified using the Pell and Gregory system. M3 angulation was defined as the angle between the long axis of M3 and the mandibular occlusal plane. Condylar fracture patterns were classified as intracapsular (Types A-C) or extracapsular (neck and base). Data were analyzed using McNemar-Bowker test, Pearson chi-squared test, and Fisher's exact test. RESULTS: Classification of M3 position differed significantly between panoramic radiography and computed tomography images (p < .05). There was a significant association between the mandibular condylar fracture pattern and M3 horizontal position on computed tomography (p < .05). Class I M3 position on computed tomography was associated with a higher incidence of intracapsular than extracapsular fractures, along with a higher incidence of Type B than base fractures; the opposite relationships were observed for Class II. No such association was identified on panoramic radiography. CONCLUSIONS: Mandibular condylar fracture patterns were presumably influenced by M3 horizontal position on computed tomography. The imaging modality affected the classification of M3 position and subsequent analyses. Computed tomography is recommended for future studies to improve accuracy and reliability.
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Fraturas Mandibulares , Dente Impactado , Humanos , Estudos Retrospectivos , Radiografia Panorâmica , Dente Serotino/diagnóstico por imagem , Reprodutibilidade dos Testes , Dente Impactado/diagnóstico por imagem , Côndilo Mandibular/diagnóstico por imagem , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has attracted great attention for its ability to up-regulate innate immune response and thus enhance cancer immunotherapy. However, many STING agonists limit the further advancement of immunotherapy due to weak tumor responsiveness or low activation efficiency. The responsive and effective activation of cGAS-STING signaling in tumors is a highly challenging process. METHODS: In this study, a manganese-based nanoplatform (MPCZ NPs) was constructed that could responsively and efficiently generate more manganese ions (Mn2+) and reactive oxygen species (ROS) to activate cGAS-STING signaling pathway. Briefly, manganese dioxide (MnO2) was loaded with zinc protoporphyrin IX (ZPP) molecule and coated by polydopamine (PDA) embedded with NH4HCO3 to obtain MPCZ NPs. Additionally, MPCZ NPs were evaluated in vitro and in vivo for their antitumor effects by methyl thiazolyl tetrazolium (MTT) assay and TUNEL assays, respectively. RESULTS: In this system, tumor responsiveness was achieved by exogenous (laser irradiation) and endogenous (high levels GSH) stimulation, which triggered the collapse or degradation of PDA and MnO2. Moreover, the release of Mn2+ augmented the cGAS-STING signaling pathway and enhanced the conversion of hydrogen peroxide (H2O2) to hydroxyl radical (·OH) under NIR laser irradiation. Furthermore, the release of ZPP and the elimination of GSH by MPCZ NPs inhibited HO-1 activity and prevented ROS consumption, respectively. CONCLUSIONS: This adopted open source and reduce expenditure strategy to effectively generate more ROS and Mn2+ to responsively activate cGAS-STING signaling pathway, providing a new strategy for improving immunotherapy.
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It is a challenge to design photosensitizers to balance between the tumor-targeting enrichment for precise treatment and efficient clearance within a reasonable timescale for reducing side effects. Herein, an ultra-small nano-photosensitizer 1a with excellent tumor-specific accumulation and renal clearance is reported. It is formed from the self-assembly of compound 1 bearing three triethylene glycol (TEG) arms and two pyridinium groups in water. The positively charged surface with neutral TEG coating enables 1a to efficiently target the tumor, with the signal-to-background ratio reaching as high as 11.5 after tail intravenous injection. The ultra-small size of 1a with an average diameter of 5.6 nm allows its fast clearance through kidney. Self-assembly also endows 1a with an 18.2-fold enhancement of reactive oxygygen species generation rate compared to compound 1 in organic solution. Nano-PS 1a manifests an excellent photodynamic therapy efficacy on tumor-bearing mouse models. This work provides a promising design strategy of photosensitizers with renal clearable and tumor-targeting ability.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Medicina de Precisão , Linhagem Celular Tumoral , Neoplasias/terapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Nanomedicina TeranósticaRESUMO
Chromoproteins are a class of delicate natural compounds that elegantly complex photosensitive species with proteins and play a central role in important life processes, such as photosynthesis. Inspired by chromoproteins, researchers integrate simple peptides and photosensitive molecular motifs to generate chromopeptides. Compared with chromoproteins, chromopeptides exhibit a relatively simple molecular structure, flexible and adjustable photophysical properties, and a capability of programmable self-assembly. Chromopeptide self-assembly has attracted great attention as the resultant high-level architectures exhibit an ingenious combination of photofunctions and biofunctions. This review systematically summarizes recent advances in chromopeptide nanoarchitectonics with particular focus on the design strategy, assembly mechanism, and structure-function relationship. Among them, the effect of peptide sequences and the variation in photophysical performance are critically emphasized. On this basis, various applications, including biomedicine and artificial photosynthesis, are discussed together with the future prospects of chromopeptide nanoarchitectonics. This review will provide insights into chromopeptide nanoarchitectonics and corresponding materials with precise designs, flexible nanostructures and versatile functions. In addition, knowledge involving chromopeptide nanoarchitectonics may aid in the development of many other kinds of supramolecular biological materials and bioengineering techniques.
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Nanoestruturas , Peptídeos , Peptídeos/química , Proteínas , Nanoestruturas/química , Estrutura Molecular , Sequência de AminoácidosRESUMO
BACKGROUND: Endometrial cancer (EC) with metastasis in pelvic/para-aortic lymph nodes suggests an unsatisfactory prognosis. Nevertheless, there is still rare literature focusing on the role of epithelial-mesenchymal transition (EMT) in lymph node metastasis (LNM) in EC. METHODS: Transcriptional data were derived from the TCGA database. Patients with stage IA-IIIC2 EC were included, constituting the LN-positive and LN-negative groups. To evaluate the extent of EMT, an EMT signature composed of 315 genes was adopted. The EMT-related genes (ERGs) were obtained from the dbEMT2 database, and the differentially expressed ERGs (DEERGs) between these two groups were screened. On the basis of DEERGs, pathway analysis was carried out. We eventually adopted the logistic regression model to build an ERG-based gene signature with predictive value for LNM in EC. RESULTS: A total of 498 patients were included, with 75 in the LN-positive group. Median EMT score of tumor tissues from LN-negative group was - 0.369, while that from the LN-positive group was - 0.296 (P < 0.001), which clearly exhibited a more mesenchymal phenotype for LNM cases on the EMT continuum. By comparing expression profiles, 266 genes were identified as DEERGs, in which 184 were upregulated and 82 were downregulated. In pathway analysis, various EMT-related pathways were enriched. DEERGs shared between molecular subtypes were comparatively few. The ROC curve and logistic regression analysis screened 7 genes with the best performance to distinguish between the LN-positive and LN-negative group, i.e., CIRBP, DDR1, F2RL2, HOXA10, PPARGC1A, SEMA3E, and TGFB1. A logistic regression model including the 7-gene-based risk score, age, grade, myometrial invasion, and histological subtype was built, with an AUC of 0.850 and a favorite calibration (P = 0.074). In the validation dataset composed of 83 EC patients, the model exhibited a satisfactory predictive value and was well-calibrated (P = 0.42). CONCLUSION: The EMT status and expression of ERGs varied in LNM and non-LNM EC tissues, involving multiple EMT-related signaling pathways. Aside from that, the distribution of DEERGs differed among molecular subtypes. An ERG-based gene signature including 7 DEERGs exhibited a desirable predictive value for LNM in EC, which required further validation based upon clinical specimens in the future.
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Neoplasias do Endométrio , Transição Epitelial-Mesenquimal , Humanos , Feminino , Metástase Linfática/patologia , Neoplasias do Endométrio/patologia , Linfonodos/patologia , Excisão de Linfonodo , Proteínas de Ligação a RNARESUMO
Based on DNA strand replacement reaction and aptamer-specific recognition, a simple dual-labeled DNA nanostructure is designed for the simultaneous detection of Ochratoxin A (OTA) and aflatoxin B1 (AFB1). C1 is labeled with Cy3 and Cy5, while C2 and C3 are labeled with BHQ2. The fluorescence intensity of DNA nanostructure composed of C1, C2 and C3 is weak because of fluorescence resonance energy transfer. When OTA Aptamer (OTA-Apt) and AFB1 Aptamer (AFB1-Apt) are added to the homogeneous system at the same time, C1 can be replaced with the help of toehold strand displacement, resulting in fluorescence enhancement. In the presence of both OTA and AFB1, the toehold strand displacement reaction is inhibited due to preferential binding between the target and their corresponding aptamers. The limit of detection of OTA was 0.007 ng/mL and that of AFB1 was 0.03 ng/mL. The recoveries of OTA and AFB1 were 96%-101% and 97%-101% in the corn sample, and 99%-101% and 92%-106% in the wine sample. Compared with other sensors, the preparation of this aptasensor needs simpler experimental steps and a shorter total-preparing time, confirming the convenient, rapid, and time-saving operation process.
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Nanoestruturas , Aflatoxina B1/química , DNA/química , Corantes Fluorescentes/química , Limite de DetecçãoRESUMO
Ovarian cancer (OC) is characterised by heterogeneity that complicates the prediction of patient survival and treatment outcomes. Here, we conducted analyses to predict the prognosis of patients from the Genomic Data Commons database and validated the predictions by fivefold cross-validation and by using an independent dataset in the International Cancer Genome Consortium database. We analysed the somatic DNA mutation, mRNA expression, DNA methylation, and microRNA expression data of 1203 samples from 599 serous ovarian cancer (SOC) patients. We found that principal component transformation (PCT) improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than the decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. Our study provides perspective on building reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC.Impact statementWhat is already known on this subject? Recent studies have focussed on predicting cancer outcomes based on omics data. But the limitation is the performance of single-platform genomic analyses or the small numbers of genomic analyses.What do the results of this study add? We analysed multi-omics data, found that principal component transformation (PCT) significantly improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than did decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes.What are the implications of these findings for clinical practice and/or further research? Our study provides perspective on how to build reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC for future studies.
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Multiômica , Neoplasias Ovarianas , Humanos , Feminino , Perfilação da Expressão Gênica , Prognóstico , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/genéticaRESUMO
As a new type of inorganic-organic hybrid semiconductor, quantum-confined atomically precise metal nanoclusters (MNCs) have been widely applied in the fields of chemical sensing, optical imaging, biomedicine and catalysis. Herein, we successfully design and fabricate the first example of MNC-based spin valves (SVs) that exhibit remarkable magnetoresistance (MR) value up to 1.6 % even at room temperature (300â K). The concomitant photoresponse of MNC-based SVs unambiguously confirms that the spin-polarized electron transmission takes place across the MNC interlayer. Furthermore, the spin-dependent transport property of MNC-based SVs is largely varied by changing the atomic structure of MNCs. Both experimental proofs and quantum chemistry calculations reveal that the atomic structure-discriminative spin transport behavior is attributed to the distinct spin-orbit coupling (SOC) effect of MNCs.