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Silage is an excellent method of feed preservation; however, carbon dioxide, methane and nitrous oxide produced during fermentation are significant sources of agricultural greenhouse gases. Therefore, determining a specific production method is crucial for reducing global warming. The effects of four temperatures (10 °C, 20 °C, 30 °C, and 40 °C) on silage quality, greenhouse gas yield and microbial community composition of forage sorghum were investigated. At 20 °C and 30 °C, the silage has a lower pH value and a higher lactic acid content, resulting in higher silage quality and higher total gas production. In the first five days of ensiling, there was a significant increase in the production of carbon dioxide, methane, and nitrous oxide. After that, the output remained relatively stable, and their production at 20 °C and 30 °C was significantly higher than that at 10 °C and 40 °C. Firmicutes and Proteobacteria were the predominant silage microorganisms at the phylum level. Under the treatment of 20 °C, 30 °C, and 40 °C, Lactobacillus had already dominated on the second day of silage. However, low temperatures under 10 °C slowed down the microbial community succession, allowing, bad microorganisms such as Chryseobacterium, Pantoea and Pseudomonas dominate the fermentation, in the early stage of ensiling, which also resulted in the highest bacterial network complexity. According to random forest and structural equation model analysis, the production of carbon dioxide, methane and nitrous oxide is mainly affected by microorganisms such as Lactobacillus, Klebsiella and Enterobacter, and temperature influences the activity of these microorganisms to mediate gas production in silage. This study helps reveal the relationship between temperature, microbial community and greenhouse gas production during silage fermentation, providing a reference for clean silage fermentation.
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Miniaturization of wireless neural-recording systems enables minimally-invasive surgery and alleviates the rejection reactions for implanted brain-computer interface (BCI) applications. Simultaneous massive-channel recording capability is essential to investigate the behaviors and inter-connections in billions of neurons. In recent years, battery-free techniques based on wireless power transfer (WPT) and backscatter communication have reduced the sizes of neural-recording implants by battery eliminating and antenna sharing. However, the existing battery-free chips realize the multi-channel merging in the signal-acquisition circuits, which leads to large chip area, signal attenuation, insufficient channel number or low bandwidth, etc. In this work, we demonstrate a 2mm×2mm battery-free neural dielet, which merges 128 channels in the wireless part. The neural dielet is fabricated with 65nm CMOS process, and measured results show that: 1) The proposed multi-carrier orthogonal backscatter technique achieves a high data rate of 20.16Mb/s and an energy efficiency of 0.8pJ/bit. 2) A self-calibrated direct digital converter (SC-DDC) is proposed to fit the 128 channels in the 2mm×2mm die, and then the all-digital implementation achieves 0.02mm2 area and 9.87µW power per channel.
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Thyroid cancer is a prevalent endocrine malignancy whose global incidence has risen over the past several decades. Ferroptosis, a regulated form of cell death distinguished by the excessive buildup of iron-dependent lipid peroxidates, stands out from other programmed cell death pathways in terms of morphological and molecular characteristics. Increasing evidence suggests a close association between thyroid cancer and ferroptosis, that is, inducing ferroptosis effectively suppresses the proliferation of thyroid cancer cells and impede tumor advancement. Therefore, ferroptosis represents a promising therapeutic target for the clinical management of thyroid cancer in clinical settings. Alterations in ferroptosis-related genes hold potential for prognostic prediction in thyroid cancer. This review summarizes current studies on the role of ferroptosis in thyroid cancer, elucidating its mechanisms, therapeutic targets, and predictive biomarkers. The findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of innovative treatment strategies and accurate predictors for the thyroid cancer.
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Biomarcadores Tumorais , Ferroptose , Neoplasias da Glândula Tireoide , Humanos , Ferroptose/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Animais , Terapia de Alvo Molecular , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , PrognósticoRESUMO
Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.
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Células Matadoras Naturais , Receptores de Antígenos Quiméricos , Receptores da Tireotropina , Neoplasias da Glândula Tireoide , Receptores da Tireotropina/imunologia , Receptores da Tireotropina/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/imunologia , Humanos , Animais , Células Matadoras Naturais/imunologia , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Camundongos , Diferenciação Celular , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos NOD , Proliferação de Células , Citotoxicidade Imunológica , Imunoterapia Adotiva/métodosRESUMO
BACKGROUND: Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics. MATERIALS AND METHODS: The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system. RESULTS: The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively. CONCLUSION: This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Proteômica , Carcinoma Papilar/cirurgia , Aprendizado de Máquina , Medição de Risco , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Thyroid cancer can be divided into two types according to its cellular origin, i.e., malignant tumors originating from thyroid cells and cancers that metastasize to the thyroid from other sites, the latter of which are, clinically rare. This article reports the diagnosis and treatment of a rectal neuroendocrine neoplasm metastasis to the thyroid. No similar cases have been reported before. This case suggests that when evaluating thyroid tumors, clinicians should not only carefully identify the clinical features of the tumor but also pay special attention to the patient's history of tumors, especially neuroendocrine neoplasms. For definite secondary thyroid malignancies, neck surgery is feasible if the thyroid is the only site of metastasis; otherwise, the subsequent diagnosis and treatment plan should be determined after a comprehensive evaluation of the primary tumor and patient's general condition.
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BACKGROUND: The incidence of Langerhans cell histiocytosis (LCH) is low, and involvement of the thyroid is even rarer, which results in high missed diagnosis or misdiagnosis rates. CASE SUMMARY: We report a young woman with a thyroid nodule. Thyroid malignancy was suggested by fine needle aspiration, but she was eventually diagnosed with multisystem LCH, thus avoiding thyroidectomy. CONCLUSION: The clinical manifestations of LCH involving the thyroid are atypical, and the diagnosis depends on pathology. Surgery is the main method for treating primary thyroid LCH, while chemotherapy is the main treatment method for multisystem LCH.
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The triple-negative breast cancer (TNBC) subtype is the most aggressive type of breast cancer with a low survival prognosis and high recurrence rate. There is currently no effective treatment to improve it. In this work, we explored the effect of a synthetic compound named WXJ-103 on several aspects of TNBC biology. The human breast cancer cell lines MDA-MB-231 and MCF-7 were used in the experiments, and the cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and the cell migration and invasion abilities were detected by wound healing assay and Transwell invasion assay. Cell cycle and apoptosis experiments were analyzed by flow cytometry, and protein levels related to cyclin-dependent kinase (CDK) 4/6-cyclin D-Rb-E2F pathway were analyzed by western blotting. Then, in-vivo experiments were performed to determine the clinical significance and functional role of WXJ-103. The results show that WXJ-103 can inhibit the adhesion, proliferation, migration, and invasion of TNBC cells, and can arrest the cell cycle in G1 phase. The levels of CDK4/6-cyclin D-Rb-E2F pathway-related proteins such as CDK6 and pRb decreased in a dose-dependent manner. Therefore, the antitumor activity of WXJ-103 may depend on the inhibition of CDK4/6-cyclin D1-Rb-E2F pathway. This research shows that WXJ-103 may be a new promising antitumor drug, which can play an antitumor effect on TNBC and provide new ideas for the treatment of TNBC.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Proliferação de Células , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/uso terapêutico , Purinas/farmacologia , Linhagem Celular TumoralRESUMO
BCR-ABL1 kinase is a key driver of the pathophysiology of chronic myeloid leukemia (CML). Current treatments need to broaden the chemical diversity of BCR-ABL1 kinase inhibitors to overcome drug resistance. We designed and synthesized a series of aromatic amide derivatives based on several generations of BCR-ABL1 kinase inhibitors. Biological studies showed that compared with Imatinib, these compounds showed significant proliferation inhibitory activities of HL-60 and K562 in cell activity assay. Compounds 4g and 4j exhibited significant anti-tumor activity against the K562 cells with IC50 values of 6.03 ± 0.49 µM and 5.66 ± 2.06 µM respectively. Compounds 4g and 4j, as potential BCR-ABL1 inhibitors, inhibit the phosphorylation of ABL1 and CRKL in a dose-dependent manner. Therefore, compounds 4g and 4j can be used as a starting point for further optimization.
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Amidas , Proteínas de Fusão bcr-abl , Humanos , Amidas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/farmacologia , Mesilato de Imatinib/farmacologia , Células K562 , ApoptoseRESUMO
Metal sulfides are regarded as efficient scavengers for heavy metals. However, the heavy metal adsorption capacity of metal sulfides is far from its theoretical values due to the insufficient exposure of adsorption sites. Surface modification of metal sulfides is considered one of the most effective strategies for improving heavy metal removal performance. Here, microalgae-derived carbon quantum dots (CQDs) were used as a green modifier for mediating nano-MnS/FeS formation to enhance Cd2+ removal. With the addition of 1 wt% CQDs, the Cd2+ adsorption capacity of 1 %CQDs-MnS reached 481 mg/g at 25 °C and 648.6 mg/g at 45 °C, which surpassed most of the previously reported metal sulfides. Furthermore, the CQDs-modified MnS displayed a better Cd2+ removal capacity than the commercial modifier sodium alginate. The mechanism analysis suggested that decreasing the particle size to expose more adsorption sites and providing additional chelating sites derived from the CQDs are two main reasons why CQDs enhance the Cd2+ adsorption capacity of metal sulfides. This study presents an exceptional cadmium nano-adsorbent of 1 %CQDs-MnS and provides a new perspective on the enhancement of heavy metal removal by using CQDs as a promising and universal green modifier that mediates the formation of metal sulfides.
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Metais Pesados , Microalgas , Pontos Quânticos , Cádmio , Carbono , Adsorção , Alginatos , SulfetosRESUMO
Objectives: To explore the preoperative high-risk clinical factors for contralateral medium-volume central lymph node metastasis (conMVCLNM) in unilateral papillary thyroid carcinoma (uPTC) and the indications for dissection of contralateral central lymph nodes (conCLN). Methods: Clinical and pathological data of 204 uPTC patients who underwent thyroid surgery at the Hangzhou First People's Hospital from September 2010 to October 2022 were collected. Univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors for contralateral central lymph node metastasis (conCLNM) and conMVCLNM in uPTC patients based on the preoperative clinical data. Predictive models for conCLNM and conMVCLNM were constructed using logistic regression analyses and validated using receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: Univariate and multivariate logistic regression analyses showed that gender (P < 0.001), age (P < 0.001), tumor diameter (P < 0.001), and multifocality (P = 0.008) were independent risk factors for conCLNM in uPTC patients. Gender(P= 0.026), age (P = 0.010), platelet-to-lymphocyte ratio (PLR) (P =0.003), and tumor diameter (P = 0.036) were independent risk factors for conMVCLNM in uPTC patients. A predictive model was established to assess the risk of conCLNM and conMVCLNM, with ROC curve areas of 0.836 and 0.845, respectively. The C-index, the calibration curve, and DCA demonstrated that the model had good diagnostic value. Conclusion: Gender, age, tumor diameter, and multifocality are high-risk factors for conCLNM in uPTC patients. Gender, age, tumor diameter, and PLR are high-risk factors for conMVCLNM in uPTC patients, and preventive conCLN dissection should be performed.
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Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Nomogramas , Metástase Linfática/patologia , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
PURPOSE: Grb2 associated binding protein 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction which involved in several pathological process. However, the role of Gab1 in pressure overload-induced ventricular arrhythmias (VAs) remain poorly understood. In the current study, we aimed to test the role of Gab1 in VA susceptibility induced by pressure overload. METHODS: We overexpressed Gab1 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. Aortic banding (AB) surgery was performed in C57BL6/J mice to induce heart failure (HF). Four weeks following AB, histology, echocardiography, and biochemical analysis were conducted to investigate cardiac structural remodeling and electrophysiological studies were performed to check the electrical remodeling. Western blot analysis was used to explore the underlying mechanisms. RESULTS: The mRNA and protein expression were downregulated in AB hearts compared to sham hearts. Gab1 overexpression significantly reversed AB-induced cardiac structural remodeling including ameliorated AB-induced cardiac dysfunction, cardiac fibrosis, and inflammatory response. Moreover, Gab1 overexpression also markedly alleviated AB-induced electrical remodeling including ion channel alterations and VA susceptibility. Mechanistically, we found that TLR4/MyD88/NF-κB contributes to the cardio protective effect of Gab1 overexpression on AB-induced VAs. CONCLUSIONS: Our study manifested that Gab1 may serve as a promising anti-arrhythmic target via inhibiting TLR4/MyD88/NF-κB signaling pathway induced by AB.
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The 2013 "Qingdao oil pipeline explosion" contaminated about 2.5 km of shoreline in the Jiaozhou Bay area and aroused widespread concern because of the serious casualties even though it was not the most severe oil-spill contamination in China. To evaluate the long-term impact, we collected thirty-three surface sediment samples after 3 years of the accident, with sixteen polycyclic aromatic hydrocarbons (PAHs) detected. Spatial-temporal variation in PAHs revealed that a minimal impact might still be present after 3 years. Source analysis combined with a one-way ANOVA showed that pyrolytic sources were consistently predominant. The environmental impact was already minimal 3 years later and negligible thereafter. Although the cancer risk has decreased over the years, there has always been a potential hazard to human for specific occupation, with all of the risk values exceeded 10-6. This study offers a reference for assessing the long-term impact of oil spills in similar bay areas.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Acidentes , China , Monitoramento Ambiental , Explosões , Sedimentos Geológicos/análise , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análiseRESUMO
Macrophages originating from the yolk sac or bone marrow play essential roles in tissue homeostasis and disease. Bone marrow-derived monocytes differentiate into Ly6Chi and Ly6Clo macrophages according to the differential expression of the surface marker protein Ly6C. Ly6Chi and Ly6Clo cells possess diverse functions and transcriptional profiles and can accelerate the disease process or support tissue repair and reconstruction. In this review, we discuss the basic biology of Ly6Chi and Ly6Clo macrophages, including their origin, differentiation, and phenotypic switching, and the diverse functions of Ly6Chi and Ly6Clo macrophages in homeostasis and disease, including in injury, chronic inflammation, wound repair, autoimmune disease, and cancer. Furthermore, we clarify the differences between Ly6Chi and Ly6Clo macrophages and their connections with traditional M1 and M2 macrophages. We also summarize the limitations and perspectives for Ly6Chi and Ly6Clo macrophages. Overall, continued efforts to understand these cells may provide therapeutic approaches for disease treatment.
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Macrófagos , Monócitos , Humanos , Inflamação/metabolismo , Contagem de Leucócitos , CicatrizaçãoRESUMO
Long noncoding RNAs (lncRNAs) play a significant role in cancer biology. This study aimed to determine the roles of lncRNAs in establishing the differences in clinical features between patients with papillary thyroid carcinoma (PTC) without Hashimoto's thyroiditis (HT) and patients with PTC and HT. In the present study, we detected the differentially expressed lncRNAs between tumor tissues of patients with PTC with or without HT through lncRNA microarrays. The data were verified and analyzed through qRT-PCR, cell viability, cell cycle and bioinformatics analyses. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 5 tissue samples of PTC complicated with HT [PTC/HT (+)] compared with 5 samples of PTC without HT [PTC/HT (-)]. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, particularly immune system processes, were induced in the PTC/HT (+) tissues. Twenty lncRNAs were verified in 31 PTC/HT (+) and 64 PTC/HT (-) specimens by qRT-PCR, and the results were consistent with the microarray data. Specifically, ENST00000452578, a downregulated lncRNA in PTC/HT(+), was negatively correlated with the tumor size. Cell viability assays revealed that ENST00000452578 could inhibit cell proliferation. Our results indicate that lncRNAs and mRNAs play an important role in establishing the different clinical characteristics between patients with PTC/HT(+) and patients with PTC/HT(-), and might provide new insights from the perspective of RNA for obtaining a further understanding of the clinical features related to PTC with HT.
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Objective: Our goal was to investigate the correlation between papillary thyroid carcinoma (PTC) characteristics on ultrasonography and metastases of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN). There is still no good method for clinicians to judge whether a patient needs LN-prRLN resection before surgery, and we also wanted to establish a new scoring system to determine whether patients with papillary thyroid carcinoma require LN-prRLN resection before surgery. Patients and Methods: There were 482 patients with right or bilateral PTC who underwent thyroid gland resection from December 2015 to December 2017 recruited as study subjects. The relationship between the PTC characteristics on ultrasonography and the metastases of LN-prRLN was analyzed by univariate and logistic regression analyses. Based on the risk factors identified in univariate and logistic regression analysis, a nomogram-based LN-prRLN prediction model was established. Result: LN-prRLN were removed from all patients, of which 79 had LN-prRLN metastasis, with a metastasis rate of 16.39%. Multivariate logistic regression analysis revealed that LN-prRLN metastasis was closely related to sex, age, blood supply, larger tumors (> 1 cm) and capsular invasion. A risk prediction model has been established and fully verified. The calibration curve used to evaluate the nomogram shows that the consistency index was 0.75 ± 0.065. Conclusion: Preoperative clinical data, such as sex, age, abundant blood supply, larger tumor (> 1 cm) and capsular invasion, are positively correlated with LN-prRLN metastasis. Our scoring system can help surgeons non-invasively determine which patients should undergo LN-prRLN resection before surgery. We recommend that LN-prRLN resection should be performed when the score is above 103.1.
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Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Nervo Laríngeo Recorrente/diagnóstico por imagem , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Prognóstico , Nervo Laríngeo Recorrente/patologia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , UltrassonografiaRESUMO
Recent studies suggested that dysregulated YY1 plays a pivotal role in many liver diseases. To obtain a detailed view of genes and pathways regulated by YY1 in the liver, we carried out RNA sequencing in HepG2 cells after YY1 knockdown. A rigid set of 2,081 differentially expressed genes was identified by comparing the YY1-knockdown samples (n = 8) with the control samples (n = 14). YY1 knockdown significantly decreased the expression of several key transcription factors and their coactivators in lipid metabolism. This is illustrated by YY1 regulating PPARA expression through binding to its promoter and enhancer regions. Our study further suggest that down-regulation of the key transcription factors together with YY1 knockdown significantly decreased the cooperation between YY1 and these transcription factors at various regulatory regions, which are important in regulating the expression of genes in hepatic lipid metabolism. This was supported by the finding that the expression of SCD and ELOVL6, encoding key enzymes in lipogenesis, were regulated by the cooperation between YY1 and PPARA/RXRA complex over their promoters.
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Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fator de Transcrição YY1/metabolismo , Sequência de Bases , Elongases de Ácidos Graxos , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/fisiologia , PPAR alfa/genética , Regiões Promotoras Genéticas/genética , Receptor X Retinoide alfa , Estearoil-CoA Dessaturase , Fatores de Transcrição/genética , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/fisiologiaRESUMO
The stearoyl-CoA desaturase 1 (SCD1) gene at 10q24.31 encodes the rate limiting enzyme SCD1 that catalyzes the biosynthesis of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). Dysregulated SCD1 activity has been observed in many human diseases including non-alcoholic fatty liver disease (NAFLD), obesity, hypertension, hyperlipidemia, metabolic syndrome and several types of cancer. HNF4A is a central regulator of glucose and lipid metabolism and previous studies suggested that it is deeply involved in regulating the SCD1 activity in the liver. However, the underlying mechanisms on whether and how SCD1 is regulated by HNF4A have not been explored in detail. In this study, we found that HNF4A regulates SCD1 expression by directly binding to the key regulatory regions in the SCD1 locus. Knocking down of HNF4A significantly downregulated the expression of SCD1. Variants rs55710213 and rs56334587 in intron 5 of SCD1 directly reside in a canonical HNF4A binding site. The GG haplotype of rs55710213 and rs56334587 is associated with decreased SCD1 activity by disrupting the binding of HNF4A, which further decreased the enhancer activity and SCD1 expression. In conclusion, our study demonstrated that SCD1 is directly regulated by HNF4A, which may be helpful in the understanding of the altered metabolic pathways in many diseases associated with dysregulated SCD1 or HNF4A or both.
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Regulação Enzimológica da Expressão Gênica , Fator 4 Nuclear de Hepatócito/metabolismo , Polimorfismo de Nucleotídeo Único , Estearoil-CoA Dessaturase/genética , Sítios de Ligação , Elementos Facilitadores Genéticos , Haplótipos , Células Hep G2 , Humanos , Desequilíbrio de Ligação , Motivos de NucleotídeosRESUMO
Axillary lymph node metastasis is a rare event in thyroid carcinoma. The simultaneous expression of carbohydrate antigens 19-9 (CA 19-9) and 242 (CA 242) in thyroid tumors is also extremely rare. Herein, we report a case of axillary lymph node metastasis with elevated serum CA 19-9 and CA 242 in papillary thyroid carcinoma. In a 47-year-old woman with thyroid carcinoma, masses developed in the neck and axilla over a two-month period, which were surgically treated using total thyroidectomy, with neck and axillary lymph node dissection. Histopathological examination confirmed a diffuse sclerosing variant-papillary thyroid carcinoma, with 52 of 63 axillary lymph node metastases. Notably, serum CA 19-9 and CA 242 levels decreased from the initial values of 1,110 and 50 kU/L, respectively, to normal levels one month postoperatively and have remained stable for two years since. The aggressive biological behavior of diffuse sclerosing variant-papillary thyroid carcinoma and the abnormal anatomical distortion caused by tumors in this case most likely reflect the mechanisms underlying retrograde dissemination in lymphatic tubes. However, the mechanism leading to a simultaneous elevation of CA 19-9 and CA 242 secreted by the diffuse sclerosing variant-papillary thyroid carcinoma has not been elucidated. The patient has survived for two years suggesting that timely surgery can help such patients achieve a better prognosis.
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Biogenic phosphorus (P), such as organic P and inorganic pyrophosphates, could substantially contribute towards eutrophication in aquatic systems by internal loading of P from sediment through P species transformation. Previous eutrophication management studies mainly focus on the removal of orthophosphate (Ortho-P), however, an effective approach for biogenic P control from water sources, prior to incorporation in sediment, is still lacking. In this study, a lanthanum/aluminum-hydroxide (LAH) composite was demonstrated to provide both superior removal of Ortho-P and biogenic P, employing myo-inositol hexakisphosphate (IHP) and pyrophosphate (Pyro-P) as model compounds. The maximum IHP and Pyro-P adsorption capacities by LAH attained 36.4 and 21.8 mg P g-1, respectively. In order to understand the mechanisms of adsorption, zeta potential, 31P solid-state nuclear magnetic resonance (NMR) spectroscopy and P K-edge X-ray absorption near edge structure (XANES) techniques were used to characterize the LAH after adsorption. The results supported the hypothesis that the interaction between LAH and P species was through surface adsorption, by the formation of inner-sphere complexes. Linear combination fitting results of XANES data indicated that IHP and Pyro-P preferentially bonded with La-hydroxide in LAH. This study elucidates the adsorption properties and binding mechanisms of IHP and Pyro-P on lanthanum-bearing compounds at the molecular level, indicating that LAH is a promising material for the control of eutrophication.